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Molecular diversity of HIV-1 among people who inject drugs in Kuala Lumpur, Malaysia: massive expansion of circulating recombinant form (CRF) 33_01B and emergence of multiple unique recombinant clusters.

Chow WZ, Ong LY, Razak SH, Lee YM, Ng KT, Yong YK, Azmel A, Takebe Y, Al-Darraji HA, Kamarulzaman A, Tee KK - PLoS ONE (2013)

Bottom Line: Using rigorous maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC) sampling of CRF33_01Bpol sequences to elucidate the past population dynamics, we found that the founder lineages of CRF33_01B were likely to have first emerged among PWIDs in the early 1990 s before spreading exponentially to various high and low-risk populations (including children who acquired infections from their mothers) and later on became endemic around the early 2000 s.Taken together, our findings provide notable genetic evidence indicating the widespread expansion of CRF33_01B among PWIDs and into the general population.The emergence of numerous previously unknown recombinant clades highlights the escalating genetic complexity of HIV-1 in the Southeast Asian region.

View Article: PubMed Central - PubMed

Affiliation: Centre of Excellence for Research in AIDS (CERiA), Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

ABSTRACT
Since the discovery of HIV-1 circulating recombinant form (CRF) 33_01B in Malaysia in the early 2000 s, continuous genetic diversification and active recombination involving CRF33_01B and other circulating genotypes in the region including CRF01_AE and subtype B' of Thai origin, have led to the emergence of novel CRFs and unique recombinant forms. The history and magnitude of CRF33_01B transmission among various risk groups including people who inject drugs (PWID) however have not been investigated despite the high epidemiological impact of CRF33_01B in the region. We update the most recent molecular epidemiology of HIV-1 among PWIDs recruited in Malaysia between 2010 and 2011 by population sequencing and phylogenetic analysis of 128 gag-pol sequences. HIV-1 CRF33_01B was circulating among 71% of PWIDs whilst a lower prevalence of other previously dominant HIV-1 genotypes [subtype B' (11%) and CRF01_AE (5%)] and CRF01_AE/B' unique recombinants (13%) were detected, indicating a significant shift in genotype replacement in this population. Three clusters of CRF01_AE/B' recombinants displaying divergent yet phylogenetically-related mosaic genomes to CRF33_01B were identified and characterized, suggestive of an abrupt emergence of multiple novel CRF clades. Using rigorous maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC) sampling of CRF33_01Bpol sequences to elucidate the past population dynamics, we found that the founder lineages of CRF33_01B were likely to have first emerged among PWIDs in the early 1990 s before spreading exponentially to various high and low-risk populations (including children who acquired infections from their mothers) and later on became endemic around the early 2000 s. Taken together, our findings provide notable genetic evidence indicating the widespread expansion of CRF33_01B among PWIDs and into the general population. The emergence of numerous previously unknown recombinant clades highlights the escalating genetic complexity of HIV-1 in the Southeast Asian region.

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Related in: MedlinePlus

Phylogenetic analysis of the 1.6 kb HIV-1 gag-pol sequences (HXB2∶1753–3440) amplified among people who inject drugs (PWID) in Kuala Lumpur, Malaysia.The gag-pol genes (n = 98) were sequenced, codon-aligned and manually adjusted with the HIV-1 reference subtypes and circulating recombinant forms (CRFs) retrieved from the Los Alamos HIV database (http://www.hiv.lanl.gov/). Neighbour-joining tree was constructed in MEGA 5.05 [34] using Kimura 2-parameter method of nucleotide substitutions to estimate pair-wise evolutionary distance and the reliability of the branching nodes were assessed by bootstrap analysis of 1000 replicates. Reference strains of established and informative HIV-1 genotypes – CRF01_AE, subtype B (including Thai B′), CRF15_01B, CRF34_01B CRF33_01B, CRF48_01B, CRF51_01B, CRF52_01B and other relevant unique recombinant forms (URFs) circulating in Southeast Asia were also included in the analysis to improve tree resolution. Other HIV-1 genotypes – subtypes C, D and SIVcpz reference strains (CPZ.US_MARILYN and CPZ.SIVcpzCAM13) were included as outgroup. The newly emerged unique recombinant clusters identified in this study were highlighted as CRF candidate 1 (10MYKJ036, 11MY1RJ704, 11MY1ZK731 and 11MY1EP794), CRF candidate 2 (10MYKJ067, 10MYKJ079 and 04MYKL016) and CRF candidate 3 (10MYKJ016, 10MYKJ052, 11MY1YC672 and 11MY1JJ741). Bootstrap values of greater than 70% were indicated on the branch nodes. The scale bar represents 2% genetic distance (0.02 substitutions per site).
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pone-0062560-g001: Phylogenetic analysis of the 1.6 kb HIV-1 gag-pol sequences (HXB2∶1753–3440) amplified among people who inject drugs (PWID) in Kuala Lumpur, Malaysia.The gag-pol genes (n = 98) were sequenced, codon-aligned and manually adjusted with the HIV-1 reference subtypes and circulating recombinant forms (CRFs) retrieved from the Los Alamos HIV database (http://www.hiv.lanl.gov/). Neighbour-joining tree was constructed in MEGA 5.05 [34] using Kimura 2-parameter method of nucleotide substitutions to estimate pair-wise evolutionary distance and the reliability of the branching nodes were assessed by bootstrap analysis of 1000 replicates. Reference strains of established and informative HIV-1 genotypes – CRF01_AE, subtype B (including Thai B′), CRF15_01B, CRF34_01B CRF33_01B, CRF48_01B, CRF51_01B, CRF52_01B and other relevant unique recombinant forms (URFs) circulating in Southeast Asia were also included in the analysis to improve tree resolution. Other HIV-1 genotypes – subtypes C, D and SIVcpz reference strains (CPZ.US_MARILYN and CPZ.SIVcpzCAM13) were included as outgroup. The newly emerged unique recombinant clusters identified in this study were highlighted as CRF candidate 1 (10MYKJ036, 11MY1RJ704, 11MY1ZK731 and 11MY1EP794), CRF candidate 2 (10MYKJ067, 10MYKJ079 and 04MYKL016) and CRF candidate 3 (10MYKJ016, 10MYKJ052, 11MY1YC672 and 11MY1JJ741). Bootstrap values of greater than 70% were indicated on the branch nodes. The scale bar represents 2% genetic distance (0.02 substitutions per site).

