CypA is a molecular barrier to HIV emergence from Eastern chimpanzees
Year: 2026
Type: preprint
Abstract: Of the two lineages of lentivirus that endemically infect chimpanzees, only one has served as a source of infections in humans. Using HIV-CRISPR screening, we identify factors that limit the replication of lentivirus from Eastern chimpanzees. We find that CypA restricts nonzoonotic Eastern chimpanzee lentivirus due to a unique feature encoded in capsid. The ability of CypA to restrict lentivirus replication is surprising given that CypA is a host factor exploited by HIV to promote its replication. The selective ability of CypA to restrict this virus provides a molecular explanation as to why lentivirus from Eastern Chimpanzees has never been observed to infect humans. Our work has important implications for understanding the origins of HIV-1 and the potential for novel zoonosis of primate lentiviruses.
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, Shurl and Kay Curci Foundation, National Institutes of Health, National Institute on Aging, National Human Genome Research Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
Awards: Discovery and Characterization of Capsid-Targeting Lentiviral Restriction Factors, Cancer Center Support Grant, A compendium of complete primate reference genomes to facilitate conservation, genomics, and ecology, UCSF-Bay Area Center for AIDS Research, CHEETAH Center for the Structural Biology of HIV Infection, Restriction, and Viral Dynamics, Center for Alzheimer's and Related Dementias (CARD): Harmonized Data-Derived Resources for the Alzheimer's Disease and Related Dementias Community, The evolution and diversity of mutation, molecular fidelity, and genome structure
OpenAlex ID: W7212113376