Phylodynamics of the major HIV-1 CRF02_AG African lineages and its global dissemination

The HIV-1 CRF02_AG clade is the most prevalent HIV variant in West and West-Central Africa and its detection outside Africa is increasingly common. Little is known, however, about the number and phylodynamics of major CRF02_AG lineages circulating worldwide. To this end, a total of 3170 HIV-1 CRF02_AG-like pol sequences isolated around the world, over a period of 25 years (1989 to 2013), were analyzed using Maximum Likelihood and Bayesian coalescent-based methods. Our results suggest that most of the current CRF02_AG diversity comes from the dissemination of a few founder strains out of Central Africa into West Africa and Cameroon between the late 1960s and the middle 1980s. The CRF02_AG strain introduced into West Africa established a large regional epidemic with low phylogeographic structure. This strain was also successfully disseminated out of the West African region and originated at least three large secondary outbreaks in Cameroon at around the late 1970s, in the former Soviet Union (FSU) countries at around the late 1990s, and in Bulgaria/Germany at around the early 2000s. The CRF02_AG African lineages introduced into Cameroon remained mostly restricted to this country and its neighbors. Demographic reconstructions indicate that major CRF02_AG clades circulating in Africa exhibited a decline in growth rate since the middle 1980s/1990s, whereas CRF02_AG clades in Europe and the FSU countries continue to grow exponentially until the middle to late 2000s. Substantial differences in the median estimated growth rate of the same CRF02_AG clade circulating in different regions (0.63–2.00 year^− 1), and of different CRF02_AG clades circulating in the same country (0.41–0.75 year^− 1) were observed. Thus, the cause of the epidemic outcome of the different HIV-1 CRF02_AG lineages is probably multifactorial.     

Reconstructing the HIV-1 CRF02_AG and CRF06_cpx epidemics in Burkina Faso and West Africa using early samples

BackgroundHIV-1 circulating recombinant forms (CRFs) represent viral recombinant lineages that play a significant role in the global epidemic. Two of them dominate the epidemic in Burkina Faso: CRF06_cpx (first described in this country) and CRF02_AG. We reconstructed the phylodynamics of both recombinant viruses in Burkina Faso and throughout West Africa.MethodsWe analysed CRF06_cpx and CRF02_AG sequences (protease/gp41) from early samples collected in Burkina Faso in 1986 together with other GenBank sequences (1984–2013) in 4 datasets: African CRF06_cpx (210/60); down-sampled CRF06_cpx (146/45); Burkina Faso CRF02_AG (130/39) and West/Central African CRF02_AG (691/298). For each dataset, we analysed both protease and gp41 jointly using the BEAST multilocus analysis and conducted phylogeographic analysis to reconstruct the early migration routes between countries.ResultsThe time to the most recent common ancestor (tMRCA) of CRF06_cpx was 1979 (1973–1983) for protease and 1981 (1978–1983) for gp41. The gp41 analysis inferred the origin of CRF06_cpx (or at least its parental subtype G lineage) in the Democratic Republic of Congo but migrated to Burkina Faso soon after (1982). Both genes showed that CRF06_cpx radiated to the rest of West Africa predominantly after around 1990. These results were robust to the oversampling of Burkina Faso sequences as they were confirmed in the down-sampled dataset. The tMRCA of the Burkina Faso CRF02_AG lineage was 1979 (1977–1983) for protease and 1980 (1978–1981) for gp41. However, we reconstructed its presence in West Africa much earlier (mid-1960s), with an initial origin in Cameroon and/or Nigeria, and its phylogeographic analysis revealed much interconnection within the region with a lack of country-specific phylogenetic patterns, which prevents tracking its exact migration routes.ConclusionsBurkina Faso presents a relatively young HIV epidemic, with the diversification of the current in-country CRF02_AG and CRF06_cpx lineages taking place around 1980. This country represents the main source of CRF06_cpx in West Africa. The CRF02_AG epidemic started at least a decade earlier and showed much interchange between West African countries (especially involving coastal countries) suggesting great population mobility and an extensive viral spread in the region.     

