Anemia 2013 July-2

 

The origin of lentivirus research: Maedi-visna virus.

Curr HIV Res. 2013 Jan;11(1):2-9.

Thormar H.

University of Iceland, Reykjavik, Iceland. halldort@hi.is

Abstract

Maedi and visna are contagious sheep diseases which were introduced into Iceland in 1933 by imported sheep of Karakul breed. Maedi, a slowly progressing pneumonia, and the central nervous system disease visna were shown to be transmissible in sheep and most likely caused by a virus. In 1957, visna virus was isolated in tissue culture from sheep brain and maedi virus was isolated the following year from sheep lungs. Both viruses showed similar cytopathic effect in tissue culture. Electron microscope studies of ultrathin sections from visna virus infected cells demonstrated spherical particles, 70-100 nm in diameter, which were formed by budding from the cell membrane. Later studies showed identical particles in maedi virus infected cultures. These, and several other comparative studies, strongly indicated that maedi and visna were caused by strains of the same virus, later named maedi-visna virus (MVV). Comparative studies in tissue culture suggested that MVV was related to RNA tumor viruses of animals, the oncornaviruses. This was later supported by the finding that MVV is an RNA virus. A few months after reverse transcriptase was demonstrated in oncornaviruses, the enzyme was also found in MVV virions. Thus, MVV was classified as a retrovirus together with the oncornaviruses. However, MVV is not oncogenic in vivo or in vitro and was in 1975 placed in a subgroup of retroviruses named lentiviruses, which cause cytopathic effect in vitro and slowly progressing inflammatory disease in animals, but are nononcogenic. In the early 1980s, the causative agent of AIDS was found to be a non-oncogenic retrovirus and was classified as a lentivirus. Thus, HIV became the first human lentivirus.

PMID: 23278353

 

Supplementary information

In the early 1980s, a virus was isolated from patients with AIDS. Electron microscopy of lymphocytes infected with the viral isolates showed particles budding from the cell membrane similar to RNA tumor viruses. Detection of reverse transcriptase in the supernatant of infected lymphocytes showed that this was a retrovirus. Further studies comfirmed that the newly discovered virus was a member of the lentivirus group of non-oncogenic retroviruses. In 1986, the virus, identified as the causative agent of AIDS, was named human immunodeficiency virus, HIV.

In the late 1950s, a virus was isolated from Icelandic sheep with a rare disease, maedi-visna, which affected the lungs and occasionally the central nervous system (CNS). Electron microscope studies indicated that this virus was related to RNA tumor viruses and later studies confirmed that it was a non-oncogenic retrovirus which was named maedi-visna virus (MVV). Related animal viruses, such as caprine arthritis-encephalitis virus (CAEV) of goats and equine infectious anemia virus (EIAV) of horses were grouped together with MVV in a new non-oncogenic genus of the Retroviridae family, the lentiviruses, of which MVV was the prototype.

The name lentivirus refers to SigurdssonĀ“s concept of slow infections, lenti meaning slow. Slow infections, as defined by Sigurdsson in 1954, are characterized by 1) a long incubation period without clinical signs lasting for many months to several years and 2) a slowly progressing clinical course always leading to death. MVV was the first lentivirus, isolated from sheep with a slow infection of the lungs and CNS. The first human lentivirus, HIV, was isolated about 30 years later from patients with AIDS, an infection of the immune system showing the hallmarks of a slow infection. The events leading to the discovery and characterization of the animal and human lentiviruses, as described in this paper, are remarkably similar.

 

The importance of placing the newly isolated human retrovirus in the group of animal lentiviruses was pointed out by Montagnier [3], who suggested that relevant information about the pathogenic mechanisms in AIDS might be drawn from comparison with animal models. Maedi-visna virus and the pathogenesis of the slow infection it causes in sheep had already been studied for decades before the emergence of the AIDS epidemic. The prediction of Montagnier in 1985 has proved to be surprisingly correct, because AIDS in humans shows the hallmarks of a slow virus infection as exemplified by maedi-visna [5,6]. As formulated by Sigurdsson in 1954 [5], these are 1) a long incubation period lasting for many months to several years and 2) a slowly progressing clinical course always leading to death. The early course of the animal and human infections is strikingly similar. The most important difference appears in the late stages of AIDS and is due to the T-lymphocyte tropism of HIV which leads to depletion of CD4+ T-lymphocytes and to immunodeficiency. This does not happen in maedi-visna because of the lack of T-cell tropism in the virus. The difference in cell tropism is therefore responsible for the different pathological processes which take place in late stages of these virus infections, and for the difference in the final clinical manifestation.

Lentivirus refers to SigurdssonĀ“s concept of slow infections, lenti meaning slow.

Maedi-visna virus was the first lentivirus isolated and characterized in detail as the prototype for lentiviruses of animals. The closely related caprine arthritis-encephalitis virus (CAEV) of goats was isolated and characterized in 1980 [56]. In 1976, reverse transcriptase was detected in equine infectious anemia virus (EIAV) of horses [57] and further characterized in 1977 [58]. Together, these viruses belong to the non-oncogenic Lentivirinae genus of the Retroviridae family. Although the Icelandic name maedi-visna virus has generally been accepted worldwide, ovine progressive pneumonia (OPP) virus is commonly used in the United States. The name ovine lentivirus (OvLV) is also used. After experimental infection of sheep by CAEV and goats by MVV [59] they were grouped together as small ruminant lentivirus (SRLV)

Conclusion

After the isolation of HIV in the 1980s, electron microscope studies showed virus particles budding from the membrane of infected cells, similar to RNA tumor virus particles. When the virus was found to contain reverse transcriptase it was classified as a retrovirus. Further studies showed that HIV, and the related simian immunodeficiency viruses, were not oncogenic and therefore fit into the genus of Lentivirinae. Before this time, lentiviruses were mostly of interest to veterinarians and a small group of dedicated virologists who believed that they were in many respects a unique type of viruses. After the discovery of HIV, lentivirus became a household word and lentiviruses the most studied and best known of all viruses. Previously, diseases caused by lentiviruses had mostly been of concern to sheep farmers who suffered economic losses due their insidious, slowly progressing course and fatal outcome. Now, a similar disease caused by a human lentivirus suddenly became a threat to mankind. However, the chain of events leading to the discovery and characterization of the animal and human lentiviruses, as described in this report, is remarkably similar.

 

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