COMPARATIVE ANALYSIS OF AFSU HIV-1 VARIANTS CIRCULATING IN IDUs AND HETEROSEXUAL POPULATIONS

Abstract



INTRODUCTION The widespread HIV epidemic in the Perm region, as well as in the whole country, began with the entry of HIV-1 subtype A1 (AFSU) into injecting drug users (IDUs) population in the mid-90-s. The rapid spread of the virus in the population of IDUs and their sexual partners subsequently led to the AFSu variant output outside of the risk group and spread in the population of those infected through heterosexual contact ("heterosexual") and not associated with the IDUs. MATERIALS AND METHODS Blood samples from 142 naive HIV-infected patients from Perm infected between 1996 and 2011 were collected, of which 91 belonged to the IDUs risk group and 51 were heterosexuals. The fragments of pol gene (PR-RT, 954 bp) and env (C2-V4, 498 bp) was obtained by the "nested" PCR, followed by sequencing. Phylogenetic analysis was carried out using BEAST v. 1.8.2 software package (http://beast.bio.ed.ac.uk). Reconstruction of the most recent common ancestor (tMRCA) and divergence estimation were performed using MEGA v. 6.0 program (http://megasoftware.net/). The search for the codons positive with regard to selection was carried out using DataMonkey (http://datamonkey.org); glycosylation sites were searched using the programs N-GlycoSite (http://hiv.lanl.gov) and NetPhos 2.0 (http://cbs.dtu.dk). ■ A1 Africa ■ A1 Perm (Afsu) ■ A1 Africa ■ A1 Odessa (Afsu) ■ A1 Perm (Afsu) Fig. 1. Bayesian MCC tree for 215 HIV-1 subtype A1 polRj.RR (a) and envC2-C4 (b) sequences. The Bayesian skyline plot below shows the changes in Afsu variant effective population size on the territory of Perm region. RESULTS The analysis of poIpr.rt and envc2-v4 genome regions in 142 HIV-1 samples from Perm showed that in this part of Russia the AFSu variant appeared in 1992-1994 (data of TMRCA - 1992 and 1994, for pol and env gene, respectively) (Fig. 2a, b). The degree of divergence between the AFSu variants and TMRCA increased with time (r = 0,71; p <0,01) during 1996-2011 in pol and env genes from 1.75% to 3.02% and from 2.98% to 6.29%, respectively. The mean evolution rate in polpR-RT and envc2-c4 genome regions of the AFSu variants in heterosexual population (n = 51) was higher than that for IDUs (n = 57) by 1.5 and 2.1 times, respectively (Fig. 2a). The 106 МЕДИЦИНСКИЙ АКАДЕМИЧЕСКИЙ ЖУРНАЛ, 2016 г., ТОМ 16, № 3 □ IDUs Heterosexual 8.00-і 12.00-1 g 10.00£ » 1 g B.00-1 -□ = ■g S Е.00Н з « O -° Ф ^ 4*004 p <0,01 pol PR - RT env C2-C4 Genome region of HIV-1 p 0.01 p < 0 01 0.00 pol PR - RT env C2-C4 b Genome region of HIV-1 Fig. 2. The evolutionary rate (a) and nucleotide diversity (b) for the poIpr-rt and envc2-c4 regions of the Afsu HIV-1 variant for IDUs and heterosexual populations. a a Arneno acid position {gp120 HXB2 ) b Amino acid position ( gp120 HXB2 ) Fig. 3. Positions under positive selection (a) and glycosylation sites (b) in the HIV-1 C2-C4 region gpl20 among Afsu variants spreading in IDUs and heterosexual populations. average nucleotide diversity of these genome regions was also higher for the variants circulating among heterosexuals (Fig. 2b). Positive selection in the envc2-c4 genome region of the Afsu HIV-1 was detected in 21 positions, 14 of which differed depending on the risk group (Fig. 3a). The profile and frequency of glycosylation of 17 amino acid sites in envc2-c4 region of Afsu HIV-1 showed no differences between the risk groups (Fig. 3b). CONCLUSIONS The evolution of Afsu HIV-1 variants dominating in Perm region shows the strong temporal structure characterized by pol and env genes diversification over time. The uneven rate of evolution and the differences in the profile of sites subjected to selection among viruses that spread in IDUs and heterosexuals populations can be caused by different rates of HIV-1 spread in these risk and, consequently, different levels of immune system selective pressure upon the virus population.

A Lebedev

Gamaleya Federal Research Center of Epidemiology and Microbiology

Moscow, Russia

E Kazennova

Gamaleya Federal Research Center of Epidemiology and Microbiology

Moscow, Russia

M Bobkova

Gamaleya Federal Research Center of Epidemiology and Microbiology

Moscow, Russia

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Copyright (c) 2016 Lebedev A., Kazennova E., Bobkova M.

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