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



Johnson Christdas1, Prabu Manoharan2 & Shakila Harshavardhan1*




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; *Corresponding author


Article Type




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



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. 



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



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

Edited by

P Kangueane






Biomedical Informatics



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