caprine arthritis encephalitis

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Identity

Preferred Scientific Name

• caprine arthritis encephalitis

International Common Names

• English: CAEV infection; caprine arthritis encephalitis virus infection; caprine arthritis encephalomyelitis; caprine arthritis/encephalitis; caprine arthritis-encephalomyelitis, cae; hard udders in does; leukoencephalomyelitis

English acronym

• CAE

Pathogen/s

Overview

Caprine arthritis-encephalitis virus (CAEV) is lentivirus within the group of small ruminant lentivirus (SRLV) in the family Retroviridae. The SRLV group also includes maedi-visna virus (MVV) [visna maedi virus] and ovine progressive pneumonia virus (OPPV). SRLV infections are life long in sheep and goats and are characterized by periods of latency, followed by recrudescence of virus replication. There are no known therapeutics and no commercially available vaccines. More than 70% of animals demonstrate sub-clinical (non-progressive, NP) disease and 30% of animals have moderate to severe, chronic recurrent (progressive, P) disease. Immunological control of SRLVs is associated with non-progressive status and is likely to be dependent on various factors including SRLV strain pathogenicity and tissue/cell tropisms, immunogenetics, and environmental conditions.

The original characterization of CAEV includes two primary disease manifestations: joint disease (arthritic form) and neurological disease (neurological form). The joint disease form manifests as chronic recurrent arthritis of primarily the carpi (Crawford et al., 1980). Clinically affected goats (progressors) are typically juvenile or adult animals that develop moderate to severe swelling of the bursa of the extensor carpal radialis tendon with variable involvement of the radiocarpal, middle carpal and carpometacarpal joints. Advanced lesions are characterized by marked synovial membrane hyperplasia with diffuse mononuclear cell infiltrates commonly accompanied by soft tissue mineralization and osteolysis. The neurological disease form of CAEV is characterized by leukoencephalomyelitis. It is primarily found in kids of 1-5 months of age and less commonly, adult goats (Cork et al., 1974; O'Sullivan et al., 1978; Norman and Smith, 1983). More recently, the reporting of neurological manifestation of CAEV, MVV and OPPV has declined, which may be a reflection of virus-host adaptation or control measures aimed to reduce neonatal transmission. Other clinical manifestations of CAEV in goats can occur alone or in combination with the primary disease manifestations and include cachexia, weight loss, chronic pneumonia with dyspnoea and mastitis (Phelps and Smith, 1993; Ellis et al., 1988; Cork et al., 1974).

CAEV infection is diagnosed by clinical signs and the detection of serum antibodies. The commonest used serological antibody detection systems include enzyme-linked immunosorbent assays (ELISA) or agar gel immunodiffusion assay (AGID). A recently developed and validated competitive inhibition ELISA for CAEV has shown higher sensitivity than the AGID test (Knowles et al., 1994; Özyörük et al., 2001; Herrmann et al., 2003). However, there is a potential for false negatives and positives using these diagnostic techniques. The number of false negatives depends upon the antigenic similarity of the infecting CAEV strain and the CAEV strain used in the diagnostic test. In addition, false positives may occur due to the presence of passively transferred maternal antibodies in kids less than 1 year of age. Moreover, delayed seroconversion has been reported in sheep and goats infected with SRLV. Given these issues with serological diagnostic tests, there is a need to develop and employ ancillary methods of confirming CAEV infection before death of the animal. Efforts to develop and validate some new tests such as the polymerase chain reaction (PCR) detection of integrated provirus and immunohistochemical detection of viral antigens will be discussed.

The primary mode of transmission of CAEV is through ingestion of colostrum/ milk following birth (Adams et al., 1983), however horizontal transmission between adult goats has been reported (Rowe et al., 1992a). The relative contribution of NP and P goats to transmission of CAEV is not known. However, it is generally believed that both groups of CAEV-infected goats serve as potential reservoirs of CAEV. Therefore, control measures include serological testing of adult goats and separation or elimination of seropositive animals, and heat inactivation of colostrum or milk (56ºC for 1 h) from CAEV-positive nannies.

CAEV and OPPV/MVV have similar modes of transmission. And since genetic information is indicating that CAEV can infect sheep and OPPV/MVV can infect goats under natural conditions, eradication of CAEV will need to include eradication efforts for OPPV/MVV as well.

This disease is on the list of diseases notifiable to the World Organisation for Animal Health (OIE). The distribution section contains data from OIE's WAHID database on disease occurrence. Please see the AHPC library for further information on this disease from OIE, including the International Animal Health Code and the Manual of Standards for Diagnostic Tests and Vaccines. Also see the website: www.oie.int.

Host Animals

Hosts/Species Affected

Caprine arthritis-encephalitis virus (CAEV) transmits between goats mainly through colostrum and milk secretions (Adams et al., 1983; Rowe et al., 1992b). In sheep, maedi-visna virus (MVV) transmits by colostrum/milk and/or respiratory secretions (Sigurdsson et al., 1953; Houwers et al., 1983). Studies focusing on genomic and phylogenetic analysis of small ruminant lentivirus (SRLV) suggested that CAEV can naturally infect sheep and MVV can naturally infect goats (Leroux et al., 1997; Zanoni 1998; Rolland et al., 2002; Shah et al., 2004). CAEV can infect sheep, and MVV can infect goats in an experimental setting (Banks et al., 1983), and lambs can be infected with milk from CAEV-infected does (Oliver et al., 1985). Given similar transmission sources and the results of experimental transmission, it is plausible that CAEV could infect sheep naturally. In naturally infected goats, persistent infections with both CAEV and MVV have been described, and viral chimeras generated by recombination between these variants have been detected (Pisoni et al., 2007; Cruz et al., 2013). In cases where sheep and goats are commonly housed together, a combination of CAEV and MVV/OPP prevention and control methods are advised.

Systems Affected

Distribution

The global distribution of caprine arthritis-encephalitis virus (CAEV) is reported by OIE and is based upon serological and/or virological evidence of CAEV.

CAEV is typically found in countries that routinely serologically test for the virus. Countries that are not listed as having CAEV present do not routinely serologically test for CAEV. In 1984, a global CAEV survey was performed where serum samples came from 112 different locations around the world. At that time, 90% of the positive CAEV AGID tests came from Canada, France, Norway, Switzerland and the USA (Adams et al., 1984). In 2003, these same countries reported the presence but not the percentage of CAEV infection in their goatherds.

Regional seroprevalence studies of CAEV have been performed in the USA and Australia. In 1992, 3790 goats from 28 states in the USA were tested for CAEV using AGID, and 31% tested positive (Cutlip et al., 1992). In Australia in 1995, seroprevalence of CAEV in New South Wales was examined in 1484 goats in 14 dairy herds and 56.8% were CAEV-positive using an ELISA (Greenwood et al., 1995).

