Simian immunodeficiency virus

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Simian immunodeficiency virus
SIV virion in 3D.jpg
SIV virion model obtained with cryo-electron microscopy scanning
Virus classification e
(unranked): Virus
Realm: Riboviria
Kingdom: Pararnavirae
Phylum: Artverviricota
Class: Revtraviricetes
Order: Ortervirales
Family: Retroviridae
Genus: Lentivirus
Species:
Simian immunodeficiency virus

Simian immunodeficiency virus (SIV) 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. Four subtypes of HIV-1 (M, N, O, and P) likely arose through four separate transmissions of SIV to humans, and the resulting HIV-1 group M strain most commonly infects people worldwide.[5][6] Therefore, it is theorized that 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.[7] 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 develop into SAIDS, much like how HIV infection develops into AIDS.

Taxonomy[]

The ICTVdB code of SIV is 61.0.6.5.003.[8]

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:

 
 
 grp i 
 
 
 
 

HIV-1

 
 

cpzPtt

 
 
 

gor

 
 
 

cpzPts

 
 
 
 
 

drl

 
 

mnd2

 
 
 
 

rcm

 
 

agi

 
 
 
 
 grp ii 
 
 
 

HIV-2

 
 

mac

 
 
 

mne

 
 

stm

 
 
 

smm

 
 
 
 grp iii/agm 
 
 
 

gri

 
 

ver

 
 
 

tan

 
 
 

sab

 
 
 grp iv 
 
 
 
 

lho

 
 

sun

 
 
 

prg

 
 
 

mnd1

 
 
 
 
 

wrc

 
 

olc

 
 
 
 

trc

 
 

krc

 
 
 
 
 
 grp v 
 
 
 
 
 
 

gsn

 
 
 

mus2

 
 (grp vi) 
 
 
 

col

 
 

kcol1

 
 
 

kcol2

 
 
 

blc

 
 
 
 
 

mon

 
 

mus1

 
 
 

reg

 
 
 
 

tal

 
 
 

asc

 
 

bkm

 
 
 
 
 
 

deb

 
 

blu

 
 
 
 

den

 
 

syk

 
 
 

wol

 
 
 
 
 
Phylogenetic relations between simian immunodeficiency viruses (SIVs)[9][10][11][12][13]

History[]

Immunodeficiency resembling human AIDS was reported in captive monkeys in the United States beginning in 1983.[14][15][16] SIV was isolated in 1985 from some of these animals, captive rhesus macaques suffering from simian AIDS (SAIDS).[15] 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.[17] 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.[18][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.[19][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[]

Further information: Structure and genome of HIV § Genome organization
  • 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.[20]

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[]

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.

Epidemiology[]

strain lineage host binomial disease
HIV-1 SIVcpz humans H. sapiens AIDS
HIV-2 SIVsmm humans H. sapiens AIDS
SIVcpz SIVrcm/SIVgsn Chimpanzee P. Troglodytes SAIDS
SIVgor SIVcpz Gorilla G. gorilla ( - )
SIVsmm Sooty mangabey ( - )

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.[21][22] Bonobos appear to avoid simian immunodeficiency virus (SIV) and its effects, though it is not known why.[17]

African green monkeys (also called vervets, genus Chlorocebus) in African populations are heavily infected with SIVagm,[23][24] while the virus is absent in the founder isolate vervet populations in the Caribbean.[25] 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.[24][23] 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.[26] 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.[27]

Vaccine research[]

In 2012, researchers reported that initial infection of rhesus monkeys by neutralization-resistant SIV strains[28] could be partially prevented through use of an anti-SIVSME543 vaccine obligately including Env protein antigens.[29]

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.[30]

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, , 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.

References[]

