Genetic Characterization of a Novel HIV-1 Circulating Recombinant Form (CRF74_01B) Identified among Intravenous Drug Users in Malaysia: Recombination History and Phylogenetic Linkage with Previously Defined Recombinant Lineages.

Jack Bee Chook,Kok Gan Chan,Clayton Koh,Hui Ting Cheong,Haider Abdulrazzaq Abed Al-Darraji,Adeeba Kamarulzaman,Wei Zhen Chow,Kok Keng Tee,Yutaka Takebe

doi:10.1371/journal.pone.0133883

Abstract

In many parts of Southeast Asia, the HIV-1 epidemic has been driven by the sharing of needles and equipment among intravenous drug users (IDUs). Over the last few decades, many studies have proven time and again that the diversity of HIV-1 epidemics can often be linked to the route of infection transmission. That said, the diversity and complexity of HIV-1 molecular epidemics in the region have been increasing at an alarming rate, due in part to the high tendency of the viral RNA to recombine. This scenario was exemplified by the discovery of numerous circulating recombinant forms (CRFs), especially in Thailand and Malaysia. In this study, we characterized a novel CRF designated CRF74_01B, which was identified in six epidemiologically unlinked IDUs in Kuala Lumpur, Malaysia. The near-full length genomes were composed of CRF01_AE and subtype B', with eight breakpoints dispersed in the gag-pol and nef regions. Remarkably, this CRF shared four and two recombination hotspots with the previously described CRF33_01B and the less prevalent CRF53_01B, respectively. Genealogy-based Bayesian phylogenetic analysis of CRF74_01B genomic regions showed that it is closely related to both CRF33_01B and CRF53_01B. This observation suggests that CRF74_01B was probably a direct descendent from specific lineages of CRF33_01B, CRF53_01B and subtype Bʹ that could have emerged in the mid-1990s. Additionally, it illustrated the active recombination processes between prevalent HIV-1 subtypes and recombinants in Malaysia. In summary, we report a novel HIV-1 genotype designated CRF74_01B among IDUs in Kuala Lumpur, Malaysia. The characterization of the novel CRF74_01B is of considerable significance towards the understanding of the genetic diversity and population dynamics of HIV-1 circulating in the region.

Highlights

Group M, the pandemic branch of HIV-1 can be classified into different subtypes named A-D, F-H, J and K
Recombinant lineages generated through recombination between subtypes isolated from at least three epidemiologically unlinked individuals are known as circulating recombinant forms (CRFs), else these recombinants would be known as unique recombinant forms (URFs) [1]
A total of six isolates from epidemiologically-unlinked individuals formed a monophyletic cluster based on phylogenetic analysis of the protease-reverse transcriptase (PRRT) sequences reported previously [11]

Summary

Introduction

Group M, the pandemic branch of HIV-1 can be classified into different subtypes named A-D, F-H, J and K. Numerous HIV-1 CRFs such as CRF33_01B, CRF48_01B, CRF52_01B, CRF53_01B, CRF54_01B, and CRF58_01B have been reported in Malaysia in the past decade [5,6,7,8,9,10], all of which have arisen from the predominant subtype B' and CRF01_AE co-circulating in the country. These new CRFs could further recombine with other subtypes or CRFs, generating second-generation recombinant descendants. We described a novel CRF candidate discovered among IDUs in Malaysia

Methods

Results

Conclusion