Alteration of V3 loop context within the envelope of human immunodeficiency virus type 1 enhances neutralization.

Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.

Alteration of V3 loop context within the envelope of human immunodeficiency virus type 1 enhances neutralization.

J Virol. 1994 Jun;68(6):3459-66. Unique Identifier : AIDSLINE MED/94246688
Robert-Guroff M; Louie A; Myagkikh M; Michaels F; Kieny MP; White-Scharf ME; Potts B; Grogg D; Reitz MS Jr; Laboratory of Tumor Cell Biology, National Cancer Institute,; Bethesda, Maryland 20892.

Abstract: Neutralization of a chimeric human immunodeficiency virus (HIV) type 1, containing the V3 loop of the MN isolate substituted within the HXB2 envelope, was enhanced up to 20-fold compared with the HXB2 or MN parental isolates by human HIV-positive sera. MN V3 loop-specific monoclonal antibodies were better able to recognize the chimeric virus compared with MN, staining a greater percentage of infected cells and exhibiting slight increases in relative affinity with a concomitant increase in neutralization titer. Competition analysis revealed that enhanced neutralization by human HIV-positive sera of the chimera was attributable in some cases to better reactivity with the linear V3 loop epitope but in others to conformational loop epitopes or previously cryptic or poorly recognized epitopes outside the loop region. Mice primed with a vaccinia virus-chimeric envelope recombinant and boosted with gp160 developed a spectrum of antibodies different from that of mice similarly immunized with HXB2 or MN recombinants or that of naturally infected humans. The chimeric envelope elicited antibodies with enhanced binding to the native MN V3 loop; however, the sites seen by the BALB/c mice were not neutralizing epitopes. Nevertheless, similar to the observations made with use of human sera, the chimeric virus was more readily neutralized by all of the immune mouse sera, an effect apparently mediated by non-V3 loop epitopes. These studies illustrate that not only the V3 loop sequence and conformation but also its context within the viral envelope influence neutralization.

Keywords: Amino Acid Sequence Animal Antibodies, Monoclonal Antibody Specificity AIDS Vaccines/IMMUNOLOGY Base Sequence Binding, Competitive Cell Line Chimera/GENETICS/IMMUNOLOGY Comparative Study DNA, Viral/GENETICS Epitopes Human HIV Antibodies HIV Envelope Protein gp120/GENETICS/*IMMUNOLOGY HIV-1/GENETICS/*IMMUNOLOGY Mice Mice, Inbred BALB C Molecular Sequence Data Neutralization Tests Peptide Fragments/GENETICS/*IMMUNOLOGY JOURNAL ARTICLE
940830
M9480016

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