Mentions: Based on neighbour-joining phylogenetic reconstructions of the gag-pol genes (Figure 1) and other partial gag-PR and RT genes (Figure S1a and S1b), 71% (91/128) of PWIDs isolates were grouped with the HIV-1 CRF33_01B reference sequences from the database, indicating a high prevalence of CRF33_01B circulating in the study population. HIV-1 CRF01_AE/B recombinants were detected at 13% (16/128) (described in detail below). This is followed by a lower prevalence rate of other established HIV-1 genotypes circulating in the region – subtype B′ and CRF01_AE attributing to 11% (14/128) and 5% (7/128), respectively of the HIV-1 infections among PWIDs. Unlike HIV-1 subtype B′ of Thai origin, western lineages of subtype B were not identified among the PWIDs in this study. Likewise, other previously described CRFs in Southeast Asia such as CRF15_01B, CRF34_01B, CRF48_01B, CRF51_01B and CRF52_01B were also not detected in the study population.


Molecular diversity of HIV-1 among people who inject drugs in Kuala Lumpur, Malaysia: massive expansion of circulating recombinant form (CRF) 33_01B and emergence of multiple unique recombinant clusters.

Chow WZ, Ong LY, Razak SH, Lee YM, Ng KT, Yong YK, Azmel A, Takebe Y, Al-Darraji HA, Kamarulzaman A, Tee KK - PLoS ONE (2013)

Phylogenetic analysis of the 1.6 kb HIV-1 gag-pol sequences (HXB2∶1753–3440) amplified among people who inject drugs (PWID) in Kuala Lumpur, Malaysia.The gag-pol genes (n = 98) were sequenced, codon-aligned and manually adjusted with the HIV-1 reference subtypes and circulating recombinant forms (CRFs) retrieved from the Los Alamos HIV database (http://www.hiv.lanl.gov/). Neighbour-joining tree was constructed in MEGA 5.05 [34] using Kimura 2-parameter method of nucleotide substitutions to estimate pair-wise evolutionary distance and the reliability of the branching nodes were assessed by bootstrap analysis of 1000 replicates. Reference strains of established and informative HIV-1 genotypes – CRF01_AE, subtype B (including Thai B′), CRF15_01B, CRF34_01B CRF33_01B, CRF48_01B, CRF51_01B, CRF52_01B and other relevant unique recombinant forms (URFs) circulating in Southeast Asia were also included in the analysis to improve tree resolution. Other HIV-1 genotypes – subtypes C, D and SIVcpz reference strains (CPZ.US_MARILYN and CPZ.SIVcpzCAM13) were included as outgroup. The newly emerged unique recombinant clusters identified in this study were highlighted as CRF candidate 1 (10MYKJ036, 11MY1RJ704, 11MY1ZK731 and 11MY1EP794), CRF candidate 2 (10MYKJ067, 10MYKJ079 and 04MYKL016) and CRF candidate 3 (10MYKJ016, 10MYKJ052, 11MY1YC672 and 11MY1JJ741). Bootstrap values of greater than 70% were indicated on the branch nodes. The scale bar represents 2% genetic distance (0.02 substitutions per site).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3646884&req=5

