title: Replication-defective HIV isolated from seronegative individuals at high risk for HIV infection.
abstract: We have identified a mutant human immunodeficiency virus type 1 (HIV-1) CRF01_AE that contains a single nucleotide mutation in gag gene from 4 HIV-1 seronegative drug users in Thailand. We found A to G mutation at the nucleotide position 75 of gag p17 gene (A75G) not changing the amino acid sequence. The mutant HIV-1 molecular clones were examined for their replication capability. Although the mutation dramatically reduced the level of virion production, it did not affect the amounts of viral protein synthesis within the transfected cells. In addition, this mutation did not affect the levels of Gag polyproteins. Furthermore, electron microscopic examinations have revealed a dramatic reduction of the virion production and perturbation of viral morphogenesis at the cytoplasmic membrane. These results indicate that the A75G mutation is attributable to the long-term sero-negativity of individuals at high risk of HIV-1 infection and suggest a novel mechanism that regulates HIV production.
authors.affiliation: High-tech Research Centre, Chiba Institute of Technology, 2-17-1 Tudanuma, Narashino-shi, Chiba, Japan.
authors.forename: Takaichi
authors.initials: T
authors.lastname: Hamano
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Yurina
authors.initials: Y
authors.lastname: Hibi
authors.forename: Naoko
authors.initials: N
authors.lastname: Takahashi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Mabuchi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Soji
authors.forename: Shinji
authors.initials: S
authors.lastname: Irie
authors.forename: Hideki
authors.initials: H
authors.lastname: Yanai
authors.forename: Takashi
authors.initials: T
authors.lastname: Hara
authors.forename: Shudo
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takaku
authors.forename: Takashi
authors.initials: T
authors.lastname: Okamoto
mesh_terms: D015683:Gene Products, gag / Q000145:classification / Q000235:genetics*; D015488:HIV Antigens / Q000145:classification / Q000235:genetics*; D015658:HIV Infections / Q000453:epidemiology; D018023:HIV Seronegativity; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D010802:Phylogeny; D017354:Point Mutation; D019966:Substance-Related Disorders / Q000150:complications; D014764:Viral Proteins / Q000145:classification / Q000235:genetics*; D014771:Virion / Q000648:ultrastructure; D014779:Virus Replication / Q000235:genetics*; D054301:gag Gene Products, Human Immunodeficiency Virus
chemical_list: D015683:Gene Products, gag; D015488:HIV Antigens; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1