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Journal article
CD4 receptor diversity in chimpanzees protects against SIV infection
Proceedings of the National Academy of Sciences - PNAS, v 116(8), pp 3229-3238
19 Feb 2019
PMID: 30718403
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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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Details
- Title
- CD4 receptor diversity in chimpanzees protects against SIV infection
- Creators
- Frederic Bibollet-Ruche - University of PennsylvaniaRonnie M Russell - University of PennsylvaniaWeimin Liu - University of PennsylvaniaGuillaume B E Stewart-Jones - Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892Scott Sherrill-Mix - University of PennsylvaniaYingying Li - University of PennsylvaniaGerald H Learn - University of PennsylvaniaAndrew G Smith - University of PennsylvaniaMarcos V P Gondim - University of PennsylvaniaLindsey J Plenderleith - University of EdinburghJulie M Decker - University of Alabama at BirminghamJuliet L Easlick - University of Alabama at BirminghamKatherine S Wetzel - University of PennsylvaniaRonald G Collman - University of PennsylvaniaShilei Ding - University of MontrealAndrés Finzi - University of MontrealAhidjo Ayouba - Recherche Translationnelle Appliquée au VIH et aux Maladies Infectieuses, Institut de Recherche pour le Développement, University of Montpellier, INSERM, 34090 Montpellier, France.Martine Peeters - Recherche Translationnelle Appliquée au VIH et aux Maladies Infectieuses, Institut de Recherche pour le Développement, University of Montpellier, INSERM, 34090 Montpellier, France.Fabian H Leendertz - Robert Koch InstituteJoost van Schijndel - Max Planck Institute for Evolutionary AnthropologyAnnemarie Goedmakers - Chimbo Foundation, 1011 PW Amsterdam, The Netherlands.Els Ton - Chimbo Foundation, 1011 PW Amsterdam, The Netherlands.Christophe Boesch - Max Planck Institute for Evolutionary AnthropologyHjalmar Kuehl - Max Planck Institute for Evolutionary AnthropologyMimi Arandjelovic - Max Planck Institute for Evolutionary AnthropologyPaula Dieguez - Max Planck Institute for Evolutionary AnthropologyMizuki Murai - Max Planck Institute for Evolutionary AnthropologyChristelle Colin - Primate ConservationKathelijne Koops - University of ZurichSheri Speede - Sanaga-Yong Chimpanzee Rescue Center, In Defense of Animals-Africa, Portland, OR 97204.Mary K Gonder - Drexel UniversityMartin N Muller - University of New MexicoCrickette M Sanz - Washington University in St. LouisDavid B Morgan - Lincoln Park ZooRebecca Atencia - Tchimpounga Chimpanzee Rehabilitation Center, The Jane Goodall Institute-Congo, BP 1206 Pointe Noire, Republic of Congo.Debby Cox - The Jane Goodall InstituteAlex K Piel - Liverpool John Moores UniversityFiona A Stewart - Liverpool John Moores UniversityJean-Bosco N Ndjango - Université de KisanganiDeus Mjungu - The Jane Goodall InstituteElizabeth V Lonsdorf - Franklin & Marshall CollegeAnne E Pusey - Duke UniversityPeter D Kwong - Vaccine Research CenterPaul M Sharp - University of EdinburghGeorge M Shaw - University of PennsylvaniaBeatrice H Hahn - University of Pennsylvania
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 116(8), pp 3229-3238
- Publisher
- PNAS
- Grant note
- R37 AI050529 / NIAID NIH HHS R01 AI131331 / NIAID NIH HHS P01 AI131251 / NIAID NIH HHS R01 AI091595 / NIAID NIH HHS UM1 AI100645 / NIAID NIH HHS P51 RR013986 / NCRR NIH HHS R01 AI050529 / NIAID NIH HHS R37 AI150590 / NIAID NIH HHS T32 AI007632 / NIAID NIH HHS P51 OD011133 / NIH HHS UM1 AI126620 / NIAID NIH HHS P30 AI045008 / NIAID NIH HHS P51 RR000165 / NCRR NIH HHS UM1 AI144371 / NIAID NIH HHS 352417 / CIHR R56 AI091516 / NIAID NIH HHS R01 AI120810 / NIAID NIH HHS R61 AI133696 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000459074400065
- Scopus ID
- 2-s2.0-85061864266
- Other Identifier
- 991019168264104721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Virology