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

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%.