title: Single-amino acid mutation 66SR in Gag-matrix enhances viral single-cycle infectivity of R5-tropic HIV-1rmt.
abstract: We recently constructed two rhesus macaque-tropic human immunodeficiency virus type 1 (HIV-1rmt) clones with CXCR4 or CCR5 tropism, but a CCR5-tropic HIV-1rmt clone grew more poorly than a CXCR4-topic clone. It has been demonstrated that interaction between viral Gag-matrix (MA) and Env-gp41 cytoplasmic tail is important for virion-incorporation of Env. Concordantly, Gag-MA mutations (62QR and 66SR) that rescue defects in virion-incorporation of Env/viral replication were reported. In this study, we analyzed effects of these Gag-MA mutations on R5-tropic HIV-1rmt replication potentials. While introduction of 62QR into three HIV-1rmt clones tested reduced their multi-cycle replication ability in rhesus lymphocytes or abolish single-cycle infectivity for luciferase reporter cells, three R5-tropic HIV-1rmt clones carrying 66SR exhibited similar growth kinetics to those of their parental clones. One such clone, 66SR+5gtu, appeared to induce stronger cytopathic effects than parental clone 5gtu. We therefore investigated effects of 66SR mutation on viral replication in more detail. Single-cycle infectivity of 66SR+5gtu was enhanced relative to that of 5gtu, but 66SR+5gtu virion production was significantly decreased compared to the 5gtu level. Gag-MA 66SR mutation may be useful to improve growth potentials of the R5-tropic HIV-1rmt clones.
authors.affiliation: Department of Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Naoya
authors.initials: N
authors.lastname: Doi
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Sakai
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Akio
authors.initials: A
authors.lastname: Adachi
authors.forename: Masako
authors.initials: M
authors.lastname: Nomaguchi
mesh_terms: D000818:Animals; D015683:Gene Products, gag / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity*; D008253:Macaca mulatta / Q000235:genetics*; D009154:Mutation; D014763:Viral Matrix Proteins / Q000235:genetics*; D056189:Viral Tropism; D019065:Virus Assembly; D014779:Virus Replication
chemical_list: D015683:Gene Products, gag; D014763:Viral Matrix Proteins