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

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.

Extensive Genetic Diversity of HIV-1 in Incident and Prevalent Infections among Malaysian Blood Donors: Multiple Introductions of HIV-1 Genotypes from Highly Prevalent Countries

“…Of note, we also observed an increased frequency of CRF54_01B (around 4%) which was previously described at a lower frequency among various risk populations [13,18], indicating the establishment of CRF54_01B in the general population and its possible expansion as one of the major recombinant genotypes in the country. On the other hand, at least three previously identified genetic clades of CRFs which share structural and evolutionary relationship with CRF33_01B, including CRF48_01B, CRF53_01B and CRF74_01B, continue to circulate at a lower prevalence (<2%), similar to earlier reports [19,20,27]. In fact, the co-circulation of CRF01_AE, CRF33_01B, and subtype B' continues to spur the increasingly complex genetic diversity of HIV-1 in Kuala Lumpur [15,28], as evident in the newly characterised CRF01_AE/B' recombinants (13MYNBB034 and 14MYNBB230) which share at least two identical recombination breakpoints with CRF33_01B in the partial gag-pol genes, and other unique CRF01_AE/B' recombinants with distinct recombination structures (13MYNBB048, 13MYNBB128, 13MYNBB059 and 14MYNBB193).…”

“…More detailed analyses are nonetheless necessary to better understand the recombinant lineage. The availability of the full length genomes will allow the classification of the Malaysian B'/C URFs as a novel CRF lineage [ 40 ], and subsequently enable a more comprehensive phylodynamic mapping to identify the origin and transmission dynamics of the lineage within and between countries in the region [ 20 ].…”

“…Although CRF33_01B co-circulated among various risk populations in the country [ 14 ], it has been recently reported to be highly prevalent among the PWIDs [ 15 ]. Recently, at least five newly emerging clades of HIV-1 genetic variants circulating at a lower prevalence have been characterised in the country, namely CRF52_01B, CRF53_01B, CRF54_01B, CRF58_01B and CRF74_01B [ 16 – 20 ]. In addition, the continuous genetic recombination involving CRF01_AE and subtype B has also resulted in the emergence of various unique recombinant forms (URFs) displaying distinct mosaic recombination structures in the region [ 13 , 15 , 21 ].…”

Análisis genético de las mutaciones presentes en las poblaciones virales en pacientes con infección por VIH-1 en Ecuador

“…La relevancia de conocer el subtipo viral es que algunos subtipos han sido relacionados con algunas vías de transmisión; por ejemplo, el subtipo B se asocia con los hombres que tienen sexo con hombres, así como algunas formas recombinantes con el uso de drogas intravenosas 27,28 . Además, se han descrito mutaciones que generan resistencia en algunos subtipos y no en otros (la 30 y la 90 para IP, la 106 para ITRNAN, etc.)…”

Genome Sequence of Complex HIV-1 Unique Recombinant Forms Sharing a Common Recombination Breakpoint Identified in Malaysia

“…As of 2015, more than 70 circulating recombinant forms (CRFs) have been identified globally ( http://www.hiv.lanl.gov/ ). In Malaysia, various HIV-1 CRFs such as CRF33_01B, CRF48_01B, CRF52_01B, CRF53_01B, CRF54_01B, CRF58_01B, and CRF74_01B ( 2 – 8 ) have been described in the past decade. In this study, we determined three near-full length genomes of unique recombinant forms (URFs), designated 08MYKL056, 10MYKJ086, and 10MYPR70, and found that they share one unique recombination breakpoint in the genome.…”