BACK TO CONTENTS   |    PDF   |    PREVIOUS   |    NEXT

Title

Neutralization function affected by single amino acid replacement in the HIV-1 antibody targets

 

Authors

Johnson Christdas1, Prabu Manoharan2 & Shakila Harshavardhan1*

 

 

Affiliation

1Department of Molecular Microbiology, School of Biotechnology, Madurai Kamaraj University, Madurai, Tamil Nadu, India, 625021; 2Centre of Excellence in Bioinformatics, Madurai Kamaraj University, Madurai, Tamil Nadu, India, 625021

 

 

Email

mohanshakila@yahoo.com; *Corresponding author

 

Article Type

Hypothesis

 

Date

Received December 01, 2014; Accepted January 08, 2015; Published February 28, 2015

 

Abstract

The viral envelope glycoproteins are essential for entry into their host cells and studied extensively for designing vaccines. We hypothesize that the glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical residues offers viral escape from the specific immune surveillant neutralizing antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane Proximal External Region (MPER). The glycosylation occurring on the 50th residue (Asparagine) contained in the target (NWFNIT) can mask itself to be inaccessible for these neutralizing antibodies. The glycosylation rate of the epitopes which are shared by the Z13, 4E10 and 10E8 neutralizing antibodies of HIV-1 were predicited in silico. We analyzed the reliable frequency of glycosylation on the HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41 trimer (PDBID: 2M7W and 2LP7). It is evident that the glycosylation by a mannose that masks these targets is possible only when the 50th amino-acid is N (Asparagine, Asn) which is not possible when N is mutated to D (Aspartatic acid, Asp). The additive advantage for the retrovirus is its error-prone reverse transcriptase which can choose to copy these survivable mutants with Asn N-50 that can be glycosylated as explained by the Copy-choice model. So the glycan shields varying in their intensity and patterns have to be essentially studied to understand the viral escape strategies that will give a way forward towards a successful vaccine that can elicit a neutralizing antibody response to confer protection. 

 

Keywords

N- linked glycosylation; HIV gp41; Immune escape; Neutralizing antibodies; Immunogens.

 

Citation

Christdas et al.   Bioinformation 11(2): 057-062 (2015)
 

Edited by

P Kangueane

 

ISSN

0973-2063

 

Publisher

Biomedical Informatics

 

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.