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Mutational pressure makes HIV1 gp120 linear B-cell epitopes shorter and may lead to their disappearance.

Abstract：

:We showed that nucleotide sequences coding for linear B-cell epitopes of human immunodeficiency virus type 1 (HIV1) gp120 protein are enriched with codons containing cytosine and guanine in their first and second codon positions. Guanine and cytosine are the most mutable nucleotides in HIV1 genes (due to APOBEC3 and APOBEC1 editing of viral DNA and RNA, respectively, as well as due to reverse transcriptase preference to incorporate 8-oxo-G against C). We introduced all the possible G to A, C to U, C to A and G to U single nonsynonymous nucleotide mutations in gp120 coding region from the HIV1 reference strain. The BepiPred algorithm (www.cbs.dtu.dk/services/BepiPred) was used for the linear B-cell epitopes predictions. Results of this "in-silico directed mutagenesis" showed that: (i) single nonsynonymous G to A transitions will cause partial or complete destruction of linear epitopes in 18% of 229 possible cases; (ii) single nonsynonymous C to U transitions will cause partial or complete destruction of linear epitopes in 58% of 142 possible cases; (iii) single nonsynonymous C to A transversions will cause partial or complete destruction of linear epitopes in 28% of 184 possible cases; (iv) single nonsynonymous G to U transversions will cause partial or complete destruction of linear epitopes in 37% of 240 possible cases. Moreover, single transition of C to U direction leading to amino acid replacement inside an epitope will cause partial or complete destruction of this epitope at a probability of 98%.

journal_name

Mol Immunol

journal_title

Molecular immunology

authors

Khrustalev VV

doi

10.1016/j.molimm.2010.01.006

subject

Has Abstract

pub_date

2010-04-01 00:00:00

pages

1635-9

issue

7-8

eissn

0161-5890

issn

1872-9142

pii

S0161-5890(10)00007-6

journal_volume

47

pub_type

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