AIDS in chimpanzees: the role of MHC genes

Groot, Natasja G. de; Heijmans, Corinne M. C.; Bontrop, Ronald E.

doi:10.1007/s00251-017-1006-6

Cited by 11 publications

(13 citation statements)

References 98 publications

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“…Still another possibility is that some, or all, of the CD4 polymorphisms were selected by unrelated pathogen(s) (53, 54). However, others have independently implicated an ancient SIV infection to explain the skewed MHC class I repertoires of chimpanzees and bonobos, which include allotypes that resemble AIDS-protective human HLA alleles (55). Thus, there are several lines of evidence to suggest that different SIVs, both extant and extinct, have shaped the evolution of the chimpanzee CD4.…”

Section: Discussionmentioning

confidence: 99%

CD4 receptor diversity in chimpanzees protects against SIV infection

Bibollet-Ruche

Russell

Liu

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Human and simian immunodeficiency viruses (HIV/SIVs) use CD4 as the primary receptor to enter target cells. Here, we show that the chimpanzee CD4 is highly polymorphic, with nine coding variants present in wild populations, and that this diversity interferes with SIV envelope (Env)–CD4 interactions. Testing the replication fitness of SIVcpz strains in CD4+ T cells from captive chimpanzees, we found that certain viruses were unable to infect cells from certain hosts. These differences were recapitulated in CD4 transfection assays, which revealed a strong association between CD4 genotypes and SIVcpz infection phenotypes. The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles. In silico modeling and site-directed mutagenesis identified charged residues at the CD4–Env interface and clashes between CD4- and Env-encoded glycans as mechanisms of inhibition. CD4 polymorphisms also reduced Env-mediated cell entry of monkey SIVs, which was dependent on at least one D1 domain glycan. CD4 allele frequencies varied among wild chimpanzees, with high diversity in all but the western subspecies, which appeared to have undergone a selective sweep. One allele was associated with lower SIVcpz prevalence rates in the wild. These results indicate that substitutions in the D1 domain of the chimpanzee CD4 can prevent SIV cell entry. Although some SIVcpz strains have adapted to utilize these variants, CD4 diversity is maintained, protecting chimpanzees against infection with SIVcpz and other SIVs to which they are exposed.

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Section: Discussionmentioning

confidence: 99%

CD4 receptor diversity in chimpanzees protects against SIV infection

Bibollet-Ruche

Russell

Liu

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…Concerning the importance of MHC genes to the immune system and potential fitness consequences, selective forces by different pathogens may be the most cogent explanation. For example, the reduced MHC diversity in chimpanzees and bonobos as compared to humans was speculated to be the outcome of a selective sweep mediated by SIV (simian immunodeficiency virus) or another virus in the ancestor of chimpanzee and bonobos [58–61]. Importantly, the different chimpanzee subspecies have different demographic histories and effective population sizes [14–17].…”

Section: Discussionmentioning

confidence: 99%

Reduced bonobo MHC class I diversity predicts a reduced viral peptide binding ability compared to chimpanzees

Maibach

Vigilant

2019

BMC Evol Biol

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BackgroundThe highly polymorphic genes of the major histocompatibility complex (MHC) class I are involved in defense against viruses and other intracellular pathogens. Although several studies found reduced MHC class I diversity in bonobos in comparison to the closely related chimpanzee, it is unclear if this lower diversity also influences the functional ability of MHC class I molecules in bonobos. Here, we use a bioinformatic approach to analyze the viral peptide binding ability of all published bonobo MHC class I molecules (n = 58) in comparison to all published chimpanzee MHC class I molecules (n = 161) for the class I loci A, B, C and A-like.ResultsWe examined the peptide binding ability of all 219 different MHC class I molecules to 5,788,712 peptides derived from 1432 different primate viruses and analyzed the percentage of bound peptides and the overlap of the peptide binding repertoires of the two species. We conducted multiple levels of analysis on the “species”-, “population”- and “individual”-level to account for the characterization of MHC variation in a larger number of chimpanzees and their broader geographic distribution. We found a lower percentage of bound peptides in bonobos at the B locus in the “population”-level comparison and at the B and C loci in the “individual”-level comparison. Furthermore, we found evidence of a limited peptide binding repertoire in bonobos by tree-based visualization of functional clustering of MHC molecules, as well as an analysis of peptides bound by both species.ConclusionOur results suggest a reduced MHC class I viral peptide binding ability at the B and C loci in bonobos compared to chimpanzees. The effects of this finding on the immune defense against viruses in wild living bonobos are unclear. However, special caution is needed to prevent introduction and spread of new viruses to bonobos, as their defensive ability to cope with new viruses could be limited compared to chimpanzees.Electronic supplementary materialThe online version of this article (10.1186/s12862-019-1352-0) contains supplementary material, which is available to authorized users.

