Antibody Responses to HIV-1 gp120 Hypervariable Regions in Six Long-Term Non-Progressors

Rebecca Rivera,Xia Li,Francisco Diaz-Mitoma,Yasuhiro Yamamura,Eddy Rios-Olivares,Kyung Hee Kang,David E Anderson,José V Torres,Santiago Collado-Chastel,Murray B Gardner

doi:10.3844/ajidsp.2016.38.45

Abstract

Our long-term goal is to discover the combination of host parameters that help some HIV-infected individuals to resist progression to AIDS. In this study, we examined antibody responses using multiple samples obtained from a cohort of Long-Term Non-Progressors (LTNPs). Our hypothesis is that antibody responses to variable regions of the HIV-1 envelope glycoprotein are involved in reducing the viral load associated with LTNPs and that these specific immune responses influence susceptibility to disease progression. Multiple plasma samples were obtained from patients identified as LTNPs with the objective of characterizing humoral immune response directed to the five hypervariable regions of the envelope glycoprotein. Antibody binding was tested against peptides representing the five hypervariable regions of gp120, as well as against analog peptides representing different isolates of HIV-1 and against recombinant envelope glycoprotein. LTNPs have specific antibodies to the hypervariable regions of the envelope glycoprotein and develop different patterns of antibody recognition to variable epitopes of envelope glycoprotein. These antibodies can be detected using HIV peptides as capture antigens.

Highlights

The envelope glycoprotein (Env) of HIV-1 is formed by heterodimers in a trimeric configuration, consisting of three gp120 surface envelope glycoproteins noncovalently bound to three gp41 transmembrane glycoproteins (Helseth et al, 1991; Wyatt and Sodroski, 1998)
Hypervariable Epitope Constructs (HECs) was stronger than to the monovalent peptides that represent single strains of HIV-1. It is apparent from the present longitudinal study of a few Long-Term NonProgressors (LTNPs) patients that these individuals mount a humoral immune response that includes antibodies specific to the five variable epitopes studied
It was surprising to observe that antibodies from all the LTNPs examined reacted to each of the individual HIV HECs and that the overall antibody response to HIV used by HIV to infect target cells (Jensen and van't Wout, 2003) (Jensen et al, 2003)

Summary

Introduction

The envelope glycoprotein (Env) of HIV-1 is formed by heterodimers in a trimeric configuration, consisting of three gp120 surface envelope glycoproteins noncovalently bound to three gp transmembrane glycoproteins (Helseth et al, 1991; Wyatt and Sodroski, 1998). The gp120 surface envelope glycoprotein of HIV-1 mediates viral attachment to target cells and elicits antibodies that neutralize HIV infection (Pantophlet and Burton, 2006). The third hypervariable region (V3) is considered the major viral determinant of co-receptor specificity due to the fact that the co-receptor binding site resides primarily in the V3 region following conformational changes induced by binding to CD4. The V3 region contains antigenic epitopes that induce both cellular and humoral immune responses, including neutralizing antibodies (Fomsgaard et al, 1998; Cardozo et al, 2009; Swetnam et al, 2010). We assessed the immunogenicity of HIV HECs in rhesus macaques and rabbits (Carlos et al, 2000) and showed that HIV HECs are strong immunogens, eliciting both humoral and cellular immune responses. We wanted to determine to what extent LTNPs have antibodies that recognize the HIV gp120 hypervariable regions and if their antibody response would change during the time period examined

Material and Methods

Result

Findings

Discussion