Replication-defective HIV isolated from seronegative individuals at high risk for HIV infection.
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.
Hamano
Takaichi
T
High-tech Research Centre, Chiba Institute of Technology, 2-17-1 Tudanuma, Narashino-shi, Chiba, Japan.
Matsuo
Kazuhiro
K
Hibi
Yurina
Y
Takahashi
Naoko
N
Mabuchi
Yoshio
Y
Soji
Tsuyoshi
T
Irie
Shinji
S
Yanai
Hideki
H
Hara
Takashi
T
Yamazaki
Shudo
S
Yamamoto
Naoki
N
Takaku
Hiroshi
H
Okamoto
Takashi
T
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
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