The genome of the vervet (<i>Chlorocebus aethiops sabaeus</i>)

Warren, Wesley C.; Jasinska, Anna J.; García-Pérez, Raquel; Svardal, Hannes; Tomlinson, Chad; Rocchi, Mariano; Archidiacono, Nicoletta; Capozzi, Oronzo; Minx, Patrick; Montague, Michæl J.; Kim, Kyung; Hillier, La Deana W.; Kremitzki, Milinn; Graves, Tina; Chiang, Colby; Hughes, Jennifer F.; Tran, Nam K.; Huang, Yu; Ramensky, Vasily; Choi, Oi Wa; Jung, Yoon; Schmitt, Christopher A.; Juretic, Nikoleta; Wasserscheid, Jessica; Turner, Trudy R.; Wiseman, Roger W.; Tuscher, Jennifer J.; Karl, Julie A.; Schmitz, Jörn E.; Zahn, Roland; O’Connor, David H.; Redmond, Eugene; Nisbett, Alex; Jacquelin, Béatrice; Müller‐Trutwin, Michaela; Brenchley, Jason M.; Dione, Michel; Antonio, Martín; Schroth, Gary P.; Kaplan, Jay R.; Jorgensen, Matthew J.; Thomas, Gregg W.C.; Hahn, Matthew W.; Raney, Brian J.; Aken, Bronwen; Nag, Rishi; Schmitz, Juergen; Churakov, Gennady; Noll, Angela; Stanyon, Roscoe; Webb, David; Thibaud‐Nissen, Françoise; Nordborg, Magnus; Marquès‐Bonet, Tomàs; Dewar, Ken; Weinstock, George M.; Wilson, Richard K.; Freimer, Nelson B.

doi:10.1101/gr.192922.115

Cited by 119 publications

(118 citation statements)

References 70 publications

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“…The sequences of most cloned coreceptors were identical to those of the genes described in the recently sequenced sabaeus genome (BioProject accession number PRJNA215854) (40). One exception was CCR2b, which contained a conservative V340A difference.…”

Section: Resultsmentioning

confidence: 93%

CXCR6-Mediated Simian Immunodeficiency Virus SIVagmSab Entry into Sabaeus African Green Monkey Lymphocytes Implicates Widespread Use of Non-CCR5 Pathways in Natural Host Infections

Wetzel

Elliott

et al. 2017

J Virol

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African green monkeys (AGM) and sooty mangabeys (SM) are wellstudied natural hosts of simian immunodeficiency virus (SIV) that do not progress to AIDS when infected with their species-specific viruses. Natural hosts of SIV express very low levels of the canonical entry coreceptor CCR5, and recent studies have shown that CCR5 is dispensable for SIV infection of SM in vivo and that blocking of CCR5 does not prevent ex vivo infection of peripheral blood mononuclear cells (PBMC) from SM or vervet AGM. In both hosts, CXCR6 is an efficient entry pathway in vitro. Here we investigated the use of species-matched CXCR6 and other alternative coreceptors by SIVagmSab, which infects sabaeus AGM. We cloned sabaeus CD4 and 10 candidate coreceptors. Species-matched CXCR6, CCR5, and GPR15 mediated robust entry into transfected cells by pseudotypes carrying SIVagmSab92018ivTF Env, with lower-level entry through GPR1 and APJ. We cloned genetically divergent env genes from the plasma of two wild-infected sabaeus AGM and found similar patterns of coreceptor use. Titration experiments showed that CXCR6 and CCR5 were more efficient than other coreceptors when tested at limiting CD4/coreceptor levels. Finally, blocking of CXCR6 with its ligand CXCL16 significantly inhibited SIVagmSab replication in sabaeus PBMC and had a greater impact than did the CCR5 blocker maraviroc, confirming the use of CXCR6 in primary lymphocyte infection. These data suggest a new paradigm for SIV infection of natural host species, whereby a shared outcome of virus-host coevolution is the use of CXCR6 or other alternative coreceptors for entry, which may direct SIV toward CD4 ϩ T cell subsets and anatomical sites that support viral replication without disrupting immune homeostasis and function.IMPORTANCE Natural hosts of SIV do not progress to AIDS, in stark contrast to pathogenic human immunodeficiency virus type 1 (HIV-1)-human and SIVmacmacaque infections. Identifying how natural hosts avoid immunodeficiency can elucidate key mechanisms of pathogenesis. It is known that despite high viral loads, natural hosts have a low frequency of CD4 ϩ cells expressing the SIV coreceptor CCR5. In this study, we demonstrate the efficient use of the coreceptor CXCR6 by SIVagmSab to infect sabaeus African green monkey lymphocytes. In conjunction with studies of SIVsmm, which infects sooty mangabeys, and SIVagmVer, which infects vervet monkeys, our data suggest a unifying model whereby in natural hosts, in which the CCR5 expression level is low, the use of CXCR6 or other coreceptors to

