| Title: |
CD4 receptor diversity in chimpanzees protects against SIV infection |
| Authors: |
Bibollet-Ruche, Frederic; Russell, Ronnie; Liu, Weimin; Stewart-Jones, Guillaume; Sherrill-Mix, Scott; Li, Yingying; Learn, Gerald; Smith, Andrew; Gondim, Marcos; Plenderleith, Lindsey; Decker, Julie; Easlick, Juliet; Wetzel, Katherine; Collman, Ronald; Ding, Shilei; Finzi, Andrés; Ayouba, Ahidjo; Peeters, Martine; Leendertz, Fabian; van Schijndel, Joost; Goedmakers, Annemarie; Ton, Els; Boesch, Christophe; Kuehl, Hjalmar; Arandjelovic, Mimi; Dieguez, Paula; Murai, Mizuki; Colin, Christelle; Koops, Kathelijne; Speede, Sheri; Gonder, Mary; Muller, Martin; Sanz, Crickette; Morgan, David; Atencia, Rebecca; Cox, Debby; Piel, Alex; Stewart, Fiona; Ndjango, Jean-Bosco; Mjungu, Deus; Lonsdorf, Elizabeth; Pusey, Anne; Kwong, Peter; Sharp, Paul; Shaw, George; Hahn, Beatrice |
| Contributors: |
University of Pennsylvania Philadelphia; Shanxi University (SXU); The Wellcome Trust Centre for Human Genetics Oxford; University of Oxford; University of Alabama Birmingham (UAB); DIAMOND Light source; Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM); Centre Hospitalier de l'Université de Montréal (CHUM); Université de Montréal (UdeM)-Université de Montréal (UdeM); Université de Montréal (UdeM); Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI); Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I (UY1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Cheikh Anta Diop de Dakar Sénégal (UCAD); Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I (UY1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Cheikh Anta Diop de Dakar Sénégal (UCAD); Robert Koch Institute Berlin (RKI); Helmholtz Institut für One Health Greifswald, Germany (HIOH) |
| Source: |
ISSN: 0027-8424. |
| Publisher Information: |
CCSD; National Academy of Sciences |
| Publication Year: |
2019 |
| Collection: |
Université de Montpellier: HAL |
| Subject Terms: |
CD4; SIV; chimpanzee; envelope glycoprotein; glycan restriction; MESH: Animals; MESH: CD4 Antigens; MESH: Simian Immunodeficiency Virus; MESH: Viral Envelope Proteins; MESH: CD4-Positive T-Lymphocytes; MESH: Evolution; Molecular; MESH: Genetic Variation; MESH: HIV; MESH: Humans; MESH: Pan troglodytes; MESH: Polysaccharides; MESH: Simian Acquired Immunodeficiency Syndrome; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/30718403; PUBMED: 30718403; PUBMEDCENTRAL: PMC6386711 |
| DOI: |
10.1073/pnas.1821197116 |
| Availability: |
https://hal.science/hal-05074843; https://hal.science/hal-05074843v1/document; https://hal.science/hal-05074843v1/file/pnas.201821197.pdf; https://doi.org/10.1073/pnas.1821197116 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.4CDF07AF |
| Database: |
BASE |