For current information on disease incidence, see OIE's WAHID Interface.

Distribution Table

The distribution in this summary table is based on all the information available. When several references are cited, they may give conflicting information on the status. Further details may be available for individual references in the Distribution Table Details section which can be selected by going to Generate Report.

Pathology

Caprine arthritis-encephalitis virus (CAEV) infection results in an immunopathological disease affecting primarily the bursa of the extensor carpal radialis tendon and the radiocarpal, middle carpal and carpometacarpal joints (Cheevers and McGuire, 1988), although involvement of tarsal, stifle, fetlock and atlanto-occipital joints and associated tendon bursa are less commonly affected. Infection with CAEV results in systemic lymphocyte activation and proliferation in lymphoid tissue (lymphoid hyperplasia). CD45R+ CD5- B lymphocytes and IgG-positive plasma cells are the principal mononuclear cell types found in perivascular infiltrates of the radiocarpel joint synovium of progressor goats (Wilkerson et al., 1995a). The titre of antibody to CAEV surface envelope glycoprotein (SU) in the serum and synovial fluid correlates and predicts with the severity of lesions in the radiocarpel joint of CAEV-infected goats (Johnson et al., 1983; Knowles et al., 1990). Moreover, the dominant serum antibody isotype response to SU at the time of seroconversion predicts which goats will become symptomatic progressor goats where a predominance of IgG₁ is found early in CAEV infection in eventual progressor goats and increased anti-SU IgG₂ is found in eventual nonprogressors (Trujillo et al., 2004a). Results suggest that isotype-specific immunoglobulin production to SU may contribute to the pathogenesis of CAEV-induced arthritis.

CAEV replicates in cells of the monocytes/macrophage lineage (Anderson et al., 1983). Using in situ hybridization, CAEV RNA has been identified in cells consistent with macrophage morphology in the brain, spinal cord, lung, joints and mammary gland of naturally CAEV-infected goats (Zink et al., 1990). Others have later shown that proviral DNA is found in cells consistent with macrophages, microglia, astrocytes, oligodendrocytes, ependymal epithelium and choroid plexus (Sanna et al., 1999). Using rabbit antiserum to recombinant capsid and matrix proteins, some have had some success in identifying CAEV-infected cell types consistent with macrophage morphology in brain, spinal cord, lung, mammary gland, and lymph nodes (Storset et al., 1997). Identification of CAEV capsid-positive cells in the synovial fluid of CAEV-infected goats has been shown (Cheevers et al., 1994). Other specific cell-types that propagate CAEV infection in vitro include the following: synovial membrane cells, peripheral blood monocytes/macrophages, microglia, endothelial cells, mammary epithelial cells, granulosa cells and fibroblasts (Adams et al., 1980; Klevjer-Anderson and Cheevers, 1981; Klevjer-Anderson and Anderson, 1982; Anderson et al., 1983; Baszler et al., 1994; Adeyemo et al., 1996; Chebloune et al., 1996; Silva Teixeira et al., 1997; Lerondelle et al., 1999; Mselli-Lakhal et al., 2001; Lamara et al., 2001; Lechat et al., 2005).

Diagnosis

Clinical signs and the detection of antibodies to caprine arthritis-encephalitis virus (CAEV) in serum are the main techniques for CAEV diagnosis. Differential diagnosis exists for clinical signs caused by CAEV infection.

Clinical diagnosis

Clinical characterization of CAEV progressor status (chronic arthritis goats) and non-progressor status (asymptomatic goats) is subjective and depends primarily on the severity of arthritis. Adult CAEV progressor goats may exhibit debilitating lameness or severe arthritis and may show swelling of the carpel bursa, middle carpel and distal carpal joints or ‘water knee’. Other clinical signs associated with arthritis include lameness, reluctance to move and general recumbency. Radiographs can be very useful for identifying soft tissue mineralization osteoarthritis accompanied by osteolysis. There is a good correlation between radiographic abnormalities and the severity of the joint lesions (Woodard et al., 1982). A ratio of the circumference of the carpel and metacarpal (C/MC) regions is greater than 2.0 is a good clinical indicator of inflammatory radiocarpel lesions caused by CAEV infection and has been used to define progressor goats. However, in studies involving experimental infection C/MC ratios of greater than 2.0 typically occur 1-2 years after inoculation (Cheevers et al., 1988; Wilkerson et al., 1995b; Trujillo et al., 2004a).

Other clinical disease syndromes caused by CAEV infection in adult goats can occur singularly or in conjunction with CAEV-induced arthritis. These include mastitis or ‘hard-bag’ and chronic pneumonia characterized by dyspnoea. Kids experiencing encephalomyelitis typically display progressive hind-limb ataxia, paresis and paralysis; however, numerous non-specific clinical signs associated with white matter destruction and motor dysfunction are reported. Pneumonia presented as dyspnoea has been reported to occur with the neurological form of CAEV.

Lesions

If only postmortem investigation is available for diagnosis, gross and histological evaluation of target tissues (synovial lining of the carpal joints and bursa of the extensor carpal radialis tendon, central nervous system, mammary gland, lung, and lymph nodes) can be used to support the diagnosis of CAEV. Arthritis is characterized by mononuclear inflammation within the synovial lining and surrounding supportive tissue, proliferation of the synovium accompanied by oedema and necrosis in severe lesions. A semi-quantitative grading system for lesion severity in the radiocarpel joint has been developed for research studies (Cheevers et al., 2003). CNS lesions occur in the brain and spinal cord and include mild to moderate mononuclear meningoencephalitis including involvement of the choroid plexus, white matter gliosis, demyelination, oedema and hyperemia. Mammary gland lesions consist of minimal to severe infiltrates of mononuclear inflammatory cells in the periductal and periacinar stroma where severe lesions consist of coalescing infiltrates of inflammatory cells, lymphoid follicle formation, stroma oedema and fibrosis and inspissation or mineralization of duct contents (Cheevers et al., 1988). Lung lesions are generally mild to moderate and include interstitial infiltrates of mononuclear inflammatory cells predominately around airways and the pulmonary vasculature accompanied by variable hyperplasia of the respiratory epithelium. Typically in progressor goats there is marked hyperplasia of the lymphoid cells in the axillary and prescapular lymph nodes, which in severe cases can efface the normal nodal architecture.

