Characterization of HIV-1 CRF02_AG/A3/G unique recombinant forms identified among children in Larkana, Pakistan

Front Cell Infect Microbiol. 2023 Oct 30:13:1284815. doi: 10.3389/fcimb.2023.1284815. eCollection 2023.

Abstract

Co-circulation of different human immunodeficiency virus type 1 HIV-1 subtypes among infected populations can lead to the generation of new recombinants. In Pakistan, subtype A1 and CRF02_AG are the dominant strains circulating among key populations. The high prevalence of new HIV infections among the key populations highlights the possibility of recombination between the dominant strains, which can lead to the generation of new recombinants. Here, we identified a recombinant cluster composed of CRF02_AG, sub-subtype A3, and subtype G among HIV-infected children in Larkana. For the study, 10 retrospectively collected samples, with recombination signals in the pol gene, were used to perform a near full-length genome NFLG sequencing. Of the 10 samples, NFLG was successfully sequenced from seven samples. Phylogenetic analysis of the seven NFLGs showed that all recombinants formed a distinct monophyletic cluster and were distinct from known HIV-1 circulating recombinant forms CRFs. Recombination analyses showed that all seven NFLGs shared a similar recombinant structure consisting of CRF02_AG, sub-subtype A3, and subtype G, with a sub-subtype A3 fragment inserted into pol and vif regions spanning from (HXB2: 4218-5518), and a subtype G fragment inserted into vpu, rev, tat and env regions spanning from (HXB2: 5957-8250) of the CRF02_AG backbone. The identification of unique recombinant forms may indicate the presence and transmission of several co-circulating lineages in Larkana, giving rise to newer CRFs. This study also highlights the importance of continuous molecular surveillance to fully understand HIV-1 genetic diversity in Pakistan, particularly in Larkana, which is the epicenter of HIV outbreaks.

Keywords: HIV-1; Larkana; Pakistan; children; genetic recombination; phylogeny.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Genotype
  • HIV Infections* / epidemiology
  • HIV-1* / genetics
  • Humans
  • Pakistan / epidemiology
  • Phylogeny
  • Recombination, Genetic
  • Retrospective Studies

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Science Priority Grant 2019SKLID602 and 2021SKLID303 from the State Key Laboratory of Infections Disease Prevention and Control, Ministry of Science and Technology of China (2012ZX10004910 and 2022YFC2305201), and National Natural Science Foundation International/Inter-Organization Cooperation and Exchange Study-NSFC-VR Project (China and Switzerland) (grant number 81861138011).