title: Heterogeneity of envelope molecules shown by different sensitivities to anti-V3 neutralizing antibody and CXCR4 antagonist regulates the formation of multiple-site binding of HIV-1.
abstract: Increased temperature enhances the infectivity of human immunodeficiency virus type 1 (HIV-1), and this enhancement is inhibited by anti-CXCR4 peptide T140, implying that multiple-site binding is required to proceed to infection. Here, we tested whether the augmented infectivity induced by increased temperature could account for the heterogeneity of envelope molecules in the effectiveness of anti-V3 neutralization and anti-CXCR4 blocking. Pseudoviruses with the X4 envelope which were infectious at room temperature (RT) were more resistant to both anti-V3 neutralizing antibody 0.5beta and T140 than viruses infectious at 37 C and 40 C. Viruses infectious to cells treated with T140 were also resistant to 0.5beta. Based on the hypothesis that the HIV-1 viruses were carrying heterogeneity of functional and nonfunctional gp120 and required the formation of sufficient multiple-site binding of functional gp120 with receptors to proceed to infection, viruses with many functional gp120 which were infectious at RT and infectious to cells with reduced numbers of CXCR4 by T140 treatment were resistant to 0.5beta. Although viruses with many functional gp120 are a minority (less than 5%) of the infectious HIV-1 fraction, they are regarded as able to escape from neutralizing antibodies and coreceptor antagonists.
authors.affiliation: Department of Medical Virology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. biodef@gpo.kumamoto-u.ac.jp
authors.forename: Shinji
authors.initials: S
authors.lastname: Harada
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yusa
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Maeda
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D014644:Genetic Variation; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D019718:Receptors, CXCR4 / Q000276:immunology / Q000378:metabolism; D015728:Receptors, HIV / Q000378:metabolism*
chemical_list: D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D010455:Peptides; D019718:Receptors, CXCR4; D015728:Receptors, HIV