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 OOjs UI icon edit-ltr.svg
(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 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]

Contents

Virus strains from three of these primate species, SIVsmm in sooty mangabeys, SIVgor in gorillas and SIVcpz in chimpanzees, are believed to have crossed the species barrier into humans, resulting in HIV-2 and HIV-1 respectively, the two HIV viruses. The most likely route of transmission of HIV-1 to humans involves contact with the blood of chimps and gorillas 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 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 primates, despite high levels of circulating virus. Regulation of the activity CCR5 coreceptor is one of the natural strategies to avoid disease in some natural host species of SIV. [7]

Unlike SIVsmm infection in sooty mangabeys, 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 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.

Strains

 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) [10] [11] [12] [13] [14]

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: [10]

In addition to the subgroups defined for extent SIVs, two endogenous SIVs are found in prosimian lemurs. These paleo-SIVs form a basal branch relative to extant SIVs. [15]

History

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).[ 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. [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]

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.[ citation needed ]

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. [23]

Replication

 +ssRNA → -ssDNA → dsDNA → +ssRNA (viral genome)                          → +ssmRNA → viral protein
  • integration
  • latency
  • cleavage
  • protein synthesis
  • Assembly

Quasispecies

The speed and transcription inaccuracies of RNA viruses give rise to antigenically distinct varieties in a single host animal. These quasispecies do not 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.[ citation needed ]

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. Mapping SHIV infection in the body, 2018 - Wellcome Photography Prize 2019 (bottom right, cropped).jpg
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.[ citation needed ]

SIV/HIV infection similarities and differences

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

The differences (what happens in nonhuman primates):

Epidemiology

strainlineagehostbinomialdisease
HIV-1SIVcpzhumansH. sapiens AIDS
HIV-2SIVsmmhumansH. sapiens AIDS
SIVcpzSIVrcm/SIVgsnChimpanzeeP. TroglodytesSAIDS
SIVgorSIVcpzGorillaG. gorilla( - )
SIVsmmSooty 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. [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]

Vaccine research

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-SIVSME543 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]

See also

Related Research Articles

<span class="mw-page-title-main">HIV</span> Human retrovirus, cause of AIDS

The human immunodeficiency viruses (HIV) are two species of Lentivirus that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Without treatment, average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype.

<span class="mw-page-title-main">Bushmeat</span> Meat hunted in tropical forests

Bushmeat is meat from wildlife species that are hunted for human consumption. Bushmeat represents a primary source of animal protein and a cash-earning commodity for inhabitants of humid tropical forest regions in Africa, Latin America and Asia. Bushmeat is an important food resource in poor, rural communities.

The oral polio vaccine (OPV) AIDS hypothesis is a now-discredited hypothesis that the AIDS pandemic originated from live polio vaccines prepared in chimpanzee tissue cultures, accidentally contaminated with simian immunodeficiency virus and then administered to up to one million Africans between 1957 and 1960 in experimental mass vaccination campaigns.

<span class="mw-page-title-main">TRIM5alpha</span>

Tripartite motif-containing protein 5 also known as RING finger protein 88 is a protein that in humans is encoded by the TRIM5 gene. The alpha isoform of this protein, TRIM5α, is a retrovirus restriction factor, which mediates a species-specific early block to retrovirus infection.

<i>Chlorocebus</i> Genus of Old World monkeys

Chlorocebus is a genus of medium-sized primates from the family of Old World monkeys. Six species are currently recognized, although some people classify them all as a single species with numerous subspecies. Either way, they make up the entirety of the genus Chlorocebus.

<span class="mw-page-title-main">Sooty mangabey</span> Species of mammal

The sooty mangabey is an Old World monkey found in forests from Senegal in a margin along the coast down to the Ivory Coast.

<span class="mw-page-title-main">History of HIV/AIDS</span> Epidemiological history

AIDS is caused by a human immunodeficiency virus (HIV), which originated in non-human primates in Central and West Africa. While various sub-groups of the virus acquired human infectivity at different times, the present pandemic had its origins in the emergence of one specific strain – HIV-1 subgroup M – in Léopoldville in the Belgian Congo in the 1920s.

Simian foamy virus (SFV) is a species of the genus Spumavirus that belongs to the family of Retroviridae. It has been identified in a wide variety of primates, including prosimians, New World and Old World monkeys, as well as apes, and each species has been shown to harbor a unique (species-specific) strain of SFV, including African green monkeys, baboons, macaques, and chimpanzees. As it is related to the more well-known retrovirus human immunodeficiency virus (HIV), its discovery in primates has led to some speculation that HIV may have been spread to the human species in Africa through contact with blood from apes, monkeys, and other primates, most likely through bushmeat-hunting practices.

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<span class="mw-page-title-main">CXCR6</span>

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<span class="mw-page-title-main">Subtypes of HIV</span> Variants of the human immunodeficiency virus

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<span class="mw-page-title-main">Agile mangabey</span> Species of Old World monkey

The agile mangabey is an Old World monkey of the white-eyelid mangabey group found in swampy forests of Central Africa in Equatorial Guinea, Cameroon, Gabon, Central African Republic, Republic of Congo, and DR Congo. Until 1978, it was considered a subspecies of the Tana River mangabey. More recently, the golden-bellied mangabey has been considered a separate species instead of a subspecies of the agile mangabey.

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<span class="mw-page-title-main">Nef (protein)</span>

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<span class="mw-page-title-main">Host switch</span> Evolutionary change of the host specificity of a parasite or pathogen

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References

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  25. ↑ Chimpanzees Do Die From Simian AIDS, Study Finds by Lawrence K. Altman Chimpanzees Do Die from Simian AIDS, Study Finds
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  27. 1 2 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.
  28. 1 2 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): 5687–5705. doi:10.1128/JVI.03606-13. PMC   4019088 . PMID   24623416.
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  32. ↑ "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.
  33. ↑ Barouch DH, Liu J, Li H, Maxfield LF, Abbink P, Lynch DM, et al. (January 2012). "Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys". Nature. 482 (7383): 89–93. Bibcode:2012Natur.482...89B. doi:10.1038/nature10766. PMC   3271177 . PMID   22217938.
  34. ↑ 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): 100–104. Bibcode:2013Natur.502..100H. doi:10.1038/nature12519. PMC   3849456 . PMID   24025770.

Further reading

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