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  3. ^ (September 16, 2010). "Precursor to H.I.V. Was in Monkeys for Millennia". New York Times. Retrieved 2010-09-17. In a discovery that sheds new light on the history of AIDS, scientists have found evidence that the ancestor to the virus that causes the disease has been in monkeys and apes for at least 32,000 years — not just a few hundred years, as had been previously thought. ... That means humans have presumably been exposed many times to S.I.V., the simian immunodeficiency virus, because people have been hunting monkeys for millenniums, risking infection every time they butcher one for food.
  4. ^ Worobey M, Telfer P, Souquière S, Hunter M, Coleman CA, Metzger MJ, et al. (September 2010). "Island biogeography reveals the deep history of SIV". Science. 329 (5998): 1487. Bibcode:2010Sci...329.1487W. doi:10.1126/science.1193550. PMID 20847261. S2CID 37803712..
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  8. ^ ICTV database entry: 61.0.6.5.003
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  13. ^ Lauck M, Switzer WM, Sibley SD, Hyeroba D, Tumukunde A, Weny G, et al. (October 2013). "Discovery and full genome characterization of two highly divergent simian immunodeficiency viruses infecting black-and-white colobus monkeys (Colobus guereza) in Kibale National Park, Uganda". Retrovirology. 10: 107. doi:10.1186/1742-4690-10-107. PMC 4016034. PMID 24139306.
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  16. ^ King NW, Hunt RD, Letvin NL (December 1983). "Histopathologic changes in macaques with an acquired immunodeficiency syndrome (AIDS)". The American Journal of Pathology. 113 (3): 382–8. PMC 1916356. PMID 6316791.
  17. ^ Jump up to: a b Sharp PM, Shaw GM, Hahn BH (April 2005). "Simian immunodeficiency virus infection of chimpanzees". Journal of Virology. 79 (7): 3891–902. doi:10.1128/JVI.79.7.3891-3902.2005. PMC 1061584. PMID 15767392.
  18. ^ McNeil Jr DG (17 September 2010). "Precursor to H.I.V. Was in Monkeys for Millenniums". The New York Times. Retrieved 17 September 2010.
  19. ^ "HIV precursor in monkeys ancient: study". CBC News. 17 September 2010. Archived from the original on March 25, 2013. Retrieved 17 September 2010.
  20. ^ Heeney JL, Dalgleish AG, Weiss RA (July 2006). "Origins of HIV and the evolution of resistance to AIDS". Science. 313 (5786): 462–6. Bibcode:2006Sci...313..462H. doi:10.1126/science.1123016. PMID 16873637. S2CID 27673160.
  21. ^ Chimpanzees Do Die From Simian AIDS, Study Finds by Lawrence K. Altman Chimpanzees Do Die from Simian AIDS, Study Finds
  22. ^ Keele BF, Jones JH, Terio KA, Estes JD, Rudicell RS, Wilson ML, et al. (July 2009). "Increased mortality and AIDS-like immunopathology in wild chimpanzees infected with SIVcpz". Nature. 460 (7254): 515–9. Bibcode:2009Natur.460..515K. doi:10.1038/nature08200. PMC 2872475. PMID 19626114.
  23. ^ Jump up to: a b Ma D, Jasinska A, Kristoff J, Grobler JP, Turner T, Jung Y, et al. (January 2013). "SIVagm infection in wild African green monkeys from South Africa: epidemiology, natural history, and evolutionary considerations". PLOS Pathogens. 9 (1): e1003011. doi:10.1371/journal.ppat.1003011. PMC 3547836. PMID 23349627.
  24. ^ Jump up to: a b Ma D, Jasinska AJ, Feyertag F, Wijewardana V, Kristoff J, He T, et al. (May 2014). "Factors associated with siman immunodeficiency virus transmission in a natural African nonhuman primate host in the wild". Journal of Virology. 88 (10): 5687–705. doi:10.1128/JVI.03606-13. PMC 4019088. PMID 24623416.
  25. ^ Kapusinszky B, Mulvaney U, Jasinska AJ, Deng X, Freimer N, Delwart E (August 2015). "Local Virus Extinctions following a Host Population Bottleneck". Journal of Virology. 89 (16): 8152–61. doi:10.1128/jvi.00671-15. PMC 4524239. PMID 26018153.
  26. ^ Jasinska AJ, Dong TS, Lagishetty V, Katzka W, Jacobs JP, Schmitt C, et al. (2020-11-06). "Shifts in microbial diversity, composition, and functionality in the gut and genital microbiome during a natural SIV infection in vervet monkeys". Microbiome. 8 (1): 154. doi:10.1186/s40168-020-00928-4. PMC 7648414. PMID 33158452.
  27. ^ Svardal H, Jasinska AJ, Apetrei C, Coppola G, Huang Y, Schmitt CA, et al. (December 2017). "Ancient hybridization and strong adaptation to viruses across African vervet monkey populations". Nature Genetics. 49 (12): 1705–1713. doi:10.1038/ng.3980. PMC 5709169. PMID 29083404.
  28. ^ "Neutralization-resistant" refers to strains which are not able to be neutralized by the native immune response due to compensating mutation; see HIV-1 related information.
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  30. ^ Hansen SG, Piatak M, Ventura AB, Hughes CM, Gilbride RM, Ford JC, et al. (October 2013). "Immune clearance of highly pathogenic SIV infection". Nature. 502 (7469): 100–4. Bibcode:2013Natur.502..100H. doi:10.1038/nature12519. PMC 3849456. PMID 24025770.

Further reading[]

External links[]

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