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Significance HIV-1 arose following the cross-species transmission of a simian immunodeficiency virus of chimpanzees (SIVcpz) to humans. In this study, we looked at genetic diversity in chimpanzee CD4, which encodes the main receptor for both HIV and SIVcpz. We identified multiple CD4 alleles circulating in chimpanzee populations, some of which impede cellular entry of HIV-1 and SIVcpz. We demonstrate that some chimpanzees would be significantly protected from virus infection because their CD4 protein is modified by the addition of glycans to the virus binding surface. These glycans create a shield that protects the receptor from being engaged by viruses, demonstrating a powerful form of host resistance against deadly primate lentiviruses.

A glycan shield on chimpanzee CD4 protects against infection by primate lentiviruses (HIV/SIV)