Differential diagnosis

Differential diagnoses for CAEV-induced disease were reported by East (2002). Differential diagnoses for the neurological form of CAEV in goat kids include, but are not limited to, copper deficiency, lumbar cord abscesses, selenium and vitamin E deficiency, bacterial septicemia, septic arthritis or spinal cord injury. Differential diagnoses of the arthritic form of CAEV include septic arthritis, Chlamydia- and Mycoplasma-induced arthritis, and trauma. On occasion, the respiratory and cachexia forms of CAEV will manifest without clinical arthritis or encephalitis. The chronic form of pneumonia needs to be differentiated from lungworm infection, chronic bacterial pneumonia and pulmonary abscesses. The mastitis form of CAEV is often observed with the arthritic form of CAEV. The two primary differentials for mastitis in goats include bacterial infections and CAEV.

Laboratory diagnosis

Serological tests, PCR tests, immunohistochemical detection of CAEV antigens, and virus isolation are the four laboratory diagnostic tests used to confirm CAEV.

The presence of antibodies to CAEV in the serum of infected adult goats confirms infection and is the most reliable laboratory test. Serological diagnosis can be made using a variety of tests including Western blot analysis, immunoprecipitation (IP) of [³⁵S] methionine/cysteine-labeled CAEV, agar gel immunodiffusion assay, and ELISA. Western blot analysis and IP are typically used as confirmatory serological tests and are performed in a research laboratory setting. The CAEV AGID tests for the presence of antibody to the CAEV capsid protein, p28, and surface envelope glycoprotein, gp135; however, if the ovine progressive pneumonia virus (OPPV) AGID is used instead of the CAEV AGID with goat sera, approximately 40% of CAEV-positive goats will show negative (Knowles et al., 1994). ELISA tests are most commonly used for serological diagnosis, but some have better sensitivities and specificities than others do. Many ELISAs have been produced using whole CAEV and recombinant CAEV proteins (Simard et al., 2001; Clavijo and Thorsen, 1995; Rimstad et al., 1994; Celer et al., 1993; Heckert et al., 1992; Zanoni et al., 1991; Archambault et al., 1988). Indirect ELISAs are more problematic due to the dilutions required to lower background effects, which also increases the number of false negatives. The CAEV competitive inhibition ELISA (cELISA) does not require dilution of the sera before testing and since it depends on the presence of serological antibodies to bind to CAEV envelope glycoprotein (SU) and inhibit the binding of a monoclonal antibody to SU, the CAEV cELISA has a sensitivity of 100% and specificity of 96.4% when compared with IP (Herrmann et al., 2003). The CAEV cELISA offers a higher sensitivity than CAEV AGID when compared to IP (Knowles et al., 1994; Herrmann et al., 2003). However, the CAEV cELISA (96.4%) has a slightly lower specificity than CAEV AGID (100%), but this may be due to the increased sensitivity of the CAEV cELISA. Overall, results of CAEV serological tests are dependent on the infecting strain of CAEV; goats infected with a similar strain as the strain used in the serological test will test positive while goats infected with a markedly different strain of CAEV will test negative. If the animal has clinical signs of CAEV but tests negative in initial serological testing, different serological tests and other ancillary tests are advised. Moreover, a CAEV-seropositive kid goat, less than 1 year in age may be affected by passive transfer of material antibody, but may not necessarily be infected. Therefore, seropositive kid goats not displaying neurological disease or pneumonia should be tested by other means such as the PCR method described below.

PCR-based laboratory diagnostic tests for the detection of provirus in peripheral blood leukocytes (PBL) or peripheral blood mononuclear cells (PBMC) are becoming more common (Reddy et al., 1993; Rimstad et al., 1993; Barlough et al., 1994; Leroux et al., 1997; Wagter et al., 1998; Konishi et al., 2004). In addition, tissues and fluids such as brain, bone marrow, mammary gland, uterus, oviduct, seminal fluid, synovial membranes, lung, spinal cord, and lymph nodes have been found PCR-positive for CAEV in CAEV-infected goats (Barlough et al., 1994; Leroux et al., 1995; Travassos et al., 1998; Sanna et al., 1999; Fieni et al., 2003). At this time, PCR tests are considered secondary tests to serology. Some have found that PCR detection of CAEV provirus in peripheral blood mononuclear cells may precede seroconversion or antibody responses (Rimstad et al., 1993; Reddy et al., 1993); however, since false PCR positives are common, precautions are needed to reduce contamination and positives should be sequenced until the assay is optimized and validated (Zanoni et al., 1996). PCR diagnostic tests for CAEV have yet to be validated and, like serologic diagnostic tests, the sensitivity and specificity of PCR detection of CAEV depends upon sequence similarity of the infective provirus and the sequence used to develop primers. Therefore, primers for PCR amplification of CAEV provirus needs to be designed to amplify regions of the provirus with high similarity or regions conserved within all known small ruminant lentivirus (SRLV) provirus sequences. Although once optimized and validated, PCR tests for provirus in PBL or PBMC show promise in becoming an early indicator of CAEV-infection and may prove useful as a live-animal, confirmatory laboratory test.

Few studies have been published regarding immunohistochemical (IHC) detection of CAEV-infection in goats. CAEV-infected synovial cells in synovial fluid of CAEV-infected goats have been identified by immunohistochemical detection using monoclonal antibody 10A1, which binds to a capsid protein (p28) of CAEV (McGuire et al., 1987; Cheevers et al., 1994). Results of this study suggest that IHC could be used as a confirmatory test for CAEV-induced arthritis in live animals. Storset et al. (1997) identified CAEV-infected cells in brain, spinal cord, lung, mammary gland and lymph node tissues embedded in paraffin wax, followed by immunohistochemical detection using rabbit antiserum to recombinant capsid and matrix proteins. Results of this study suggest that IHC could be used as a postmortem test for CAEV-induced encephalitis, pneumonia, and mastitis. At present, there have been no dual immunohistochemical or immunofluorescence studies performed in situ identifying specific cell types in the joint, mammary gland, lung, lymph nodes, brain, or spinal cord that accumulate CAEV. This is presumably due to the low levels of replicating virus within macrophages, or the lack of adequate sampling in tissues.

Virus isolation is often performed in a research setting due to the high degree of technical difficulty and lack of sensitivity. Free viremia rarely or never occurs in CAEV-infected goats and isolation of virus from synovial fluid is sporadic. Therefore, suspected CAEV-infected cells or tissues are co-cultured with newborn goat synovial membrane cells for up to 6 weeks (Crawford et al., 1980). Synovial tissue from CAEV-infected goats can be cultured directly for up to 6 weeks. Mammary and peripheral blood mononuclear cells can be successfully co-cultured with goat synovial membrane cells (Cork and Narayan, 1980; Klevjer-Anderson et al., 1984; Kennedy-Stoskopf et al., 1985).