Striking lack of T cell immunodominance in both a multiclade and monoclade HIV-1 epidemic: Implications for vaccine development

Understanding the impact of HIV diversity on immunological responses to candidate immunogens is critical for HIV vaccine development. We investigated the reactivity and immunodominance patterns of HIV-1 consensus group M Gag and Nef in (i) Cameroon, where individuals infected with the predominant CRF02_AG clade were compared with those infected with diverse non-CRF02_AG clades; and (ii) in a multiclade epidemic, namely Cameroon, compared with a monoclade C epidemic, South Africa. We analyzed 57 HIV-infected individuals from Cameroon and 44 HIV-infected individuals from South Africa for differences in detecting HIV-1 consensus M Gag and Nef T cell responses using the IFN-γ ELISpot assay. We found no difference in the predicted epitope coverage between CRF02_AG and non-CRF02_AG viruses for either Gag or Nef. There were no differences in the magnitude and breadth of responses for CRF02_AG and non-CRF02_AG-infected individuals. In contrast, the specificity of epitope targeting was markedly different between the two groups, with fewer than one third (11/38) of peptides commonly recognized in Gag. Furthermore, only one peptide was commonly recognized by at least three individuals from both AG and non-AG groups, indicating poor immunodominance. For Nef, more than half of all targeted peptides (14/27) were recognized by both groups, and four peptides were commonly targeted by at least three individuals. Three times more peptides were exclusively targeted in the diverse non-CRF02_AG group compared to the CRF02_AG group (10 vs. 3). Of note, similar results were obtained when South Africa, a monoclade C epidemic, and Cameroon, a multiclade epidemic, were compared. The central nature of HIV-1 consensus M sequences resulted in their broad recognition, but failed to identify highly immunodominant peptides between homogeneous and diverse HIV epidemics.     

Phylogeographic analysis on the travel-related introduction of HIV-1 non-B subtypes to Northern Poland

Phylodynamic, sequence data based reconstructions for the surveillance of the geographic spatial spread are a powerful tool in molecular epidemiology. In this study region of origin for the set of 57 partial pol sequences derived from the patients the history of travel-related HIV transmission was analyzed using phylogeographic approach. Maximum likelihood trees based on the sets of country-annotated reference sequences were inferred for identified non-B variants. Region of sequence import was assigned using on the highest approximate likelihood ratios. Import of the A1 clades was traced to the Eastern Europe and associated with immigration from this region. Subtype C infections clustered most frequently with sequences of the South African origin while majority of subtype Ds were similar to the European clades. Subtype G sequences clustered with Portuguese lineage, CRF01_AE with Eastern or South-Eastern Asian. Eastern European, Middle African or Western African lineage was assigned for the CFR02_AG. Rare circulating recombinants originated either from Central Africa (CRF11_cpx – Democratic Republic of Congo, CRF13_cpx – Central African Republic, CRF37_cpx – Cameroon) or South America (CRF28_BF and CRF46_BF - Brazil). Import of the HIV-1 non-B variants, including recombinant forms previously rarely found in Poland and Europe is frequent among travelers. Observed founder events result in the heterosexually-driven introduction of the novel HIV-1 variants into the population.     

Highly divergent subtypes and new recombinant forms prevail in the HIV/AIDS epidemic in Angola: New insights into the origins of the AIDS pandemic

Angola, located in South-Western Africa, has a remarkably low HIV/AIDS prevalence in the adult population (3.7%). It is bordered in the North by the Democratic Republic of Congo (DRC) and Republic of Congo that are at the origin of human HIV-1 infections. It is, therefore, likely that HIV-1 strains circulating in Angola are genetically diverse and representative of the origin of the HIV/AIDS epidemic. The aim of this work was to investigate in detail the genetic diversity and molecular epidemiology of HIV-1 in Angola. Almost 400 sequences were obtained from the gag (p17), pol (PR and RT) and/or env (C2C3) genes of 159 HIV-1 infected patients living in eight provinces of Angola (Benguela, Cabinda, Cuanza Norte, Luanda, Lunda Norte, Malange, Uíge, and Zaire) and their genotype was determined by phylogenetic analyses. Gene regions representing all HIV-1 group M clades were found as well as unclassifiable sequences. In env and pol (RT), two groups of sequences forming distinct sub-clusters within the subtype A radiation were found and may define new A5 and A6 sub-subtypes. Recombinant forms were found in almost half (47.1%) of the patients of which 36.0% were second-generation recombinants. Fifty-eight different patterns of recombination were found. The A subtype, including CRF02_AG, was represented in most recombinant viruses. Epidemiological data suggests that the AIDS epidemic in Angola has probably started as early as 1961, the major cause being the independence war, and spread to Portugal soon thereafter. The extraordinary degree of HIV-1 group M genetic diversity and evolution in Angola may pose unprecedented challenges to diagnostic, treatment and prevention of HIV-1 infection.     

