Comparison of HIV epitopes availability between acute and chronic infection

G. DAMILANO; G. TURK; O. SUED; E. SOCIAS; M.J. RUIZ; F. GUZMAN; H. SALOMON; D. DILERNIA

Durban

Congreso; 21st International AIDS Conference (AIDS 2016); 2016

International AIDS Society

Background: Recent studies indicate that there is selection bias for transmission of viral polymorphisms associated with higher viral fitness. Furthermore, after transmission and before a specific immune response is mounted in the recipient, the virus undergoes a number of reversions which allow an increase in their replicative capacity. These aspects, and others, affect the viral population characteristic of early acute infection. Methods: 70single Gag-gene amplifications were obtained by limiting-dilution RT-PCR from plasma samples of 5 ARV-naïve patients with early acute infection (< 60days, 29 days average) and 5 ARV-naive patients with a year of infection (7amplicons per patient). Sanger sequencing and NGS SMRT technology (Pacific Biosciences) were implemented to sequence the amplicons. HLA-I typing was performed by SSOP-PCR method. The chromatograms were analyzed with Sequencher 4.10. Epitopes prediction was performed with NetMHC CBS prediction server for the 19 HLA-A and -B alleles most prevalent in our population with peptide lengths from 8 to 14 Aa. Citotoxic response prediction was performed by using the IEDB Analysis Resource. Results: After implementing epitope prediction analysis, we identified a total number of 110 viral epitopes present in two or more acute or chronic patients. 63.6% (n=70) of them were present only in acute infection (prevalent acute epitopes) while 36.4% (n=40) were present only in chronic infection (prevalent chronic epítopes). Within p24, the difference was even more dramatic with 85.7% (18/21) being acute epitopes. This is consistent with progressive viral adaptation to immune response in time and further supported by the fact that citotoxic response prediction shows that acute epítopes are more likely to generate immune response than chronic epítopes. Interestingly, only 15.2% of acute epítopes match the population-level consensus sequence of the virus. Deep NGS indicates that there is not significant variability in epitopes sequences. Conclusions: Our results indicate that certain non-consensus viral residues might be transmitted more frequently than consensus-residues when located in immulogicaly relevant positions (epítopes).This observation might be relevant to the rationale behind development of an effective vaccine.