List of Symptoms/Signs

Disease Course

Adult goats naturally infected with caprine arthritis-encephalitis virus (CAEV) typically segregate into 2 groups: non-progressor (NP) (70%) and progressor goats (P) (30%) (Woodard et al., 1982). NP goats generally remain asymptomatic and develop humoral and cellular responses to CAEV antigens; however, NP goats can experience mild mastitis and loss of body condition. However, progressor goats become severely arthritic and may incur some lameness by sexual maturity (Woodard et al., 1982; Phelps and Smith, 1993). Typical signs of CAEV infection such as chronic arthritis, mastitis, cachexia, dyspnoea and chronic pneumonia are considered progressive, although intermittent disease can occur (Mdurvwa et al., 1994; Phelps and Smith, 1993; Ellis et al., 1988; Kennedy-Stoskopf et al., 1985). The course of disease is variable in progressors, with some animals showing mild to moderate lameness for years and others showing acute rapid progression leading to marked restriction of movement (Cheevers et al., 1988).

The neurological form of CAEV typically occurs in kids of 1-5 months of age where the primary clinical signs include depression, head tilt, torticollis and circling; however, CAEV infection in adult and juvenile goats can manifest as neurological disease (Norman and Smith, 1983; Phelps and Smith, 1993). Encephalomyelitis can be accompanied by chronic pneumonia manifested as dyspnoea and weight loss. The neurological form of CAEV is less frequently reported in CAEV-infected goats.

Epidemiology

Routes of transmission of CAEV are reviewed by Peterhans et al. (2004). Colostrum and milk are considered to be of prime importance in the transmission of CAEV from mother to offspring (Adams et al., 1983; East et al., 1993). Aerosol transmission between animals of all ages in close contact and over distances of up to several metres appears to be a significant route of spread both within and between flocks and herds, particularly under intensive housing or grazing conditions (East et al., 1993). The significance of intrauterine viral transmission is unclear. Semen has been shown to contain CAEV (Travassos et al., 1998) and Souza et al. (2013) demonstrated that the virus can be transmitted through artificial insemination with infected semen. Transmission by contaminated milking machines or buckets is considered to be a risk factor (Adams et al., 1983; Lerondelle et al., 1995). Humans may also contribute to the spread of infection by not changing clothing, boots and equipment when dealing with infected and unifected flocks (Greenwood et al., 1995). Live animal trading is considered a major risk factor in the spread of CAEV infection between herds (Contreras et al., 1998).

Impact: Economic

Disease caused by caprine arthritis-encephalitis virus (CAEV) is on the List of Diseases Notifiable to the World Organisation for Animal Health (OIE). These diseases are considered to be of socioeconomic and/or public health importance within countries and are significant in the international trade of animals and animal products. CAEV causes economic losses to the goat producer primarily due to the lack of goat exports in territories or countries that have high seroprevalence of CAEV. In addition, there have been significant associations made between positive CAEV serology and overall goat production and butterfat production in goatherds in the USA (Smith and Cutlip, 1988). A Spanish study of milk production losses associated with CAEV infection found that test-day milk yield was 10% less in seropositive compared to seronegative does (Martínez-Navalón et al., 2013).

Zoonoses and Food Safety

Caprine arthritis-encephalitis virus (CAEV) is not considered a zoonotic disease, and there are no regulations regarding human food safety and CAEV.

Disease Treatment

Currently, antiretroviral therapy is impractical in a field setting, and treatment is directed at the signs it causes rather than the virus itself. No cures are available for any known lentiviral infection.

Prevention and Control

Immunization and vaccines

There are no commercially available vaccines for caprine arthritis-encephalitis virus (CAEV) infection. In research settings, various vaccination strategies have been tested using niaive goats as an animal model for HIV vaccine development. These studies used inactivated CAEV, vaccinia-based CAEV genes with and without vaccinia-based cytokine genes, and plasmid-based CAEV genes with and without plasmid-based cytokine genes followed by challenge using CAEV molecular clones or CAEV field isolates (McGuire et al., 1986; Russo et al., 1993; Vitu et al., 1993; Cheevers et al., 1994; Cheevers et al., 2003). Most of these vaccination strategies have failed to protect against challenge. However, plasmid DNA vaccinations encoding CAEV SU followed by a boost with viral SU in Freund's incomplete adjuvant (SU-FIA) provided protection in 4 of 4 goats based upon the absence of severe radiocarpel joint lesions and lower provirus loads in the radiocarpel joint (Cheevers et al., 2003). More recently, a protein-based vaccination strategy using an engineered SU mutated at two sites E542N and R539S (SU-M) and administered subcutaneously with saponin adjuvant produced high titres of type-specific and cross-reactive neutralizing antibodies (Trujillo et al., 2004b). The production of long-lived cross-reactive neutralizing antibodies is a major goal of lentivirus vaccine strategies. Reina et al. (2013) review immunization strategies against small ruminant lentiviruses and progress that has been made towards the development of an effective vaccine.

Husbandry methods and good practice

Control and prevention methods for CAEV in goat herds have focused primarily on serological testing and isolating or culling infected goats, and heat inactivation of colostrum (56ºC for 1 h) and supplementation with bovine colostrum for kids born to CAEV-infected nannies (Adams et al., 1983; Rowe and East, 1997). Separating CAEV seropositive goats from seronegative goats has significantly helped the goat dairy industry by reducing the risk of transmission (Rowe et al., 1992b). These prevention and control strategies have not completely eradicated CAEV; however, utilizing a more sensitive serological diagnostic test such as cELISA to identify and eliminate seropositive goats annually can virtually eliminate the herd presence of CAEV over the course of 6 years in a commercial dairy goatherd (Herrmann et al., 2003). There are two reasons for incomplete eradication of CAEV. One is that there is delayed seroconversion where essentially seronegative goats are transmitting virus, and second, the serological test lacks sensitivity to detect all infected goats. Seropositive progressor goats transmit virus to niaive goats in a natural herd situation (Woodard et al., 1982); however, the transmission contribution of seropositive non-progressor goats remains to be determined. Furthermore, since lentiviruses and other infectious diseases can be transmitted through blood, re-use of needles should be discouraged.

Genetics

There is evidence that host genetics play a role in determining susceptibility/resistance to SRLV infection and disease progression, but little work has been performed in small ruminants (Herrmann-Hoesing et al., 2008; Larruskain and Jugo, 2013). A number of genes implicated in SRLV infection and disease have been identified, but more research is necessary to understand the host-SRLV interaction. A better understanding of loci involved in SRLV infection and pathology and their polymorphism could lead to the identification and selective breeding of naturally resistant animals (Heaton et al., 2012; White and Knowles, 2013).

