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HIV-1 glycan density drives the persistence of the mannose patch within an infected individual.

HIV-1 glycan density drives the persistence of the mannose patch within an infected individual.
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Coss KP, Vasiljevic S, Pritchard LK, Krumm SA, Glaze M, Madzorera S, Moore PL, Crispin M, Doores KJ,


Coss KP, Vasiljevic S, Pritchard LK, Krumm SA, Glaze M, Madzorera S, Moore PL, Crispin M, Doores KJ, (click to view)

Coss KP, Vasiljevic S, Pritchard LK, Krumm SA, Glaze M, Madzorera S, Moore PL, Crispin M, Doores KJ,

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Journal of virology 2016 Oct 5() pii

Abstract

The HIV envelope (Env) is extensively modified with host-derived N-linked glycans. The high density of glycosylation on the viral spike limits enzymatic processing resulting in numerous under-processed oligomannose-type glycans. This extensive glycosylation not only shields conserved regions of the protein from the immune system but also act as targets for HIV broadly neutralizing antibodies (bnAbs). In response to the host immune system, the HIV glycan shield is constantly evolving through mutations affecting both the positions and frequencies of potential N-linked glycans (PNGSs). Here, using longitudinal Env sequences from a clade C infected individual (CAP256), we measure the impact of the shifting glycan shield during HIV infection on the abundance of oligomannose-type glycans. By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS frequency and positioning, we show that the intrinsic mannose-patch persists throughout the course of HIV infection and correlates with the number of PNGSs. This effect of glycan density on processing state was also supported by the analysis of a cross-clade panel of recombinant gp120 glycoproteins. Together, these observations underscore the importance of glycan clustering for the generation of carbohydrate epitopes for HIV bnAbs. The persistence of the intrinsic mannose patch over the course of HIV infection further highlights this epitope as an important target for HIV vaccine strategies.

IMPORTANCE
Development of an HIV vaccine is critical for control of the HIV pandemic, and elicitation of broadly neutralizing antibodies (bnAbs), is likely to be a key component of a successful vaccine response. The HIV Envelope glycoprotein (Env) is covered in an array of host-derived N-linked glycans often referred to as the glycan shield. This glycan shield is a target for many of the recently isolated HIV bnAbs and is therefore under constant pressure from the host immune system leading to changes in both glycan site frequency and location. This study aimed to determine whether these genetic changes impacted the eventual processing of glycans on the HIV Env, and the viruses susceptibility to neutralization. We show that despite this variation in glycan site positioning and frequency over the course of HIV infection, the mannose patch is a conserved feature throughout, making it a stable target for HIV vaccine design.

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