V4 region of the HIV-1 envelope gene mediates immune escape and may not promote the development of broadly neutralizing antibodies. Issue 50 (29th November 2018)

• Record Type: Journal Article
• Authors: Ji, Yangtao; Han, Xiaoxu; Tian, Wen; Gao, Yang; Jin, Su; Zhang, Linqi; Shang, Hong
• Is Part Of: Vaccine. Volume 36:Issue 50(2018)
• Page Start: 7700
• Page End: 7707
• Publication Date: 2018-11-29
• Subjects: HIV-1 -- CRF01_AE -- V4 region -- Broadly neutralizing antibodies -- Vaccine; bnAbs broadly neutralizing antibodies -- ss-Abs strain-specific antibodies -- T/F virus transmit/founder virus -- nAbs neutralizing antibodies -- CD4bs CD4 binding site -- MSM men who have sex with men -- VL viral load -- ID50 half-maximal inhibitory dilutions -- OD optical densities -- TCID50 50% tissue culture infective dose -- ELISA Enzyme-linked immunosorbent assay; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2018.10.084
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: The mutations appeared firstly in V4 region and mediated virus escape. Strain-specific antibodies appeared early, driving the evolution of virus. Coevolution of V4 and ss-Abs promoted nAbs development, failed to produce bnAbs. The V4 region of HIV-1 envelope might not be a good target for an HIV-1 vaccine. Abstract: To date, inducing the production of broadly neutralizing antibodies (bnAbs) against HIV-1 in humans has been unsuccessful. Several studies have explored the coevolution of HIV-1 and neutralizing antibodies (nAbs), but little is known about what affects the lack of bnAbs after long-term infection. A better understanding of the coevolution of the virus and nAbs in cases involving no bnAb production will help in the design of an effective HIV-1 vaccine. An individual with acute CRF01_AE HIV-1 infection who lacked bnAbs at just over 2 years post-infection (p.i.) was identified from a cohort of HIV negative men who have sex with men. The coevolution of the viral envelope gene and nAbs was studied over 741 days p.i. Strain-specific antibodies (ss-Abs) to the transmitted/founder (T/F) virus developed within 54 days p.i., but plasma collected at subsequent time points could not neutralize synchronous viruses until 557 days p.i., when the plasma acquired low-level synchronous but not heterologous neutralizing activity. The V4 region of envelope gene mutated firstly and continually evolve up to 2 years p.i. Multiple variations in the V4 region, including substitutions, deletions and glycosylation mutations, were driven by ss-Abs and mediated immune escape partially by impacting the binding of nAbs to the virus. The remarkable variations in the V4 region mediated immune escape from ss-Abs and contributed to the affinity maturation of ss-Abs against the T/F virus but may not promote the development of bnAbs. Thus, the V4 region might not be a good target for an HIV-1 vaccine.