visna/maedi virus

Other Scientific Names

• maedi virus
• maedi-visna virus (Pepin et al., 1998)
• visna virus
• visna/maedi virus (strain 1514)
• visna-maedi virus

International Common Names

• English: ovine lentivirus; ovine progressive pneumonia virus

English acronym

• MVV
• VISNA
• VMV

• Domain: Virus
•     Group: "DNA and RNA reverse transcribing viruses"
•         Family: Retroviridae
•             Genus: Lentivirus
•                 Species: visna/maedi virus

Visna/maedi virus is the prototype Lentivirus belonging to subfamily Lentivirinae of the family Retroviridae, together with human immunodeficiency viruses (HIV-1 and HIV-2 viruses), caprine arthritis-encephalitis virus (CAEV), and the simian, bovine, feline immunodeficiency viruses (SIV, BIV and FIV respectively), and equine infectious anaemia virus (EIAV). Importantly, visna/maedi virus is a species-specific but not oncogenic virus. Depending on the cell type, visna/maedi virus infection may lead to a cytopathic effect, or remain unnoticed. This has important consequences for pathology and viral persistence.

Visna/maedi virus is a dimer of positive sense RNA of about 9.2 kb in size (Carey and Dalziel, 1993). Virus replication occurs by reverse transcription of the genome using the virus-encoded RNA-dependent DNA polymerase, and occurs via a DNA intermediate. Part of the proviral DNA is incorporated into the host genome. The genome of lentiviruses contains the structural genes (gag-group specific antigen and env-envelope), and enzymatic gene (pol-polymerase), typical for retroviruses. Analogous to other retroviruses, visna/maedi virus proviral DNA is flanked by long terminal repeats (LTR) that provide the cis signals required for transcription, integration and polyadenylation of viral RNA. LTR of visna/maedi virus may be involved in cell tropism (Agnarsdottir et al., 2000).

The gag-gene encodes for three proteins: the capsid or core protein (p25), the nucleocapsid (p14) and the matrix (MA) protein (p17), which ensures the link between the capsid and the envelope. The hydrophobic capsid protein is the most abundant constituent protein of visna\maedi virus. This capsid protein elicits a strong induction of antibodies upon infection, an effect that is used in diagnostic tests.

The env-gene encodes the glycoprotein of the virus. The precursor protein gp160 is cleaved into two subunits: the surface glycoprotein (SU: gp135), and the transmembrane glycoprotein (TM: gp44). The envelope glycoproteins of visna\maedi virus have important biological functions. They contain epitopes responsible for the induction of neutralising antibodies, and for interaction with cellular receptors during the replication cycle.

The pol-gene encodes the RNA-dependent DNA-polymerase, which is a heterodimer that permits transcription of the viral RNA into DNA.

Other visna/maedi virus-encoded enzymes are dUTPase, integrase and protease (Pepin et al., 1998).

Auxiliary genes that are not essential for virus replication further mediate the level of viral expression in lentiviruses. Visna/maedi virus also contains several short, multiply spliced ORFs that encode proteins which are thought to have regulatory function (Carey and Dalziel, 1993). Visna/maedi virus has three auxiliary genes: tat, vif-viral infectivity factor (previously called Q gene) and rev-regulator of virion protein expression.

The tat-gene encodes a 10 kDa protein, and mediates the accumulation of viral RNA. The vif-gene encodes a 29 kDa protein, and induces a weak immune response and is thought to play a role in the late stages of the viral life cycle, specifically during the morphogenesis of the viral nucleoprotein core. The rev-gene encodes a 19 kDa protein and plays a role in the early phase of visna\maedi virus replication, by transporting unspliced mRNA from the nucleus to the cytoplasm. The rev gene seems to be essential for visna/maedi virus replication as the rev-mutagenised virus appears uninfectious (Pepin et al., 1998).

Lentiviruses can be roughly separated into two groups based on their cell tropism. Visna/maedi virus, CAEV and EIAV replicate strictly in macrophages and monocytes, whereas the primate lentiviruses HIV and SIV also replicate in CD4+ lymphocytes (Narayan et al., 1997). Importantly, lentiviruses are capable to replicate in non-dividing terminally differentiated cells. This implies that cellular DNA replication is not required for integration of the viral DNA into the cellular genome. It is currently unknown whether the auxiliary genes of the lentiviruses, as opposed to the oncogenic retroviruses, play a role in altering the non-dividing cells to provide the necessary enzymes and metabolites for viral DNA replication and integration (Clements et al., 1994; Narayan et al., 1997).

The Lentivirusgag, pol en env genes encode proteins that comprise the infectious viral particle. Lentiviruses bud from the cell membrane in a fashion similar to the oncogenic retroviruses. However, in some cell types such as macrophages and endothelial cells, lentiviruses bud internally into intracellular vacuoles, thereby providing a reservoir of infectious virus particles that are not exposed to the cell surface and cannot be recognised by the immune system (Narayan et al., 1997).

After infection, the virus can establish itself into the genomic material of the host as proviral DNA, and reside in a quiescent proviral state for several months. At a given moment the virus is activated by cellular and viral factors and the disease starts to develop.

Genetically, lentiviruses are quite heterogeneous. This may contribute to persistence in the host by permitting immune evasion. The antigenic diversity also presents a huge obstacle in Lentivirus vaccine development. Antigenically distinct viruses have been isolated from sheep persistently infected with visna/maedi virus. These variants arose from mutations in the env-gene (Pepin et al., 1998).

Various strains of visna/maedi virus differ in their pathogenicity in vitro and in vivo. This may be accompanied by differences in phenotypic characteristics such as absence of cytopathic effect in alveolar macrophages.

Disease(s) associated with this pathogen is/are on the list of diseases notifiable to the World Organisation for Animal Health (OIE). The distribution section contains data from OIE's Handistatus database on disease occurrence. Please see the AHPC library for further information 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.