pone-0062560-g001: Phylogenetic analysis of the 1.6 kb HIV-1 gag-pol sequences (HXB2∶1753–3440) amplified among people who inject drugs (PWID) in Kuala Lumpur, Malaysia.The gag-pol genes (n = 98) were sequenced, codon-aligned and manually adjusted with the HIV-1 reference subtypes and circulating recombinant forms (CRFs) retrieved from the Los Alamos HIV database (http://www.hiv.lanl.gov/). Neighbour-joining tree was constructed in MEGA 5.05 [34] using Kimura 2-parameter method of nucleotide substitutions to estimate pair-wise evolutionary distance and the reliability of the branching nodes were assessed by bootstrap analysis of 1000 replicates. Reference strains of established and informative HIV-1 genotypes – CRF01_AE, subtype B (including Thai B′), CRF15_01B, CRF34_01B CRF33_01B, CRF48_01B, CRF51_01B, CRF52_01B and other relevant unique recombinant forms (URFs) circulating in Southeast Asia were also included in the analysis to improve tree resolution. Other HIV-1 genotypes – subtypes C, D and SIVcpz reference strains (CPZ.US_MARILYN and CPZ.SIVcpzCAM13) were included as outgroup. The newly emerged unique recombinant clusters identified in this study were highlighted as CRF candidate 1 (10MYKJ036, 11MY1RJ704, 11MY1ZK731 and 11MY1EP794), CRF candidate 2 (10MYKJ067, 10MYKJ079 and 04MYKL016) and CRF candidate 3 (10MYKJ016, 10MYKJ052, 11MY1YC672 and 11MY1JJ741). Bootstrap values of greater than 70% were indicated on the branch nodes. The scale bar represents 2% genetic distance (0.02 substitutions per site).
Mentions: Based on neighbour-joining phylogenetic reconstructions of the gag-pol genes (Figure 1) and other partial gag-PR and RT genes (Figure S1a and S1b), 71% (91/128) of PWIDs isolates were grouped with the HIV-1 CRF33_01B reference sequences from the database, indicating a high prevalence of CRF33_01B circulating in the study population. HIV-1 CRF01_AE/B recombinants were detected at 13% (16/128) (described in detail below). This is followed by a lower prevalence rate of other established HIV-1 genotypes circulating in the region – subtype B′ and CRF01_AE attributing to 11% (14/128) and 5% (7/128), respectively of the HIV-1 infections among PWIDs. Unlike HIV-1 subtype B′ of Thai origin, western lineages of subtype B were not identified among the PWIDs in this study. Likewise, other previously described CRFs in Southeast Asia such as CRF15_01B, CRF34_01B, CRF48_01B, CRF51_01B and CRF52_01B were also not detected in the study population.

Bottom Line: Using rigorous maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC) sampling of CRF33_01Bpol sequences to elucidate the past population dynamics, we found that the founder lineages of CRF33_01B were likely to have first emerged among PWIDs in the early 1990 s before spreading exponentially to various high and low-risk populations (including children who acquired infections from their mothers) and later on became endemic around the early 2000 s.Taken together, our findings provide notable genetic evidence indicating the widespread expansion of CRF33_01B among PWIDs and into the general population.The emergence of numerous previously unknown recombinant clades highlights the escalating genetic complexity of HIV-1 in the Southeast Asian region.

View Article: PubMed Central - PubMed

Affiliation: Centre of Excellence for Research in AIDS (CERiA), Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

ABSTRACT
Since the discovery of HIV-1 circulating recombinant form (CRF) 33_01B in Malaysia in the early 2000 s, continuous genetic diversification and active recombination involving CRF33_01B and other circulating genotypes in the region including CRF01_AE and subtype B' of Thai origin, have led to the emergence of novel CRFs and unique recombinant forms. The history and magnitude of CRF33_01B transmission among various risk groups including people who inject drugs (PWID) however have not been investigated despite the high epidemiological impact of CRF33_01B in the region. We update the most recent molecular epidemiology of HIV-1 among PWIDs recruited in Malaysia between 2010 and 2011 by population sequencing and phylogenetic analysis of 128 gag-pol sequences. HIV-1 CRF33_01B was circulating among 71% of PWIDs whilst a lower prevalence of other previously dominant HIV-1 genotypes [subtype B' (11%) and CRF01_AE (5%)] and CRF01_AE/B' unique recombinants (13%) were detected, indicating a significant shift in genotype replacement in this population. Three clusters of CRF01_AE/B' recombinants displaying divergent yet phylogenetically-related mosaic genomes to CRF33_01B were identified and characterized, suggestive of an abrupt emergence of multiple novel CRF clades. Using rigorous maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC) sampling of CRF33_01Bpol sequences to elucidate the past population dynamics, we found that the founder lineages of CRF33_01B were likely to have first emerged among PWIDs in the early 1990 s before spreading exponentially to various high and low-risk populations (including children who acquired infections from their mothers) and later on became endemic around the early 2000 s. Taken together, our findings provide notable genetic evidence indicating the widespread expansion of CRF33_01B among PWIDs and into the general population. The emergence of numerous previously unknown recombinant clades highlights the escalating genetic complexity of HIV-1 in the Southeast Asian region.

Show MeSH
Related in: MedlinePlus