Abstract
A number of HIV-1 subtypes are identified in Pakistan by characterization of partial viral gene sequences. Little is known whether new recombinants are generated and how they disseminate since whole genome sequences for these viruses have not been characterized. Near full-length genome (NFLG) sequences were obtained by amplifying two overlapping half genomes or next generation sequencing from 34 HIV-1-infected individuals in Pakistan. Phylogenetic tree analysis showed that the newly characterized sequences were 16 subtype As, one subtype C, and 17 A/G recombinants. Further analysis showed that all 16 subtype A1 sequences (47%), together with the vast majority of sequences from Pakistan from other studies, formed a tight subcluster (A1a) within the subtype A1 clade, suggesting that they were derived from a single introduction. More in-depth analysis of 17 A/G NFLG sequences showed that five shared similar recombination breakpoints as in CRF02 (15%) but were phylogenetically distinct from the prototype CRF02 by forming a tight subcluster (CRF02a) while 12 (38%) were new recombinants between CRF02a and A1a or a divergent A1b viruses. Unique recombination patterns among the majority of the newly characterized recombinants indicated ongoing recombination. Interestingly, recombination breakpoints in these CRF02/A1 recombinants were similar to those in prototype CRF02 viruses, indicating that recombination at these sites more likely generate variable recombinant viruses. The dominance and fast dissemination of new CRF02a/A1 recombinants over prototype CRF02 suggest that these recombinant have more adapted and may become major epidemic strains in Pakistan.
Highlights
Since the first case of AIDS in Pakistan was reported in 1987 [1], the estimated number of people infected with HIV has increased to ~87,000 in 2012 [2, 3]
The infection status could not be determined for PK032 since there was not enough plasma available for analysis. These results showed that 31 viruses were collected during chronic HIV-1 infection while two viruses were collected at early infection stage
Like PK020, it clustered tightly together with CRF02 by forming a tight subcluster (CRF02a) sequences in the same third CRF02-like subtype A region (Figs 2E and 3). These results demonstrated that both PK020 and PK033 were recombinants; while the most parts of PK020 and PK033 genomes were A1b and A1a, respectively, both recombined with CRF02a that had evolved into unique Pakistan-specific virus population at middle of the viral genome
Summary
Since the first case of AIDS in Pakistan was reported in 1987 [1], the estimated number of people infected with HIV has increased to ~87,000 in 2012 [2, 3]. Like other Asia countries, Pakistan experiences a comparable HIV epidemic trend from “low prevalence, high risk” to “concentrated” epidemic in the early to mid-2000s [4]. Pakistan currently has a low PLOS ONE | DOI:10.1371/journal.pone.0167839. Pakistan currently has a low PLOS ONE | DOI:10.1371/journal.pone.0167839 December 14, 2016
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