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“…Pie charts illustrating the MHC class I intron 2 lineage distribution in human (HLA), chimpanzee (Patr) and bonobo (Papa) (adapted from Groot, Heijmans, & Bontrop, 2017). The influence of selection on the classical MHC class I genes has been studied by comparing intron 2 variation in humans and chimpanzee alleles in two well‐defined populations (de Groot et al., 2002).…”

Section: Mhc Polymorphism: Humans Versus Chimpanzees and Rhesus Macaquesmentioning

confidence: 99%

“…One wonders what may have caused the initial selective sweep. In brief, chimpanzees appear to be relatively resistant to developing AIDS after experimental infection with human immunodeficiency virus type‐1 (HIV‐1) or natural infection with the chimpanzee‐derived simian immunodeficiency virus (SIV cpz ) infection (de Groot, Heijmans, & Bontrop, 2017). In bonobos, infections with HIV‐1/SIV have not been documented (Li et al., 2012).…”

Section: Mhc Polymorphism: Humans Versus Chimpanzees and Rhesus Macaquesmentioning

confidence: 99%

“…In humans, a relative resistance to developing AIDS correlates with the presence of particular HLA allotypes, such as HLA‐B*27/B*57 (Fellay et al., 2007;Goulder & Walker, 2012;Kiepiela et al., 2004). From a functional point of view, the reduced chimpanzee MHC class I repertoire encodes allotypes that have the capability of targeting conserved retroviral elements (Groot, Heijmans, & Bontrop, 2017;de Groot et al., 2010), and act in a way similar to that of the AIDS controlling HLA‐B*27/B*57 allotypes in humans. Hence, the selective sweep in the MHC class I repertoire of chimpanzees was most likely caused by an ancestral retroviral infection that had similarities to HIV‐1 (de Groot et al., 2010).…”

Section: Mhc Polymorphism: Humans Versus Chimpanzees and Rhesus Macaquesmentioning

confidence: 99%

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Comparative genetics of the major histocompatibility complex in humans and nonhuman primates

Heijmans

Groot

Bontrop

2020

Int J Immunogenetics

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The major histocompatibility complex (MHC) is one of the most gene-dense regions of the mammalian genome. Multiple genes within the human MHC (HLA) show extensive polymorphism, and currently, more than 26,000 alleles divided over 39 different genes are known. Nonhuman primate (NHP) species are grouped into great and lesser apes and Old and New World monkeys, and their MHC is studied mostly because of their important role as animal models in preclinical research or in connection with conservation biology purposes. The evolutionary equivalents of many of the HLA genes are present in NHP species, and these genes may also show abundant levels of polymorphism. This review is intended to provide a comprehensive comparison relating to the organization and polymorphism of human and NHP MHC regions. K E Y W O R D Sgenetics, histocompatibility, immunology, molecular biology, nonhuman, polymorphism

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AIDS in chimpanzees: the role of MHC genes

Cited by 11 publications

References 98 publications

CD4 receptor diversity in chimpanzees protects against SIV infection

CD4 receptor diversity in chimpanzees protects against SIV infection

Reduced bonobo MHC class I diversity predicts a reduced viral peptide binding ability compared to chimpanzees

Comparative genetics of the major histocompatibility complex in humans and nonhuman primates

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