title: Gag-CA Q110D mutation elicits TRIM5-independent enhancement of HIV-1mt replication in macaque cells.
abstract: HIV-1 is strictly adapted to humans, and cause disease-inducing persistent infection only in humans. We have generated a series of macaque-tropic HIV-1 (HIV-1mt) to establish non-human primate models for basic and clinical studies. HIV-1mt clones available to date grow poorly in macaque cells relative to SIVmac239. In this study, viral adaptive mutation in macaque cells, G114E in capsid (CA) helix 6 of HIV-1mt, that enhances viral replication was identified. Computer-assisted structural analysis predicted that another Q110D mutation in CA helix 6 would also increase viral growth potential. A new proviral construct MN4Rh-3 carrying CA-Q110D exhibited exquisitely enhanced growth property specifically in macaque cells. Susceptibility of MN4Rh-3 to macaque TRIM5α/TRIMCyp proteins was examined by their expression systems. HIV-1mt clones so far constructed already completely evaded TRIMCyp restriction, and further enhancement of TRIMCyp resistance by Q110D was not observed. In addition, Q110D did not contribute to evasion from TRIM5α restriction. However, the single-cycle infectivity of MN4Rh-3 in macaque cells was enhanced relative to the other HIV-1mt clones. Our results here indicate that CA-Q110D accelerates viral growth in macaque cells irrelevant to TRIM5 proteins restriction.
authors.affiliation: Department of Microbiology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto, Tokushima 770-8503, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Nomaguchi
authors.forename: Masaru
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Ken
authors.initials: K
authors.lastname: Kono
authors.forename: Emi E
authors.initials: EE
authors.lastname: Nakayama
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Shioda
authors.forename: Akatsuki
authors.initials: A
authors.lastname: Saito
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Akari
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yasutomi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matano
authors.forename: Hironori
authors.initials: H
authors.lastname: Sato
authors.forename: Akio
authors.initials: A
authors.lastname: Adachi
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002415:Cats; D002460:Cell Line; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D008251:Macaca; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D014779:Virus Replication / Q000235:genetics*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000378:metabolism
chemical_list: D036022:Capsid Proteins; D002352:Carrier Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus