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Simian immunodeficiency virus
Virus classification
(unranked):	Virus
Phylum:	incertae sedis
Class:	incertae sedis
Order:	Ortervirales
Family:	Retroviridae
Genus:	Lentivirus
Species:	Simian immunodeficiency virus

Simian immunodeficiency virus (SIVs) is a species of retrovirus that cause persistent infections in at least 45 species of African non-human primates.^[1][2] Based on analysis of strains found in four species of monkeys from Bioko Island, which was isolated from the mainland by rising sea levels about 11,000 years ago, it has been concluded that SIV has been present in monkeys and apes for at least 32,000 years, and probably much longer.^[3][4]

Virus strains from two of these primate species, SIVsmm in sooty mangabeys and SIVcpz in chimpanzees, are believed to have crossed the species barrier into humans, resulting in HIV-2 and HIV-1 respectively, the two human immunodeficiency viruses. The most likely route of transmission of HIV-1 to humans involves contact with the blood of chimps that are often hunted for bushmeat in Africa.^[3] It is theorized SIV may have previously crossed the species barrier into human hosts multiple times throughout history, but it was not until recently, after the advent of modern transportation and global commuterism, that it finally took hold, spreading beyond localized decimations of a few individuals or single small tribal populations.

Unlike HIV-1 and HIV-2 infections in humans, SIV infections in their natural African simian non-human hosts appear in many cases to be non-pathogenic due to evolutionary adaptation of the hosts to the virus. Extensive studies in sooty mangabeys have established that SIVsmm infection does not cause any disease in these African primates, despite high levels of circulating virus. However, if the virus infects an Asian or Indian rhesus macaque, these non-African simian primates will also develop simian AIDS (SAIDS), as they, like humans (despite being an African-origin simian primate species), have not had a prolonged history with the virus.^[5] A recent^[when?] study of SIVcpz in wild living chimpanzees suggests that infected chimpanzees experience an AIDS-like illness similar to HIV-1 infected humans. The later stages of SIV infection turn into SAIDS, much as HIV infection turns into AIDS.

Taxonomy

The ICTVdB code of SIV is 61.0.6.5.003.^[6]

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). The order to which family retroviridae belongs is not specified. The taxonomic relationship between RNA retroviruses and other RNA viruses and DNA viruses has not been specified. SIV retroviruses are in group vi (positive-sense single-stranded retroviruses) of the Baltimore classification system.

Strains

While human immunodeficiency virus has a limited number of subtypes, SIV is now known to infect a few dozen species of non-human primates, and distinct strains are often associated with each species, or with a set of closely related species. The thus far categorized ~40 strains are divided into 5 distinct groups and one subgroup:

• i) HIV-1, SIVcpz (chimpanzee), SIVgor (gorilla), SIVrcm (red-capped mangabey), SIVagi (agile mangabey), SIVmnd 2 (mandrill), SIVdrl (drill monkey)


• ii) HIV-2, SIVsmm (sooty mangabey), SIVmac (rhesus macaque), SIVmne (pig-tailed macaque), SIVstm (stump-tailed macaque)


• iii) SIVagm[generic] (African green monkeys): SIVsab, SIVver, SIVgri (grivet monkey, SIVtan (tantalus monkey)


• iv) SIVmnd 1 (mandrill), SIVlho (L'hoest's monkey), SIVsun (sun-tailed monkey), SIVprg (Preuss's guenon), SIVwrc (western red colobus), SIVolc (olive colobus), SIVkrc (Kibale red colobus), SIVtrc (Tshuapa red colobus)


• v) SIVsyk (Sykes' monkey), SIVdeb (De Brazza's monkey), SIVden (Dent's mona monkey), SIVwol (Wolf's mona monkey), SIVgsn/SIVmon/SIVmus 1/SIVmus 2 clade, SIVtal (northern talapoin), SIVasc (red-tailed guenon), SIVbkm (black mangabey), SIVreg[formerly SIVery] (red-eared guenon), SIVblu (blue monkey)
  
  • vi) SIVcol (colobus guereza), SIVkcol 1 (black-and-white colobus), SIVkcol 2, SIVblc (formerly SIVbcm) (black colobus),

History

Immunodeficiency resembling human AIDS was reported in captive monkeys in the United States beginning in 1983.^[12][13][14] SIV was isolated in 1985 from some of these animals, captive rhesus macaques suffering from simian AIDS (SAIDS).^[13] 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).^{[citation needed]}

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.^[15]

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.^{[16][unreliable source?]} 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.^{[17][unreliable source?]}

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.

Virology

Structure and genome

The SIV virion is a spherical to pleomorphic glycoprotein envelope 110-120 nm enclosing a 110x50nm truncated cone or wedge-shaped (occasionally rod) capsid containing a dimeric pair of positive-sense single-stranded RNA genome.

Genome

• coding regions

Proteome

• genes: env, gag, pol, tat, rev, nef, vpr, vif, vpu/vpx
  


• Structural proteins

 (envelope): SU, TM,(gag): MA, CA, NC

• Enzymes

 RT, PR, IN

• Gene regulators

 Tat, Rev

• Accessory proteins

 Nef, Vpr, Vpx, Vif

Tropism

Differences in species specificity of SIV and related retroviruses may be partly explained by variants of the protein TRIM5α in humans and non-human primate species. This intracellular protein recognizes the capsid of various retroviruses and blocks their reproduction. Other proteins such as APOBEC3G/3F that exerts antiretroviral immune activity, may also be important in restricting cross-species transmission.^[18]

Replication

• Attachment


• Penetration


• Uncoating


• Replication
  
  • reverse transcription

 +ssRNA → -ssDNA → dsDNA → +ssRNA (viral genome)
 → +ssmRNA → viral protein

• • integration
  
  
  • latency
  
  
  • cleavage
  
  
  • protein synthesis
  
  
  • Assembly
  
  


• Budding


• Maturation

Quasispecies

The speed and transcription inaccuracies of RNA viruses give rise to antigenically distinct varieties in a single host animal. These quasispecies don't necessarily give rise to population-wide new organisms. The rate of proliferation of quasispecies has significant implication for host immune control, and therefore virulence of the organism.

Pathogenesis

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.

Epidemiology

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.^[19][20]Bonobos appear to avoid simian immunodeficiency virus (SIV) and its effects, though it is not known why.^[21]

Vaccine research

SHIV, a virus combining parts of the HIV and SIV genomes, was created for various research purposes, including analyzing how different parts of the virus respond to different antimicrobial drugs and vaccines.^[22]

In 2012, researchers reported that initial infection of rhesus monkeys by neutralization-resistant SIV strains^[23] could be partially prevented through use of an anti-SIV_SME543 vaccine obligately including Env protein antigens.^[24]

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.^[25]

See also

• 
  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
  

Further reading

• 
  "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.

References

External links

Wikimedia Commons has media related to Simian immunodeficiency virus (SIV) protease.

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