Amino acid substitutions in the human immunodeficiency virus type 1 gp120 V3 loop that change viral tropism also alter physical and functional properties of the virion envelope.
The third variable (V3) region within the gp120 envelope glycoprotein of the human immunodeficiency virus type 1 (HIV-1) has been reported to be an important determinant of viral tropism. In this study a series of isogenic recombinant HIV-1 viruses, containing V3 regions from fresh isolates, were examined to ascertain if a relationship exists between viral tropism and specific properties of the virion-associated envelope. All of the viruses were able to infect CD4+ primary lymphocytes, although with different infection kinetics. Several recombinants, however, were unable to infect a continuous CD4+ T-cell line permissive for the parental virus and exhibited a marked decrease in the kinetics of virion-associated gp120 binding to a soluble form of CD4. A known macrophage-tropic HIV-1 isolate, also unable to infect the T-cell line, bound CD4 with similarly slow reaction kinetics. Although the inability to infect T-cell lines is a commonly observed property of macrophage-tropic isolates of HIV-1, the loss of T-cell line tropism by the V3 recombinants was not accompanied by a substantial infectivity for monocyte-derived macrophages, as monitored by reverse transcriptase production. Additional analyses of the recombinant virion gp120s indicated that most of the V3 substitutions increased the inherent stability of the virion gp120-gp41 envelope complex. These results indicate that V3-induced alterations in viral tropism are associated with changes in physical and functional properties of the virion envelope.
Willey
R L
RL
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Theodore
T S
TS
Martin
M A
MA
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000235:genetics / Q000502:physiology*; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000502:physiology*; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D012194:RNA-Directed DNA Polymerase / Q000096:biosynthesis; D011995:Recombination, Genetic; D014771:Virion / Q000502:physiology*
D000596:Amino Acids; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase