Limits...
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.

Show MeSH

Related in: MedlinePlus

Maximum likelihood analysis and past population dynamics of HIV-1 CRF33_01B disseminating among various risk groups in Southeast Asia (Malaysia and Indonesia).The maximum likelihood reconstruction and past population dynamics of all available CRF33_01B isolates was estimated by PAUP* v4.0 beta [40] and the Bayesian sampling approach implemented in BEAST v1.7 [47], respectively. A total of 242 CRF33_01B sequences (pol region, HXB2∶2253–3260) spanning year 2005–2012 among individuals from various risk groups (inclusive of 152 and 90 sequences with known and unknown transmission risks, respectively) and geographical origins (central, northern and eastern states of Malaysia) and two full-length sequences from Indonesia were analyzed. The data set of CRF33_01Bpol sequences were amplified from HIV-1 positive samples collected from the following regions: the central states of Malaysia (n = 142) including Kuala Lumpur (n = 54, including four CRF33_01B reference sequences [21], Selangor (n = 86) and Negeri Sembilan (n = 2); the northern states (n = 85) including Kelantan (n = 79) and Perak (n = 6); and the eastern state (n = 13) of Pahang [22]. Indonesian CRF33_01B reference sequences (n = 2) were retrieved from the online database [27] and included in the analyses. A, Maximum likelihood analysis of CRF33_01Bpol data set containing 152 sequences with known transmission risks revealed a phylogenetic tree with star-like appearance, in which the terminal tree branches (mean length: 0.025±0.014) were in general longer than the internal branches (mean length: 0.005±0.005), possibly suggesting a high growth rate for CRF33_01B during the early phase of the epidemic [48]. In addition, tree topology showed the dissemination of HIV-1 CRF33_01B from PWIDs to other risk groups including the low-risk populations, notably among children who acquired infections through their mothers. B, The Bayesian skyline plot estimated the past population dynamics of CRF33_01B among various risk groups in Malaysia using the CRF33_01Bpol data set of 242 sequences mentioned above (and also in the text). The x-axis represents the time (in units of year) and y-axis represents the effective population size of CRF33_01B. The thick solid line in the plot represents the median estimate and the shaded region represents the 95% highest posterior density (HPD) credible region. The Bayesian skyline plot revealed an exponential increase in effective number of CRF33_01B infections in the host population since its reported emergence around 1991 to 1993 [31] until early 2000s and remained stable thereafter at a high prevalence, suggesting persistent viral transmission and endemicity of CRF33_01B among various risk groups in Malaysia.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3646884&req=5

pone-0062560-g004: Maximum likelihood analysis and past population dynamics of HIV-1 CRF33_01B disseminating among various risk groups in Southeast Asia (Malaysia and Indonesia).The maximum likelihood reconstruction and past population dynamics of all available CRF33_01B isolates was estimated by PAUP* v4.0 beta [40] and the Bayesian sampling approach implemented in BEAST v1.7 [47], respectively. A total of 242 CRF33_01B sequences (pol region, HXB2∶2253–3260) spanning year 2005–2012 among individuals from various risk groups (inclusive of 152 and 90 sequences with known and unknown transmission risks, respectively) and geographical origins (central, northern and eastern states of Malaysia) and two full-length sequences from Indonesia were analyzed. The data set of CRF33_01Bpol sequences were amplified from HIV-1 positive samples collected from the following regions: the central states of Malaysia (n = 142) including Kuala Lumpur (n = 54, including four CRF33_01B reference sequences [21], Selangor (n = 86) and Negeri Sembilan (n = 2); the northern states (n = 85) including Kelantan (n = 79) and Perak (n = 6); and the eastern state (n = 13) of Pahang [22]. Indonesian CRF33_01B reference sequences (n = 2) were retrieved from the online database [27] and included in the analyses. A, Maximum likelihood analysis of CRF33_01Bpol data set containing 152 sequences with known transmission risks revealed a phylogenetic tree with star-like appearance, in which the terminal tree branches (mean length: 0.025±0.014) were in general longer than the internal branches (mean length: 0.005±0.005), possibly suggesting a high growth rate for CRF33_01B during the early phase of the epidemic [48]. In addition, tree topology showed the dissemination of HIV-1 CRF33_01B from PWIDs to other risk groups including the low-risk populations, notably among children who acquired infections through their mothers. B, The Bayesian skyline plot estimated the past population dynamics of CRF33_01B among various risk groups in Malaysia using the CRF33_01Bpol data set of 242 sequences mentioned above (and also in the text). The x-axis represents the time (in units of year) and y-axis represents the effective population size of CRF33_01B. The thick solid line in the plot represents the median estimate and the shaded region represents the 95% highest posterior density (HPD) credible region. The Bayesian skyline plot revealed an exponential increase in effective number of CRF33_01B infections in the host population since its reported emergence around 1991 to 1993 [31] until early 2000s and remained stable thereafter at a high prevalence, suggesting persistent viral transmission and endemicity of CRF33_01B among various risk groups in Malaysia.

Mentions: Genealogy-based maximum likelihood analysis of CRF33_01Bpol data set containing 152 sequences with known transmission risks revealed a phylogenetic tree with star-like appearance in which the terminal tree branches (mean length: 0.025±0.014) were in general longer than the internal branches (mean length: 0.005±0.005) (Figure 4A). A number of CRF33_01B sub-lineages were observed, with isolates from the PWIDs predominantly sampled from the central states located at the base of these lineages showing apparent founder effect. Of note, internal nodes of CRF33_01B sequences from pediatric subjects who acquired infection from their mothers were positioned near the terminal or the tip of the tree. Next, in order to investigate the demographic history of CRF33_01B infections in Malaysia, specifically the past population dynamics, we estimated the effective population sizes of CRF33_01B through time by generating a Bayesian skyline plot using a total of 242 CRF33_01Bpol data set (inclusive of 90 sequences with unknown transmission risks) (Figure 4B). From the plot, it was observed that the effective population size of CRF33_01B had remained significantly high since early 2000s for almost a decade, suggesting that the virus had established itself among various risk groups in the HIV-infected population along with other main circulating genotypes - CRF01_AE and subtype B′ in Malaysia. The plot correlated well with our current epidemiological finding reported in this study where CRF33_01B was massively expanding in the PWIDs 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)

Maximum likelihood analysis and past population dynamics of HIV-1 CRF33_01B disseminating among various risk groups in Southeast Asia (Malaysia and Indonesia).The maximum likelihood reconstruction and past population dynamics of all available CRF33_01B isolates was estimated by PAUP* v4.0 beta [40] and the Bayesian sampling approach implemented in BEAST v1.7 [47], respectively. A total of 242 CRF33_01B sequences (pol region, HXB2∶2253–3260) spanning year 2005–2012 among individuals from various risk groups (inclusive of 152 and 90 sequences with known and unknown transmission risks, respectively) and geographical origins (central, northern and eastern states of Malaysia) and two full-length sequences from Indonesia were analyzed. The data set of CRF33_01Bpol sequences were amplified from HIV-1 positive samples collected from the following regions: the central states of Malaysia (n = 142) including Kuala Lumpur (n = 54, including four CRF33_01B reference sequences [21], Selangor (n = 86) and Negeri Sembilan (n = 2); the northern states (n = 85) including Kelantan (n = 79) and Perak (n = 6); and the eastern state (n = 13) of Pahang [22]. Indonesian CRF33_01B reference sequences (n = 2) were retrieved from the online database [27] and included in the analyses. A, Maximum likelihood analysis of CRF33_01Bpol data set containing 152 sequences with known transmission risks revealed a phylogenetic tree with star-like appearance, in which the terminal tree branches (mean length: 0.025±0.014) were in general longer than the internal branches (mean length: 0.005±0.005), possibly suggesting a high growth rate for CRF33_01B during the early phase of the epidemic [48]. In addition, tree topology showed the dissemination of HIV-1 CRF33_01B from PWIDs to other risk groups including the low-risk populations, notably among children who acquired infections through their mothers. B, The Bayesian skyline plot estimated the past population dynamics of CRF33_01B among various risk groups in Malaysia using the CRF33_01Bpol data set of 242 sequences mentioned above (and also in the text). The x-axis represents the time (in units of year) and y-axis represents the effective population size of CRF33_01B. The thick solid line in the plot represents the median estimate and the shaded region represents the 95% highest posterior density (HPD) credible region. The Bayesian skyline plot revealed an exponential increase in effective number of CRF33_01B infections in the host population since its reported emergence around 1991 to 1993 [31] until early 2000s and remained stable thereafter at a high prevalence, suggesting persistent viral transmission and endemicity of CRF33_01B among various risk groups in Malaysia.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0062560-g004: Maximum likelihood analysis and past population dynamics of HIV-1 CRF33_01B disseminating among various risk groups in Southeast Asia (Malaysia and Indonesia).The maximum likelihood reconstruction and past population dynamics of all available CRF33_01B isolates was estimated by PAUP* v4.0 beta [40] and the Bayesian sampling approach implemented in BEAST v1.7 [47], respectively. A total of 242 CRF33_01B sequences (pol region, HXB2∶2253–3260) spanning year 2005–2012 among individuals from various risk groups (inclusive of 152 and 90 sequences with known and unknown transmission risks, respectively) and geographical origins (central, northern and eastern states of Malaysia) and two full-length sequences from Indonesia were analyzed. The data set of CRF33_01Bpol sequences were amplified from HIV-1 positive samples collected from the following regions: the central states of Malaysia (n = 142) including Kuala Lumpur (n = 54, including four CRF33_01B reference sequences [21], Selangor (n = 86) and Negeri Sembilan (n = 2); the northern states (n = 85) including Kelantan (n = 79) and Perak (n = 6); and the eastern state (n = 13) of Pahang [22]. Indonesian CRF33_01B reference sequences (n = 2) were retrieved from the online database [27] and included in the analyses. A, Maximum likelihood analysis of CRF33_01Bpol data set containing 152 sequences with known transmission risks revealed a phylogenetic tree with star-like appearance, in which the terminal tree branches (mean length: 0.025±0.014) were in general longer than the internal branches (mean length: 0.005±0.005), possibly suggesting a high growth rate for CRF33_01B during the early phase of the epidemic [48]. In addition, tree topology showed the dissemination of HIV-1 CRF33_01B from PWIDs to other risk groups including the low-risk populations, notably among children who acquired infections through their mothers. B, The Bayesian skyline plot estimated the past population dynamics of CRF33_01B among various risk groups in Malaysia using the CRF33_01Bpol data set of 242 sequences mentioned above (and also in the text). The x-axis represents the time (in units of year) and y-axis represents the effective population size of CRF33_01B. The thick solid line in the plot represents the median estimate and the shaded region represents the 95% highest posterior density (HPD) credible region. The Bayesian skyline plot revealed an exponential increase in effective number of CRF33_01B infections in the host population since its reported emergence around 1991 to 1993 [31] until early 2000s and remained stable thereafter at a high prevalence, suggesting persistent viral transmission and endemicity of CRF33_01B among various risk groups in Malaysia.
Mentions: Genealogy-based maximum likelihood analysis of CRF33_01Bpol data set containing 152 sequences with known transmission risks revealed a phylogenetic tree with star-like appearance in which the terminal tree branches (mean length: 0.025±0.014) were in general longer than the internal branches (mean length: 0.005±0.005) (Figure 4A). A number of CRF33_01B sub-lineages were observed, with isolates from the PWIDs predominantly sampled from the central states located at the base of these lineages showing apparent founder effect. Of note, internal nodes of CRF33_01B sequences from pediatric subjects who acquired infection from their mothers were positioned near the terminal or the tip of the tree. Next, in order to investigate the demographic history of CRF33_01B infections in Malaysia, specifically the past population dynamics, we estimated the effective population sizes of CRF33_01B through time by generating a Bayesian skyline plot using a total of 242 CRF33_01Bpol data set (inclusive of 90 sequences with unknown transmission risks) (Figure 4B). From the plot, it was observed that the effective population size of CRF33_01B had remained significantly high since early 2000s for almost a decade, suggesting that the virus had established itself among various risk groups in the HIV-infected population along with other main circulating genotypes - CRF01_AE and subtype B′ in Malaysia. The plot correlated well with our current epidemiological finding reported in this study where CRF33_01B was massively expanding in the PWIDs 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