Viral, HLA and T cell elements in cross-reactive immune responses to HIV-1 subtype A, CRF01_AE and CRF02_AG vaccine sequence in Ivorian blood donors

Comprehensive understanding of the determinants of cross-subtype immune responses in HIV infection is critical to developing efficacious HIV vaccines against multiple viral subtypes. Because HIV-1 subtype A or recombinants comprising subtype A are prevalent in Africa and parts of Asia where HIV is spreading, we assessed the determinants of cross-subtype immune responses in HIV-infected blood donors from Cote d'Ivoire to peptides from a candidate CRF02_AG vaccine sequence, a subtype A sequence from western Kenya and a CRF01_AE sequence from Thailand. We present evidence that immune recognition of multiple viral subtypes is maintained by recognition of multiple epitopes. Our data suggest that complete escape of HIV from immune recognition is uncommon. Evaluation of these frequently generated cross-reactive responses should be included in immunogenicity trials of HIV vaccines.     

Origin and spread of HIV-1 in persons who inject drugs in Bulgaria

Increased HIV transmission in persons who inject drugs (PWIDs) has led to subepidemics and outbreaks in several countries in Europe, including Bulgaria. In this study in Bulgaria, we investigate the origin and spatiotemporal evolutionary history of HIV-1 infections in PWIDs and the distribution of antiretroviral resistance mutations and hepatitis co-infections in these populations. We analyzed HIV-1 polymerase sequences available from 117 of 359 PWIDs diagnosed with HIV/AIDS from 1999 to 2011. Of these, 50 (42.7%) were classified as CRF02_AG, 41 (35.0%) CRF01_AE, 12 (10.3%) URFs, ten (8.5%) subtype B, two (1.7%) subtype F1 and two (1.7%) CRF14_BG. Most recent common ancestor dating suggests that CRF01_AE was likely first introduced from Southeast Asia into persons reporting heterosexual infection in Bulgaria in 1992 and spread subsequently to PWIDs in the capital city of Sofia around 2003. Conversely, CRF02_AG in Bulgaria was likely first introduced into PWID from Germany in 2000 and later entered heterosexual populations around 2009. The overall prevalence of resistance mutations was 6.8% (8/117), of which 5.1% (5/117) was observed in patients on antiretroviral therapy and 1.7% (2/117) was from transmitted drug resistance mutations in drug-naïve individuals. 189/204 (92.6%) PWIDs were also co-infected with hepatitis C (HCV) and 31/183 (16.9%) were co-infected with hepatitis B (HBV). Our study provides valuable molecular epidemiological information on the introduction and distribution of the main HIV-1 subtypes, resistance mutations and hepatitis co-infections among PWIDs with HIV-1 in Bulgaria which can be used to target prevention efforts.     

深圳地区1992--2008年HIV-1分子流行病学研究

目的 了解1992-2008年深圳地区HIV-1亚型的流行特点.方法 抽取1992-2008年深圳地区HIV确认阳性患者血清489份,应用巢式PCR扩增膜蛋白基因(env基因),并对PCR产物进行序列测定和分析.结果 共有464份样本获得分型结果,主要为CRF01 AE亚型(64.4％,299/464),其次是CRF BC( 17.5％,81/464)、B'(14.7％,68/464)和B亚型(2.4％,11/464),还发现C(0.4％,2/464)、A1 (0.2％,1/464)、CRF02_AG(0.2％,1/464)和CRF06_cpx (0.2％,1/464)亚型/重组亚型.CRF01 AE和CRF BC主要流行于异性性传播、同性性传播和静脉吸毒人群,B'亚型主要经异性、同性性传播和血液传播.另外经系统进化分析发现,不同时间段的样本出现明显的时间汇聚现象,并伴随传播途径的聚集以及交叉感染现象;各亚型/重组株样本组内及与标准参考株间的基因离散率随着时间的增加有明显增大趋势.结论 CRF01 AE重组株是深圳地区HⅣ-1的主要流行株,CRF_BC、B、B'、C、A1和CRF02_AG、CRF06_cpx亚型/重组亚型也在深圳地区少量流行,各亚型在流行过程中发生较大变异.     

A novel multiregion hybridization assay reveals high frequency of dual inter-subtype infections among HIV-positive individuals in Cameroon,West Central Africa

In West and West Central Africa, multiple subtypes, circulating recombinant forms (CRF), and high proportions of unique recombinant forms (URF) are documented. The predominance of recombinants strongly suggests that dual infections occur frequently. In the present study, we adapted the multi-region hybridization assay (MHA), previously developed to identify dual infections in geographic regions where few HIV-1 variants circulate, to identify HIV-1 variants and dual infections.We designed clade-specific probes in three genomic regions (gag p17, vpu, nef) to detect eight different variants that are common in this part of Africa (A, B/D, C, F, G, CRF02_AG, CRF06_cpx, CRF22_01A1). The assay was validated with 163 samples representing the corresponding HIV-1 variants. Depending on the genomic regions, the global sensitivity of the assay ranged from 86% to 94%, and the global specificity was between 85% and 96%. The assay was then applied on 156 antiretroviral treatment-naive patients from Cameroon. The MHA assay identified 79%, 85% and 90% of the strains in nef, gag and vpu regions, respectively. The subtype/CRF distribution and the proportion of inter-region recombinants obtained by the new MHA assay were in accordance with known subtype/CRF distribution in Cameroon. Moreover, the MHA assay identified 35 (22.4%) patients as dually infected, from which 20 were reactive in more than one region and/or with concordant multigenomic recombination pattern.Despite the high genetic diversity, we successfully developed an hybridization assay allowing identification of eight common HIV-1 variants circulating in West and West Central Africa. We documented high rates of dual infection in a low-risk population group, illustrating that the global evolution of HIV diversity is driven by dual infections. This assay could become a useful screening tool for the global surveillance and monitoring of inter-subtype/CRF dual infections in West and West Central Africa.     

Dynamics and molecular evolution of HIV-1 strains in Sicily among antiretroviral naïve patients

HIV-1 subtype B is the most frequent strain in Sicily. To date, there is no available data about the genetic diversity of HIV-1 viral strains circulating in Sicily among antiretroviral (ARV) naïve subjects and the role of immigration as potential determinant of evolutionary dynamics of HIV-1 molecular epidemiology.For this purpose, HIV-1 polymerase (pol) sequences obtained from 155 ARV naïve individuals from 2004 to 2009 were phylogenetically analysed.The overall rate of HIV-1 non-B infections was 31.0% (n = 48/155), increasing from 7.8% in 2004–2006 to 40.9% in 2009, and about one-third were identified as unique recombinant forms.CRF02_AG was the prevalent non-B clade (n = 28/48, 58.3%), while subtype C-related strains were responsible for about 30% HIV-1 infections.Non-B viruses strictly associated with heterosexual transmission (85.4%) and were mostly found among immigrants (77.1%). Phylogenetic analysis of non-B sequences found in foreign-born subjects was geographically correlated to the respective country of origin. Moreover, the detection of non-B viral variants in the autochthonous population may support an increasing genetic diversity in Sicily as well as a local circulation of HIV strains also uncommon in our country.In Sicily, HIV-1 epidemic is still mostly attributable to the B subtype. Nevertheless, migration and population movements are progressively introducing novel HIV-1 subtypes causing a continuous increase of HIV-1 molecular dynamic at local level. Molecular surveillance is needed to monitor the genetic evolution of HIV-1 epidemic.     

