Host range, replicative, and cytopathic properties of human immunodeficiency virus type 1 are determined by very few amino acid changes in tat and gp120.
Human immunodeficiency virus type 1 (HIV-1) isolates display differences in a variety of in vitro biological properties, including the ability to infect different cell types, the kinetics of replication, and cytopathicity in the infected cells. Studies with isolates obtained from the same individual over time have shown that these in vitro properties of the viral isolates correlate with pathogenicity in the host. The later isolates, recovered when disease has developed, display a wider cellular host range, replicate rapidly and to high titers in the infected cells, and induce syncytia in these cells. In the present studies, the genomic determinants of these biological properties were defined with recombinant viruses generated between two HIV-1 isolates recovered sequentially from the same individual. The results show that the rate of HIV-1 replication in the HUT 78 T-cell line is controlled by the first coding exon of tat. Infection of T-cell and monocytic cell lines is determined by two specific regions in the envelope gp120, one of which also confers the ability of an isolate to induce syncytia. Amino acid sequence comparison of the regions identified revealed minor differences between the two viral isolates: 2 amino acids in the tat gene product and 10 and 12 amino acids in the two regions of envelope gp120. These data suggest that small changes in the tat and env proteins can have dramatic effects on the pathogenic potential of HIV-1.
Cheng-Mayer
C
C
Cancer Research Institute, University of California School of Medicine, San Francisco 94143-0128.
Shioda
T
T
Levy
J A
JA
D000163:Acquired Immunodeficiency Syndrome / Q000382:microbiology; D000595:Amino Acid Sequence; D001358:Avian Sarcoma Viruses / Q000235:genetics; D002460:Cell Line; D003001:Cloning, Molecular; D004274:DNA, Recombinant / Q000302:isolation & purification; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D015696:Gene Products, tat / Q000235:genetics*; D015756:Genes, tat; D015726:Giant Cells / Q000166:cytology; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009000:Monocytes; D011995:Recombination, Genetic; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes; D016662:Virus Integration; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus
D004274:DNA, Recombinant; D004279:DNA, Viral; D015696:Gene Products, tat; D015699:HIV Envelope Protein gp120; D054322:tat Gene Products, Human Immunodeficiency Virus