HIV-1 gp120 N-linked glycosylation differs between plasma and leukocyte compartments

Yung Shwen Ho,Anne Mieke Vandamme,Dominic E Dwyer,Ana B Abecasis,Koen Deforche,Nitin K Saksena,Kristof Theys,Michael Charleston

doi:10.1186/1743-422x-5-14

Abstract

BackgroundN-linked glycosylation is a major mechanism for minimizing virus neutralizing antibody response and is present on the Human Immunodeficiency Virus (HIV) envelope glycoprotein. Although it is known that glycosylation changes can dramatically influence virus recognition by the host antibody, the actual contribution of compartmental differences in N-linked glycosylation patterns remains unclear.Methodology and Principal FindingsWe amplified the env gp120 C2-V5 region and analyzed 305 clones derived from plasma and other compartments from 15 HIV-1 patients. Bioinformatics and Bayesian network analyses were used to examine N-linked glycosylation differences between compartments. We found evidence for cellspecific single amino acid changes particular to monocytes, and significant variation was found in the total number of N-linked glycosylation sites between patients. Further, significant differences in the number of glycosylation sites were observed between plasma and cellular compartments. Bayesian network analyses showed an interdependency between N-linked glycosylation sites found in our study, which may have immense functional relevance.ConclusionOur analyses have identified single cell/compartment-specific amino acid changes and differences in N-linked glycosylation patterns between plasma and diverse blood leukocytes. Bayesian network analyses showed associations inferring alternative glycosylation pathways. We believe that these studies will provide crucial insights into the host immune response and its ability in controlling HIV replication in vivo. These findings could also have relevance in shielding and evasion of HIV-1 from neutralizing antibodies.

Highlights

The Human Immunodeficiency Virus (HIV)-1 envelope gp120 region plays a crucial role in the entry of HIV-1 into target cells through the fusion of viral envelope with the target cell membrane
Phylogenetic analysis on the 305 HIV-1 env gp120 C2-V5 region sequences from plasma, peripheral blood mononuclear cells, CD4+ T cells, CD8+ T cells and monocytes
Even though we found evidence for compartmentalization of HIV-1 across plasma and diverse blood leukocyte populations in vivo, it is important to note that the N-linked glycosylation (NLG) observed in our sequences are distinctly patient-specific (p ≤ 2.2 × 10-16)

Summary

Introduction

The HIV-1 envelope (env) gp120 region plays a crucial role in the entry of HIV-1 into target cells through the fusion of viral envelope with the target cell membrane. Variable regions (V1-V5) in env are spaced between the conserved regions (C1-C5) Both N-linked and O-linked glycans are present on the HIV envelope glycoprotein. The N-linked glycosylation (NLG) of viral envelope proteins, through the formation of a "glycan shield", is one of the major mechanisms for blocking or minimizing virus neutralizing antibody response [4]. Any alteration or positional shift of a glycosylation site (commonly seen in HIV and SIV glycoproteins) can have dramatic consequences for the virus and its recognition by the antibody. N-linked glycosylation is a major mechanism for minimizing virus neutralizing antibody response and is present on the Human Immunodeficiency Virus (HIV) envelope glycoprotein. It is known that glycosylation changes can dramatically influence virus recognition by the host antibody, the actual contribution of compartmental differences in N-linked glycosylation patterns remains unclear

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Conclusion