Simian immunodeficiency virus

The simian (monkey-hosted) immunodeficiency viruses are a species of retrovirus in the Primate group of genus Lentivirus along with the human viruses HIV-1 and HIV-2 that cause AIDS, and a few other viruses that infect other primates. Related viruses in other groups in the genus infect other mammals like sheep and goats, horses, cattle, cats and a few others. The genus is one of 6 genera in subfamily orthoretrovirinae which together with genus Spumavirus form family retroviridae of all RNA retroviruses (RNA viruses which use a DNA intermediate).[8]

The ICTVdB code of SIV is 61.0.6.5.003.[9] Although HIV-1 and HIV-2 cladistically fall into SIV,[10] ICTV considers them distinct species from ordinary, non-human-infecting SIV.

Immunodeficiency resembling human AIDS was reported in captive monkeys in the United States beginning in 1983.[16][17][18] SIV was isolated in 1985 from some of these animals, captive rhesus macaques suffering from simian AIDS (SAIDS).[17] The discovery of SIV was made shortly after HIV-1 had been isolated as the cause of AIDS and led to the discovery of HIV-2 strains in West Africa. HIV-2 was more similar to the then-known SIV strains than to HIV-1, suggesting for the first time the simian origin of HIV. Further studies indicated that HIV-2 is derived from the SIVsmm strain found in sooty mangabeys, whereas HIV-1, the predominant virus found in humans, is derived from SIV strains infecting chimpanzees (SIVcpz).

Chimpanzees are not believed to be the original hosts of an independent lineage of SIV, but rather that SIVcpz is a relatively recent acquisition resulting from a recombination of SIVgsn (greater spot-nosed monkeys) and SIVrcm (red-capped mangabeys) within the host chimpanzee. It is known that chimpanzees hunt and consume these monkeys for food.[19] In 2010, researchers reported that SIV had infected monkeys in Bioko for at least 32,000 years. Based on molecular clock analyses of sequences, it was previously thought by many that SIV infection in monkeys had happened over the past few hundred years.[20] Scientists estimated that it would take a similar amount of time before humans would adapt naturally to HIV infection in the way monkeys in Africa have adapted to SIV and not suffer any harm from the infection.[21]

In 2008, discovery of an endogenous lentivirus in a prosimian (proto-monkey) primate, the gray mouse lemur native to Madagascar, pushed the origin of SIV-like lentivirus infections in primates back to at least 14 Ma, the last time there was intermingling of mammals between the island of Madagascar and the African mainland, if the infection is attributed to horizontal transmission between homologous hosts. If the virus and host were coevolved, rather than acquired, that potentially pushes the date of the endogenous event back to approx. 85 Ma, the split between the lemur-like and monkey-like primate lineages. That date barely antedates the emergence of the primates 87.7 Ma.[22]

About 100,000 cells from rhesus macaques, grouped by similarity. Red cells are from monkeys infected with simian-human immunodeficiency virus, while blue cells are from uninfected ones.

SIV pathogenesis encompasses both pathogenic and non-pathogenic SIV infections. SIV infection of non-human primates (NHPs) invariably results in persistent infection, but rarely acute disease. Pathogenic infection is typified by Rhesus macaques infected with SIV strains derived from sooty mangabeys. Disease progression to AIDS occurs within a period of months to years, depending upon the SIV strain used. Non-pathogenic infection is typified by African NHPs naturally infected with SIV. These animals rarely progress to AIDS despite maintaining viral loads that are equivalent to SIV viral loads in pathogenic infections. It is postulated that AIDS-like disease in African NHPs represents horizontal transmission of the virus from one or more homologous species in the recent evolutionary past, before equilibrium of co-adaptation has occurred.

The similarities of the two types of virus infections:[24]

• high level of virus replication during primary infection (0–180 days)
• high level of CD4+ T-cell loss (0–180 days)
• restricted role of humoral immune response

The differences (what happens in primates):

• lower level of CCR5+ T-cells
• stable level of viral replication (180 days-years)
• restoration of CD4+ T-cells
• early cytokine production (0–10 days after infection)
• normal level of immune activation
• high level of functional immune cells
• establishment of anti-inflammatory milieu

Beatrice Hahn of the University of Pennsylvania and a team of researchers in 2009 found that chimpanzees do die from simian AIDS in the wild and that the AIDS outbreak in Africa has contributed to the decline of chimpanzee populations. Testing wild chimpanzees, researchers detected organ and tissue damage similar to late-stage human AIDS. The infected chimpanzees had a 10 to 16 times greater risk of dying than uninfected ones; infected females were less likely to give birth, could pass the virus to their infants, and had a higher infant mortality rate than uninfected females.[25][26] Bonobos appear to avoid simian immunodeficiency virus (SIV) and its effects, though it is not known why.[19]

African green monkeys (also called vervets, genus Chlorocebus) in African populations are heavily infected with SIVagm,[27][28] while the virus is absent in the founder isolate vervet populations in the Caribbean.[29] The prevalence of SIV infection in African populations ranges 78-90% in adult females and 36-57% in adult males, while SIV infection is rare in immature individuals.[28][27] SIV infected vervets in the wild do not develop chronic immune activation or microbial translocation (assessed by sCD14 as a surrogate biomarker). During natural SIV infection, the gut microbiome showed a significant increase in microbial diversity, a decrease in Proteobacteria/Succinivibrio and an increase of Veillonella, and a decrease in genes involved in pathways of microbial invasion, and partial reversibility of acute infection-related shifts in microbial abundance.[30] The pattern of natural selection in the monkey genome in genes involved in HIV responses and those regulated in response to experimental SIV infection in monkeys, but not macaques, suggests a natural adaptation to SIV in Chlorocebus monkeys in Africa.[31]

In 2012, researchers reported that initial infection of rhesus monkeys by neutralization-resistant SIV strains[32] could be partially prevented through use of an anti-SIV_SME543 vaccine obligately including Env protein antigens.[33]

In 2013, a study by a group of authors reported on successful testing of a vaccine containing SIV protein-expressing rhesus cytomegalovirus vector. Approximately 50% of vaccinated rhesus macaques manifested durable, aviraemic control of infection with the highly pathogenic strain SIVmac239.[34]

• HIV, the human version of SIV which causes AIDS
• Positive-sense single-stranded RNA virus, a classification which includes SIV
• Zoonosis and Origin of AIDS, transmission from other primates to humans
• List of zoonotic primate viruses
• Other simian exogenous retroviruses: simian-T-lymphotropic virus, simian retrovirus type D, gibbon-ape leukemia virus, simian foamy virus, simian sarcoma virus
• Related viruses also cause disease in other mammals: sheep, goats, cats, cattle, horses
• SV40 is another virus that came from simians and into human populations in the mid twentieth century.

• "HIV origin 'found in wild chimps'" BBC News article
• Peeters et al.: "Risk to Human Health from a Plethora of Simian Immunodeficiency Viruses in Primate Bushmeat", Emerging Infectious Diseases, Vol 8, No 5, May 2002. Contains a picture of the relationship among the various SIV/HIV strains.

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• Description of SIV, including links to subspecies and sequence data, from the International Committee on Taxonomy of Viruses