title: 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.
abstract: 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.
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
authors.forename: R L
authors.initials: RL
authors.lastname: Willey
authors.forename: T S
authors.initials: TS
authors.lastname: Theodore
authors.forename: M A
authors.initials: MA
authors.lastname: Martin
mesh_terms: 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*
chemical_list: 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