References

Adams DS; Crawford TB; Klevjer-Anderson P, 1980. A pathogenetic study of the early connective tissue lesions of virus caprine arthritis-encephalitis. Am J. Pathol., 99(2):257-278.

Adams DS; Klevjer-Anderson P; Carlson JL; McGuire TC; Gorham JR, 1983. Transmission and control of caprine arthritis-encephalitis virus. American Journal of Veterinary Research, 44(9):1670-1675; 15 ref.

Adams DS; Oliver RE; Ameghino E; DeMartini JC; Verwoerd DW; Houwers DJ; Waghela S; Gorham JR; Hyllseth B; Dawson M; Trigo FJ; McGuire TC, 1984. Global survey of serological evidence of caprine arthritis-encephalitis virus infection. Veterinary Record, 115(19):493-495.

Adeyemo O; Phadtare L; Williams C, 1996. The response of goat brain cells to infection by caprine arthritis-encephalitis virus. Cellular and Molecular Biology, 42(8):1195-1209; 67 ref.

Anderson LW; Klevjer-Anderson P; Liggitt HD, 1983. Susceptibility of blood-derived monocytes and macrophages to caprine arthritis-encephalitis virus. Infect. Immun., 41(2):837-840.

Archambault D; East N; Perk K; Dahlberg JE, 1988. Development of an enzyme-linked immunosorbent assay for caprine arthritis-encephalitis virus. Journal of Clinical Microbiology, 26(5):971-975; 22 ref.

Banks KL; Adams DS; McGuire TC; Carlson J, 1983. Experimental infection of sheep by caprine arthritis-encephalitis virus and goats by progressive pneumonia virus. American Journal of Veterinary Research, 44(12):2307-2311; 35 ref.

Barlough J; East N; Rowe JD; Hoosear Kvan; DeRock E; Bigornia L; Rimstad E, 1994. Double-nested polymerase chain reaction for detection of caprine arthritis-encephalitis virus proviral DNA in blood, milk, and tissues of infected goats. Journal of Virological Methods, 50(1-3):101-114; 25 ref.

Baszler TV; Harwood WG; Lester KL; Davies WC; Knowles DP, 1994. Characterization of caprine microglial cells and in vitro infection with caprine arthritis-encephalitis lentivirus. Laboratory Investigation, 70(6):933-943; 52 ref.

Bertoni G; Zahno M-L; Zanoni R; Vogt H-R; Peterhans E; Ruff G; Cheevers WP; Sonigo P; Pancino G, 1994. Antibody Reactivity to the Immunodominant Epitopes of the Caprine Arthritis-Encephalitis Virus pg38 Transmembrane Protein Associates with the Development of Arthritis. J. Virol., 68(11):7139-7147.

Celer V; Zanoni RG; Peterhans E, 1993. [Comparison of various antigens in the diagnosis of caprine arthritis-encephalitis virus using the ELISA test]. Vet. Med. (Praha), 38(4):237-244.

Chebloune Y; Sheffer D; Karr BM; Stephens E; Narayan O, 1996. Restrictive type of replication of ovine/caprine lentiviruses in ovine fibroblast cell cultures. Virology (New York), 222(1):21-30; 40 ref.

Cheevers WP; Knowles DP; McGuire TC; Baszler TV; Hullinger GA, 1994. Caprine arthritis-encephalitis lentivirus (CAEV) challenge of goats immunized with recombinant vaccinia virus expressing CAEV surface and transmembrane envelope glycoproteins. Veterinary Immunology and Immunopathology, 42(3/4):237-251; 36 ref.

Cheevers WP; Knowles DP; McGuire TC; Cunningham DR; Adams DS; Gorham JR, 1988. Chronic disease in goats orally infected with two isolates of the caprine arthritis encephalitis lentivirus. Laboratory Investigation, 58(5):510-517; 53 ref.

Cheevers WP; McGuire TC, 1988. The lentiviruses: maedi/visna, caprine arthritis-encephalitis, and equine infectious anemia. Advances in Virus Research, 34:189-215; many ref.

Cheevers WP; Roberson S; Klevjer-Anderson P; Crawford TB, 1981. Characterization of Caprine Arthritis-Encephalitis Virus: A Retrovirus of Goats. Arch. Virol., 67:111-117.

Cheevers WP; Snekvik KR; Trujillo JD; Kumpula-McWhirter NM; Pretty On Top KJ; Knowles DP, 2003. Prime-boost vaccination with plasmid DNA encoding caprine-arthritis encephalitis lentivirus env and viral SU suppresses challenge virus and development of arthritis. Virology, 306:116-125.

Clavijo A; Thorsen J, 1995. Serologic Diagnosis of Caprine Arthritis-Encephalitis by ELISA with Two Recominant Proteins in a Parallel Testing Format. Journal of Immunoassay, 16(4):419-436.

Contreras A; Corrales JC; Sánchez A; Adúriz JJ; González L; Marco J, 1998. Caprine arthritis-encephalitis in an indigenous Spanish breed of dairy goat. Veterinary Record, 142(6):140-142; 21 ref.

Cork LC; Hadlow WJ; Crawford TB; Gorham JR; Piper RC, 1974. Infectious leukoencephalomyelitis of young goats. Journal of Infectious Diseases, 129(2):134-141.

Cork LC; Narayan O, 1980. The pathogenesis of viral leukoencephalomyelitis-arthritis of goats. I. Persistent viral infection with progressive pathologic changes. Lab. Invest., 42(6):596-602.

Crawford TB; Adams DS; Cheevers WP; Cork LC, 1980. Chronic Arthritis in Goats Caused by a Retrovirus. Science, 207:997-999.

Cruz JCMda; Singh DK; Lamara A; Chebloune Y, 2013. Small ruminant lentiviruses (SRLVs) break the species barrier to acquire new host range. Viruses, 5(7):1867-1884. http://www.mdpi.com/1999-4915/5/7/1867

Cutlip RC; Lehmkuhl HD; Sacks JM; Weaver AL, 1992. Prevalence of antibody to caprine arthritis-encephalitis virus in goats in the United States. J. Am. Vet. Med. Assoc., 200(6):802-805.

East NE, 2002. Caprine arthritis encephalitis. In: Smith BP, ed. Large Animal Internal Medicine. St Louis, USA: The CV Mosby Company, 1100-1101.

East NE; Rowe JD; Dahlberg JE; Theilen GH; Pedersen NC, 1993. Modes of transmission of caprine arthritis-encephalitis virus infection. Small Ruminant Research, 10(3):251-262.

Ellis TM; Robinson WF; Wilcox GE, 1988. The pathology and aetiology of lung lesions in goats infected with caprine arthritis-encephalitis virus. Australian Veterinary Journal, 65(3):69-73; 26 ref.

Fieni F; Rowe J; van Hoosear K; Burucoa C; Oppenheim S; Anderson G; Murray J; BonDurant R, 2003. Presence of caprine arthritis-encephalitis virus (CAEV) proviral DNA in genital tract tissues of superovulated dairy goat does. Theriogenology, 59:1515-1523.

Greenwood PL; North RN; Kirkland PD, 1995. Prevalance, spread and control of caprine arthritis-encephalitis virus in dairy goat herds in New South Wales. Australian Veterinary Journal, 72(9):341-345; 24 ref.

Heaton MP; Clawson ML; Chitko-Mckown CG; Leymaster KA; Smith TPL; Harhay GP; White SN; Herrmann-Hoesing LM; Mousel MR; Lewis GS; Kalbfleisch TS; Keen JE; Laegreid WW, 2012. Reduced lentivirus susceptibility in sheep with TMEM154 mutations. PLoS Genetics, 8(1):e1002467. http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002467

Heckert RA; McNab WB; Richardson SM; Briscoe MR, 1992. Evaluation of an enzyme-linked immunosorbent assay for the detection of antibodies to caprine arthritis-encephalitis virus in goat serum. Canadian Journal of Veterinary Research, 56(3):237-241; 25 ref.

Herrmann LM; Cheevers WP; McGuire TC; Adams DS; Hutton MM; Gavin WG; Knowles DP, 2003. Competitive-Inhibition Enzyme-Linked Immunosorbent Assay for Detection of Serum Antibodies to Caprine Arthritis-Encephalitis Virus: Diagnostic Tool for Successful Eradication. Clin. Diagn. Lab. Immunol., 10(2):267-271.

Herrmann-Hoesing LM; White SN; Mousel MR; Lewis GS; Knowles DP, 2008. Ovine progressive pneumonia provirus levels associate with breed and Ovar-DRB1. Immunogenetics, 60(12):749-758. http://springerlink.metapress.com/content/09640055641130u3/?p=b986d349e2cf4c119717428af4246f7f&pi=3

Houwers DJ; Konig CD; de Boer GF; Schaake J, 1983. Maedi-visna control in sheep. I. Artificial rearing of colostrum-deprived lambs. Vet. Microbiol., 8(2):179-185.

Johnson GC; Barbet AF; Klevjer-Anderson P; McGuire TC, 1983. Preferential Immune Response to Virion Surface Glycoproteins by Caprine Arthritis-Encephalitis Virus-Infected Goats. Infect. Immun., 41(2):657-665.

Johnson R; Pelzer KD, 1997. Food Animal Retroviruses. Veterinary Clinics of North America, Food Animal Practice, 13(1):i-xiv, 1-194; many ref.

Kennedy-Stoskopf S; Narayan O; Strandberg JD, 1985. The mammary gland as a target organ for infection with caprine arthritis-encephalitis virus. Journal of Comparative Pathology, 95(4):609-617; 14 ref.

Klevjer-Anderson P; Adams DS; Anderson LW; Banks KL; McGuire TC, 1984. A sequential study of virus expression in retrovirus-induced arthritis of goats. Journal of General Virology, 65(9):1519-1525; 23 ref.

Klevjer-Anderson P; Anderson LW, 1982. Caprine arthritis-encephalitis virus infection of caprine monocytes. J. Gen. Viol., 58(1):195-198.

Klevjer-Anderson P; Cheevers WP, 1981. Characterization of the infection of caprine synovial membrane cells by the retrovirus caprine arthritis-encephalitis virus. Virology, 110(1):113-119.

Knowles DJr; Cleevers W; McGuire T; Stem T; Gorham J, 1990. Severity of arthritis is predicted by antibody response to gp135 in chronic infection with caprine arthritis-encephalitis virus. Journal of Virology, 64(5):2396-2398; 15 ref.

Knowles DP; Evermann JF; Shropshire C; VanderSchalie J; Bradway D; Gezon HM; Cheevers WP, 1994. Evaluation of agar gel immunodiffusion serology using caprine and ovine lentiviral antigens for detection of antibody to caprine arthritis-encephalitis virus. Journal of Clinical Microbiology, 32(1):243-245; 17 ref.

Knowles DPJr, 1997. Laboratory diagnostic tests for retrovirus infections of small ruminants. Veterinary Clinics of North America, Food Animal Practice, 13(1):1-11; 64 ref.

Konishi M; Tsuduku S; Haritani M; Murakami K; Tsuboi T; Kobayashi C; Yoshikawa K; Kimura KM; Sentsui H, 2004. An Epidemic of Caprine Arthritis Encephalitis in Japan: Isolation of the Virus. J. Vet. Med. Sci., 66(8):911-917.

Lamara A; Fieni F; Mselli-Lakhal L; Tainturier D; Chebloune Y, 2001. Efficient replication of caprine arthritis-encephalitis virus in goat granulosa cells. Virus Research, 79(1/2):165-172; 38 ref.

Larruskain A; Jugo BM, 2013. Retroviral infections in sheep and goats: small ruminant lentiviruses and host interaction. Viruses, 5(8):2043-2061. http://www.mdpi.com/1999-4915/5/8/2043

Lechat E; Milhau N; Brun P; Bellaton C; Greenland T; Mornex JF; Le Jan C, 2005. Goat endothelial cells may be infected in vitro by transmigration of caprine arthritis-encephalitis virus-infected leucocytes. Vet. Immunol. Immunopathol., 104(3-4):257-263.

Lerondelle C; Godet M; Mornex JF, 1999. Infection of primary cultures of mammary epithelial cells by small ruminant lentiviruses. Veterinary Research, 30(5):467-474; 18 ref.

Lerondelle C; Greenland T; Jane M; Mornex JF, 1995. Infection of lactating goats by mammary instillation of cell-borne caprine arthritis-encephalitis virus. Journal of Dairy Science, 78(4):850-855.

Leroux C; Lerondelle C; Chastang J; Mornex JF, 1997. RT-PCR detection of lentiviruses in milk or mammary secretions of sheep or goats from infected flocks. Veterinary Research, 28(2):115-121; 18 ref.

Leroux C; Vuillermoz S; Mornex JF; Greenland T, 1995. Genomic heterogeneity in the pol region of ovine lentiviruses obtained from bronchoalveolar cells of infected sheep from France. Journal of General Virology, 76(6):1533-1537; 18 ref.

