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CD4 receptor diversity represents an ancient protection mechanism against primate lentiviruses

2021; National Academy of Sciences; Volume: 118; Issue: 13 Linguagem: Inglês

10.1073/pnas.2025914118

1091-6490

Ronnie M. Russell, Frédéric Bibollet‐Ruche, Weimin Liu, Scott Sherrill-Mix, Yingying Li, Andrew Connell, Dorothy E. Loy, Stephanie Trimboli, Andrew G. Smith, Alexa N. Avitto, Marcos V. P. Gondim, Lindsey J. Plenderleith, Katherine S. Wetzel, Ronald G. Collman, Ahidjo Ayouba, Amandine Esteban, Martine Peeters, W Kohler, Richard A. Miller, Sandrine François-Souquiere, William M. Switzer, Vanessa M. Hirsch, Preston A. Marx, A. Piel, Fiona A. Stewart, Alexander V. Georgiev, Volker Sommer, Paco Bertolani, John Hart, Térese B. Hart, George M. Shaw, Paul M. Sharp, Beatrice H. Hahn,

T-cell and B-cell Immunology

Significance The CD4 protein of primates has undergone rapid diversification, but the reasons for this remain unknown. Here we show that within-species diversity of the HIV/simian immunodeficiency virus (SIV) envelope (Env) binding (D1) domain is common among African primate species, and that these polymorphisms can inhibit SIV Env-mediated cell entry. Amino acid replacements in the D1 domain changed putative Env contact residues as well as potential N -linked glycosylation sites in many species, with evidence for parallel evolution and trans-specific polymorphism. These data suggest that the primate CD4 receptor is under long-term balancing selection and that this diversification has been the result of a coevolutionary arms race between primate lentiviruses and their hosts.