Development of a neutralizing antibody response during acute primary human immunodeficiency virus type 1 infection and the emergence of antigenic variants.
We monitored the primary humoral response to human immunodeficiency virus type 1 infection and showed that, in addition to antibodies to p24 and gp41, antigens which form the basis of most diagnostic assays, the response included a significant antibody response directed to the gp120 region of the infecting viral quasispecies. When tested in a recombinant virus neutralization assay, these antibodies were capable of inhibiting viral growth. We found the primary viral quasispecies to solely utilize the CCR-5 chemokine receptor; however, recombinant viruses differed in their cytopathology and in their sensitivity to beta-chemokine inhibition of viral growth. Sequence analysis of the gp120 open reading frames showed that amino acid changes in the C1 (D-->G at position 62) and C4 (V-->A at position 430) regions accounted for the phenotypic differences. These data demonstrate that early in infection, polymorphism exists in envelope glycoprotein coreceptor interactions and imply that therapeutic strategies targeted at this step in the viral life cycle may lead to rapid resistance.
Lewis
J
J
School of Animal and Microbial Sciences, University of Reading, Reading RG6 2AJ, United Kingdom.
Balfe
P
P
Arnold
C
C
Kaye
S
S
Tedder
R S
RS
McKeating
J A
JA
D000595:Amino Acid Sequence; D000940:Antigenic Variation; D002678:Chimera / Q000235:genetics; D003588:Cytopathogenic Effect, Viral / Q000235:genetics / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood*; D015488:HIV Antigens / Q000097:blood / Q000235:genetics*; D016655:HIV Core Protein p24 / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000097:blood / Q000235:genetics; D006679:HIV Seropositivity / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D016366:Open Reading Frames; D010641:Phenotype; D019713:Receptors, CCR5 / Q000502:physiology; D013997:Time Factors; D014766:Viremia / Q000276:immunology / Q000821:virology
D015483:HIV Antibodies; D015488:HIV Antigens; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5