Visna-maedi virus

Visna virus
Virus classification
(unranked):	Virus
Realm:	Riboviria
Kingdom:	Pararnavirae
Phylum:	Artverviricota
Class:	Revtraviricetes
Order:	Ortervirales
Family:	Retroviridae
Genus:	Lentivirus
Species:	Visna virus
Synonyms
Maedi virus

Visna-maedi virus (also known as Visna virus, Maedi-visna virus and Ovine lentivirus

Visna infection may progress to total paralysis leading to death via inanition; however, if given assistance in eating and drinking, infected animals may survive for long periods of time, sometimes greater than ten years.^[9] Viral replication is almost exclusively associated with macrophages in infected tissues; however, replication is restricted in these cells—that is, the majority of cells containing viral RNA do not produce infectious virus.^[5]

The disease was introduced to Iceland following an import of Karakul sheep from Germany in 1933.^[6] The susceptibility to maedi-visna infection varies across sheep breeds, with coarse-wool breeds apparently more susceptible than fine-wool sheep.^[6] Attempts at vaccination against maedi-visna virus have failed to induce immunity, occasionally causing increased viremia and more severe disease.^[7] Eradication programs have been established in countries worldwide.^[6]

Associated diseases and Clinical Signs

Visna – Maedi is a chronic viral disease prevalent in adult sheep. The disease is rarely found in certain species of goat. Maedi Visna virus is also referred to as ovine progressive pneumonia (OPP). This disease corresponds to two clinical entities caused by the same virus. Maedi is a form that results in a chronic progressive pneumonia. Visna refers to the neurological form of the disease and predominantly causes meningoencephalitis in adult sheep. This disease has inflicted many economic losses worldwide due to the long incubation period and the high mortality rate of sheep and goats. MV virus can infect sheep of any age but clinical symptoms rarely occur in sheep less than two years old. The onset of the diseases is gradual resulting in relentless loss of weight in addition to breathing problems. Cough, abortion, rapid breathing, depression, chronic mastitis and arthritis are also additional symptoms observed. These symptoms appear mostly in animals over the age of three and therefore might spread to other flocks before clinical diagnosis can be achieved. Animals showing the above symptoms might die within six months of infection. This causal lentivirus can be found in monocytes, lymphocytes and macrophages of infected sheep in the presence of humoral and cell mediated immune response and can also be detected by conducting several serological tests.^[10] Transmission of the disease occurs most commonly via the oral route caused by ingestion of colostrum or milk that contains the virus or inhalation of infected aerosol droplets. Due to variation of the strains of MVV, some of the association clinical symptoms may be more pre-dominant in a flock relative to others along with differences in genetic susceptibility patterns.^[11]

Viral replication

Entry

Visna Maedi virus (VMV) belongs to the small ruminant

Horizontal transmission plays an important role among livestock due to their often close quarters, especially during winter stabling. Free virus or virus infected cells are generally transferred in through inhalation of respiratory secretions. Additionally, fecal-oral transmission often occurs through contamination of drinking water.^[20] Sexual transmission has also been shown to be possible.^[21] No link has yet been made between transmission and other excretory products such as saliva and urine.^[20]

Vertical transmission

In endemically infected flocks of livestock, free virus and virus infected cells are passed through from mothers to lambs via colostrum and milk.^[22] This is one of the key features in affected populations, as it contributes greatly to the virus becoming endemic in the flock.^[23] Lambs are extremely vulnerable to infection due to the permeability of the guts of newborns.^[24]

Virion structure

Visna virus particles are spheres approximately 100 nm in diameter. Virions consist of an

Infection can also occur in mammary epithelial and endothelial cells, implying mammary glands as a main viral reservoir, showing the importance that vertical transmission plays in the spread of the virus.[26]

Genome structure

Visna virus has a positive-strand RNA genome approximately 9.2 kilobases in length. As a

The viral tat gene encodes a 94-amino acid protein. Tat is the most enigmatic of the proteins of the visna virus. Most studies have indicated that Tat is a transcription factor necessary for viral transcription from the LTRs. Tat contains both a suppressor domain and a powerful acidic activator domain on the N-terminus.^[32] It has been suggested that Tat interacts with the cellular AP-1 transcription factors Fos and Jun to bind to the TATA-binding protein and activate transcription.^[29] However, other studies have suggested that the visna virus "Tat" protein is not a trans-activator for transcription but instead exhibits a function involved in cell cycle arrest, making it more closely related to the HIV-1 Vpr protein than Tat.^[33]

The viral rev gene encodes a post-transcriptional regulatory protein.^[34] Rev is required for expression of unspliced or partially spliced mRNA coding for the viral envelope protein, including gag and env in a similar manner as the HIV Rev protein.^[35] Rev binds as a multimer to the Rev Response Element (RRE) which has a stem-loop secondary structure.

The function of the auxiliary gene vif is not fully known. The vif gene product, a 29 kDa protein, induces a weak immune response in animals.^[36] Deletion experiments have demonstrated that the vif gene is essential for infectivity.^[37]

Model system for HIV infection

Though it does not produce severe