Single amino acid change in Tat determines the different rates of replication of two sequential HIV-1 isolates.
Human immunodeficiency virus type 1 (HIV-1) isolates display differences in their patterns of replication in vitro. Previous studies with recombinant viruses generated between two sequential HIV-1 isolates that differ in replication rates have shown that the determinant for this biological property maps to a region of the viral genome that encompasses the tat gene. In the present study, we examined if there is a functional difference in the Tat protein of the two isolates. We observed that the level of transactivation induced by Tat of the fast replicating, highly cytopathic virus (HIV-1SF13mc) was three- to eightfold higher than the level seen by the Tat of the slow replicating virus (HIV-1SF2mc). Furthermore, a single amino acid mutation in the HIV-1SF13mc. Tat leads to reduced transactivation activity of the mutant protein and a delayed replication rate of the mutant virus. Thus, selection of a Tat variant with higher transactivation potential could be responsible for the increased virus production that is often associated with a pathogenic HIV strain.
LeGuern
M
M
Cancer Research Institute, School of Medicine, University of California, San Francisco 94143.
Shioda
T
T
Levy
J A
JA
Cheng-Mayer
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004279:DNA, Viral; D015696:Gene Products, tat / Q000235:genetics* / Q000378:metabolism; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D013601:T-Lymphocytes / Q000382:microbiology; D015533:Transcriptional Activation; D014162:Transfection; D014779:Virus Replication / Q000235:genetics; D054322:tat Gene Products, Human Immunodeficiency Virus
D004279:DNA, Viral; D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus