Of the two lineages of lentivirus that endemically infect chimpanzees, only one has served as a source of infections in hu-mans. 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 replica-tion. 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.
Young, M. J., Cotera, F., Gill, C. C. C., Lewis, J. A., Whitby, F. G., Abdellatif, A., Rocha, J. L., Singer, M., Nalls, M. A., Faghri, F., Sudmant, P. H., Pornillos, O., Ohainle, M.
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