Martínez-Navalón B; Peris C; Gómez EA; Peris B; Roche ML; Caballero C; Goyena E; Berriatua E, 2013. Quantitative estimation of the impact of caprine arthritis encephalitis virus infection on milk production by dairy goats. Veterinary Journal, 197(2):311-317. http://www.sciencedirect.com/science/journal/10900233

McGuire TC; Adams DS; Johnson GC; Klevjer-Anderson P; Barbee DD; Gorham JR, 1986. Acute arthritis in caprine arthritis-encephalitis virus challenge exposure of vaccinated or persistently infected goats. American Journal of Veterinary Research, 47(3):537-540; 24 ref.

McGuire TC; Brassfield AL; Davis WC; Cheevers WP, 1987. Antigenic and structural variation of p28 core polypeptide of goat and sheep retroviruses. Journal of General Virology, 68(8):2259-2263; 21 ref.

McGuire TC; O’Rourke KI; Knowles DP; Cheevers WP, 1990. Caprine Arthritis Encephalitis Lentivirus Transmission and Disease. In: Oldstone MBA, Koprowski H, eds. Current Topics in Microbiology and Immunology, Retrovirus Infections of the Nervous System, Current and Future Perspectives. Berlin-Heidelberg, Germany: Springer-Verlag, 160: 61-76.

Mdurvwa EG; Ogunbiyi PO; Gakou HS; Reddy PG, 1994. Pathogenic mechanisms of caprine arthritis-encephalitis virus. Veterinary Research Communications, 18(6):483-490; 28 ref.

Mselli-Lakhal L; Guiguen F; Fornazero C; Favier C; Durand J; Grezel D; Moussa A; Mornex JF; Chebloune Y, 2001. Immortalized goat milk epithelial cell lines replicate CAEV at high level. Veterinary Research, 32(5):429-440; 33 ref.

Norman S; Smith MC, 1983. Caprine arthritis-encephalitis:Review of the neurologic form in 30 cases. JAVMA, 182(12):1342-1345.

O’Sullivan BM; Eaves FW; Baxendell SA; Rowan KJ, 1978. Leucoencephalomyelitis of goat kids. Aust. Vet. J., 54(10):479-483.

OIE Handistatus, 2002. World Animal Health Publication and Handistatus II (dataset for 2001). Paris, France: Office International des Epizooties.

OIE Handistatus, 2003. World Animal Health Publication and Handistatus II (dataset for 2002). Paris, France: Office International des Epizooties.

OIE Handistatus, 2004. World Animal Health Publication and Handistatus II (data set for 2003). Paris, France: Office International des Epizooties.

OIE Handistatus, 2005. World Animal Health Publication and Handistatus II (data set for 2004). Paris, France: Office International des Epizooties.

OIE, 2009. World Animal Health Information Database - Version: 1.4. World Animal Health Information Database. Paris, France: World Organisation for Animal Health. http://www.oie.int

Oliver R; Cathcart A; McNiven R; Poole W; Robati G, 1985. Infection of lambs with caprine arthritis encephalitis virus by feeding milk from infected goats. Veterinary Record, 116(3):83; 4 ref.

Peretz G; Asso J; Devillechaise P, 1993. Caprine arthritis encephalitis virus: review of present knowledge and practical measures. Revue de Médecine Vétérinaire, 144(2):93-98; 10 ref.

Perrin GG; Polack B, 1992. Caprine arthritis encephalitis: a review. V International Conference on Goats: March 1992. Pre-conference proceedings: invited papers Volume 2, Part 2., 568-574; 39 ref.

Peterhans E; Greenland T; Badiola J; Harkiss G; Bertoni G; Amorena B; Eliaszewicz M; Juste RA; Krassnig R; Lafont JP; Lenihan P; Pétursson G; Pritchard G; Thorley J; Vitu C; Mornex JF; Pépin M, 2004. Routes of transmission and consequences of small ruminant lentiviruses (SRLVs) infection and eradication schemes. Veterinary Research, 35(3):257-274.

Phelps SL; Smith MC, 1993. Caprine arthritis-encephalitis virus infection. Journal of the American Veterinary Medical Association, 203(12):1663-1666; 22 ref.

Pisoni G; Bertoni G; Puricelli M; Maccalli M; Moroni P, 2007. Demonstration of coinfection with and recombination by caprine arthritis-encephalitis virus and maedi-visna virus in naturally infected goats. Journal of Virology, 81(10):4948-4955. http://jvi.asm.org/

Reddy PG; Sapp WJ; Heneine W, 1993. Detection of caprine arthritis-encephalitis virus by polymerase chain reaction. Journal of Clinical Microbiology, 31(11):3042-3043; 13 ref.

Reina R; Andrés Dde; Amorena B, 2013. Immunization against Small Ruminant Lentiviruses. Viruses, 5(8):1948-1963. http://www.mdpi.com/1999-4915/5/8/1948

Rimstad E; East N; DeRock E; Higgins J; Pedersen NC, 1994. Detection of antibodies to caprine arthritis-encephalitis virus using recombinant gag proteins. Archives of Virology, 134(3/4):345-356; 30 ref.

Rimstad E; East NE; Torten M; Higgins J; DeRock E; Pedersen NC, 1993. Delayed seroconversion following naturally acquired caprine arthritis-encephalitis virus infection in goats. American Journal of Veterinary Research, 54(11):1858-1862; 33 ref.

Rolland M; Mooney J; Valas S; Perrin G; Mamoun RZ, 2002. Characterisation of an Irish caprine lentivirus strain - SRLV phylogeny revisited. Virus Research, 85(1):29-39; 19 ref.

Rowe JD; East NE, 1997. Risk factors for transmission and methods for control of caprine arthritis-encephalitis virus infection. Veterinary Clinics of North America, Food Animal Practice, 13(1):35-53; 69 ref.

Rowe JD; East NE; Franti CE; Thurmond MC; Pedersen NC; Theilen GH, 1992. Risk factors associated with the incidence of seroconversion to caprine arthritis-encephalitis virus in goats on California dairies. American Journal of Veterinary Research, 53(12):2396-2403; 24 ref.

Rowe JD; East NE; Thurmond MC; Franti CE; Pedersen NC, 1992. Cohort study of natural transmission and two methods for control of caprine arthritis-encephalitis virus infection in goats on a California dairy. American Journal of Veterinary Research, 53(12):2386-2395; 35 ref.

Russo P; Vitu C; Fontaine JJ; Vignoni M, 1993. Caprine arthritis-encephalitis: trials of a vaccine with adjuvant. I. Clinical and virological study. Comparative Immunology, Microbiology and Infectious Diseases, 16(2):131-136; 10 ref.