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Section: Resultsmentioning

confidence: 93%

CXCR6-Mediated Simian Immunodeficiency Virus SIVagmSab Entry into Sabaeus African Green Monkey Lymphocytes Implicates Widespread Use of Non-CCR5 Pathways in Natural Host Infections

Wetzel

Elliott

et al. 2017

J Virol

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“…We then removed all clusters only present in a single species, resulting in 10,967 gene families. We also obtained an ultrametric tree from a previous study and added sooty mangabey based on its divergence time from baboon (TimeTree) 36,37 .…”

Section: Methodsmentioning

confidence: 99%

Sooty mangabey genome sequence provides insight into AIDS resistance in a natural SIV host

Palesch

Bosinger

Tharp

et al. 2018

Nature

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In contrast to infections with human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in macaques, SIV infection of a natural host, sooty mangabeys (Cercocebus atys), is non-pathogenic despite high viraemia1. Here we sequenced and assembled the genome of a captive sooty mangabey. We conducted genome-wide comparative analyses of transcript assemblies from C. atys and AIDS-susceptible species, such as humans and macaques, to identify candidates for host genetic factors that influence susceptibility. We identified several immune-related genes in the genome of C. atys that show substantial sequence divergence from macaques or humans. One of these sequence divergences, a C-terminal frameshift in the toll-like receptor-4 (TLR4) gene of C. atys, is associated with a blunted in vitro response to TLR-4 ligands. In addition, we found a major structural change in exons 3–4 of the immune-regulatory protein intercellular adhesion molecule 2 (ICAM-2); expression of this variant leads to reduced cell surface expression of ICAM-2. These data provide a resource for comparative genomic studies of HIV and/or SIV pathogenesis and may help to elucidate the mechanisms by which SIV-infected sooty mangabeys avoid AIDS.

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“…For example, the lifespan of African green monkeys in captivity ranges between 11 and 13 years (likely an upper limit for their age in the wild as they are heavily preyed upon; Fairbanks and McGuire 1985) with a generation time of ∼8.5 years (Warren et al. ). In contrast, the average human generation time ranges from 26 to 30 years (Moorjani et al.…”

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confidence: 99%

Direct estimate of the spontaneous germ line mutation rate in African green monkeys

Pfeifer

2017

Evolution

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Here, I provide the first direct estimate of the spontaneous mutation rate in an Old World monkey, using a seven individual, three-generation pedigree of African green monkeys. Eight de novo mutations were identified within ∼1.5 Gbp of accessible genome, corresponding to an estimated point mutation rate of 0.94 × 10 per site per generation, suggesting an effective population size of ∼12000 for the species. This estimation represents a significant improvement in our knowledge of the population genetics of the African green monkey, one of the most important nonhuman primate models in biomedical research. Furthermore, by comparing mutation rates in Old World monkeys with the only other direct estimates in primates to date-humans and chimpanzees-it is possible to uniquely address how mutation rates have evolved over longer time scales. While the estimated spontaneous mutation rate for African green monkeys is slightly lower than the rate of 1.2 × 10 per base pair per generation reported in chimpanzees, it is similar to the lower range of rates of 0.96 × 10 -1.28 × 10 per base pair per generation recently estimated from whole genome pedigrees in humans. This result suggests a long-term constraint on mutation rate that is quite different from similar evidence pertaining to recombination rate evolution in primates.

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The genome of the vervet (Chlorocebus aethiops sabaeus)

Cited by 119 publications

References 70 publications

CXCR6-Mediated Simian Immunodeficiency Virus SIVagmSab Entry into Sabaeus African Green Monkey Lymphocytes Implicates Widespread Use of Non-CCR5 Pathways in Natural Host Infections

CXCR6-Mediated Simian Immunodeficiency Virus SIVagmSab Entry into Sabaeus African Green Monkey Lymphocytes Implicates Widespread Use of Non-CCR5 Pathways in Natural Host Infections

Sooty mangabey genome sequence provides insight into AIDS resistance in a natural SIV host

Direct estimate of the spontaneous germ line mutation rate in African green monkeys

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