Chimeric viruses expressing primary envelope glycoproteins of human immunodeficiency virus type I show increased sensitivity to neutralization by human sera.
We constructed a number of HXB2 viruses chimeric for the gp 120 glycoprotein derived from a number of viable molecular clones obtained from a primary isolate. Comparative biological characterization of the parental primary viruses with the gp 120.HXB2 chimeras demonstrated identical patterns of cell tropism and cytopathicity. Furthermore, both parental and chimeric viruses were insensitive to neutralization by sCD4 and a panel of conformation-dependent monoclonal antibodies, demonstrating that transfer of the gp 120 protein alone was sufficient to confer a "neutralization-resistant" phenotype to the T-cell-adapted clone HXB2. We assessed the contribution of gp 120 epitopes to the neutralizing immune response by comparing the sensitivity of these viruses to neutralization by a panel of sera from HIV-infected individuals. Seven of eleven sera tested were able to neutralize HXB2 and two or more of the chimeric viruses; in contrast, only one serum neutralized more than one of the parental primary virus clones. The association of gp 120-gp41 envelope at the surface of infected PBMC cultures was measured in the presence or absence of soluble CD4. No differences in CD4-induced gp 120 dissociation were seen between the chimeric and parental virus-infected cultures. Since gp 120 conformation appeared the same between primary and chimeric viruses, we suggest that the ability of human sera to neutralize the chimeric viruses may be mediated by epitopes within gp41.
McKeating
J A
JA
University of Reading, School of Animal & Microbial Sciences, Whiteknights, United Kingdom.
Zhang
Y J
YJ
Arnold
C
C
Frederiksson
R
R
Fenyö
E M
EM
Balfe
P
P
D000595:Amino Acid Sequence; D010582:Bacteriophage lambda; D001483:Base Sequence; D015704:CD4 Antigens / Q000276:immunology; D002478:Cells, Cultured; D004279:DNA, Viral; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D016865:Reassortant Viruses / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D014407:Tumor Cells, Cultured
D015704:CD4 Antigens; D004279:DNA, Viral; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D011994:Recombinant Proteins; C076613:recombinant soluble CD4