Sanna E; Sanna MP; Vitali CG; Renzoni G; Sanna L; Spano S; Rossi G; Leoni A, 1999. Proviral DNA in the brains of goats infected with caprine arthritis-encephalitis virus. Journal of Comparative Pathology, 121(3):271-276; 8 ref.

Shah C; Huder JB; Böni J; Schönman M; Mühlherr J; Lutz H; Schüpbach J, 2004. Direct Evidence for Natural Transmission of Small-Ruminant Lentiviruses of Subtype A4 from Goats to Sheep and Vice Verca. J. Virol., 78(14):7518-7522.

Sigurdsson B; Palsson PA; Tryggvaddottir A, 1953. Transmission experiments with maedi. J. Infect. Dis., 93(2):166-175.

Silva Teixeira MFda, 1997. Immortalization of caprine fibroblasts permissive for replication of small ruminant lentiviruses. American Journal of Veterinary Research, 58(6):579-584; 30 ref.

Simard C; Kibenge MT; Singh P; Dixon P, 2001. Simple and rapid method for production of whole-virus antigen for serodiagnosis of caprine arthritis-encephalitis virus by enzyme-linked immunosorbent assay. Clinical and Diagnostic Laboratory Immunology, 8(2):352-356; 25 ref.

Smith MC; Cutlip R, 1988. Effects of infection with caprine arthritis-encephalitis virus on milk production in goats. Journal of the American Veterinary Medical Association, 193(1):63-67; 17 ref.

Souza KCde; Pinheiro RR; Santos DO; Brito RLLde; Rodrigues Ade S; Sider LH; Paula NRO; Avila AA; Cardoso Jde FS; Andrioli A, 2013. Transmission of the caprine arthritis-encephalitis virus through artificial insemination. Small Ruminant Research, 109(2/3):193-198. http://www.sciencedirect.com/science/journal/09214488

Storset AK; Evensen O; Rimstad E, 1997. Immunohistochemical identification of caprine arthritis-encephalitis virus in paraffin-embedded specimens from naturally infected goats. Veterinary Pathology, 34(3):180-188; 39 ref.

Sundquist B, 1981. Goat visna virus: isolation of a retrovirus related to visna virus of sheep. Arch. Virol., 68(2):115-127.

Travassos C; Benoît C; Valas S; Silva Ada; Perrin G, 1998. Detection of caprine arthritis encephalitis virus in white blood mononuclear cells and semen of experimentally infected bucks. Veterinary Research, 29(6):579-584; 22 ref.

Trujillo JD; Hötzel KJ; Snekvik KR; Cheevers WP, 2004. Antibody response to the surface envelope of caprine arthritis-encephalitis lentivirus: disease status is predicted by SU antibody isotype. Virology, 325:129-136.

Trujillo JD; Kumpula-McWhirter NM; Hötzel KJ; Gonzalez M; Cheevers WP, 2004. Glycosylation of Immunodominant Linear Epitopes in the Carboxy-Terminal Region of the Caprine Arthritis-Encephalitis Virus Surface Envelope Enhances Vaccine-Induced Type-Specific and Cross-Reactive Neutralizing Antibody Responses. J. Virol., 78(17):9190-9202.

Vitu C; Russo P; Vignoni RM, 1993. Caprine arthritis-encephalitis: trials of a vaccine with adjuvant-II. A study of the antibody response. Comparative Immunology, Microbiology and Infectious Diseases, 16(2):137-144; 11 ref.

Von Bodungen U; lechner F; Pfister H; Vogt HR; Cheevers WP; Bertoni G; Jungi TW; Peterhans E, 1998. Immunohistology of the early course of lentivirus-induced arthritis. Clin. Exp. Immunol., 111(2):384-390.

Wagter LHA; Jansen A; Bleumink-Pluym NMC; Lenstra JA; Houwers DJ, 1998. PCR detection of lentiviral GAG segment DNA in the white blood cells of sheep and goats. Veterinary Research Communications, 22(5):355-362; 12 ref.

White SN; Knowles DP, 2013. Expanding possibilities for intervention against small ruminant lentiviruses through genetic marker-assisted selective breeding. Viruses, 5(6):1466-1499. http://www.mdpi.com/1999-4915/5/6/1466

Wilkerson MJ; Davis WC; Baszler TV; Cheevers WP, 1995. Immunopathology of Chronic Lentivirus-Induced Arthritis. Am. J. Pathol., 146(6):1433-1443.

Wilkerson MJ; Davis WC; Cheevers WP, 1995. Peripheral Blood and Synovial Fluid Mononuclear Cell Phenotypes in Lentivirus Induced Arthritis. J. Rheumatol., 22(1):8-15.

Woodard JC; Gaskin JM; Poulos PW; MacKay RJ; Burridge MJ, 1982. Caprine arthritis-encephalitis:clinicopathologic study. Am. J. Vet. Res., 43(12):2085-2096.

Zanoni RG, 1998. Phylogenetic analysis of small ruminant lentiviruses. Journal of General Virology, 79(8):1951-1961; 4 ref.

Zanoni RG; Cordano P; Nauta IM; Peterhans E, 1996. PCR for the detection of lentiviruses from small ruminants. Schweiz. Arch. Tierheilkd., 138(2):93-98.

Zanoni RG; Nauta IM; Kuhnert P; Pauli U; Pohl B; Peterhans E, 1992. Genomic heterogeneity of small ruminant lentiviruses detected by PCR. Veterinary Microbiology, 33(1-4):341-351; [Proceedings of the Second Congress of the European Society for Veterinary Virology, Uppsala, Sweden, Sept 24-26th 1991]; 36 ref.

Zanoni RG; Nauta IM; Pauli U; Peterhans E, 1991. Expression in Escherichia coli and sequencing of the coding region for the capsid protein of Dutch maedi-visna virus strain ZZV 1050: application of recombinant protein in enzyme-linked immunosorbent assay for the detection of caprine and ovine lentiviruses. Journal of Clinical Microbiology, 29(7):1290-1294; 47 ref.

Zink MC; Yager JA; Myers JD, 1990. Pathogenesis of caprine arthritis encephalitis virus. Cellular localization of viral transcripts in tissues of infected goats. American Journal of Pathology, 136(4):843-854; 30 ref.

Özyörük F; Cheevers WP; Hullinger GA; McGuire TC; Hutton M; Knowles DP, 2001. Monoclonal antibodies to conformational epitopes of the surface glycoprotein of caprine arthritis-encephalitis virus: potential application to competitive-inhibition enzyme-linked immunosorbent assay for detecting antibodies in goat sera. Clinical and Diagnostic Laboratory Immunology, 8(1):44-51; 53 ref.

Distribution Maps