High frequency of HIV-1 infections with multiple HIV-1 strains in men having sex with men (MSM) in Senegal

Circulating and unique recombinant HIV-1 strains continue to be identified and their number increases over time, suggesting that co-infection with multiple HIV-1 is frequent. In this study we analyzed to what extent dual infections with different HIV-1 variants occur in a population group with high risk behaviour, high HIV-1 prevalence and in an area where multiple HIV-1 subtypes and Circulating Recombinant Forms (CRFs) co-circulate. We studied 69 MSM with our recently developed multi-region hybridization assay (MHA), based on fluorescent probe detection for eight common variants circulating in West and West Central Africa. At least 11 (15.9%) of the 69 patients were simultaneously infected with two different HIV-1 subtypes and/or CRFs. Among the 29 samples identified as subtype C by MHA in gag, 15 (57.7%) reacted with both C1 and C2 probes. Sequence analysis suggests that the majority of the samples reactive with C1 and C2 probes are most likely infected with two different subtype C clades. Single genome amplification and DNA dilutions confirmed dual infection with subtype D and C for MSM1193, triple infection with two different C subtype strains and one CRF02_AG strain in MSM1157 and showed that MSM3017 is at least co-infected with CRF06_cpx and CRF02_AG and another strain that could not be classified. Comparison of all subtype C sequences from the MSM population and from the general population from this and previous studies confirmed the intermixing of HIV-1 variants between low-risk women and high-risk men as shown by the intermixing of subtype C variants from MSM1157 and a female patient (02SN-HALD478). Comparison of dual infection rates between the general population and MSM in Senegal, show also clearly the importance of high HIV prevalence and high risk behavior in dual infections and subsequent intermixing of HIV-1 variants which can lead to emergence and spread of new recombinants (CRFs).     

Phylogenetics of HIV-1 subtype G env: Greater complexity and older origins than previously reported

HIV-1 subtype G has played an early and central role in the emergent complexity of the HIV-1 group M (HIV-1M) epidemic in central/west Africa. Here, we analysed new subtype G env sequences sampled from 8 individuals in Yaoundé, Cameroon during 2007–2010, together with all publically available subtype G-attributed full-length env sequences with known sampling dates and locations. We inferred that the most recent common ancestor (MRCA) of the analysed subtype G env sequences most likely occurred in ∼1953 (95% Highest Posterior Density interval [HPD] 1939–1963): about 15 years earlier than previous estimates. We found that the subtype G env phylogeny has a complex structure including seven distinct lineages, each likely dating back to the late 1960s or early 1970s. Sequences from Angola, Gabon and the Democratic Republic of Congo failed to group consistently in these lineages, possibly because they are related to more ancient sequences that are poorly sampled. The circulating recombinant form (CRF), CRF06_cpx env sequences but not CRF25_cpx env sequences are phylogenetically nested within the subtype G clade. This confirms that the CRF06_cpx env plausibly was derived through recombination from a subtype G parent, and suggests that the CRF25_cpx env was likely derived from an HIV-1M lineage related to the MRCA of subtype G that has remained undiscovered and may be extinct. Overall, this fills important gaps in our knowledge of the early events in the spread of HIV-1M.     

On the contribution of Angola to the initial spread of HIV-1

Angola borders and has long-term links with Democratic Republic of Congo (DRC) as well as high levels of Human Immunodeficiency Virus (HIV) genetic diversity, indicating a potential role in the initial spread of the HIV-1 pandemic. Herein, we analyze 564 C2V3 and 354 pol publicly available sequences from DRC, Republic of Congo (RC) and Angola to better understand the initial spread of the virus in this region. Phylogeographic analyses were performed with the BEAST software. While our results pinpoint the origin of the pandemic to Kinshasa (DRC) around 1906, the introduction of HIV-1 to Angola could have occurred early between the 1910s and 1940s. Furthermore, most of the HIV-1 migrations out of Kinshasa were directed not only to Lubumbashi and Mbuji-Mayi (DRC), but also to Luanda and Brazzaville. Kinshasa census records corroborate these findings, indicating that the early exportation of the virus to Angola might be related to the high number of Angolans in Kinshasa at that time, originated mostly from the North of Angola.In summary, our results place Angola at the epicenter of the early HIV dissemination, together with DRC and RC.     

Cross-clade immune responses to Gag p24 in patients infected with different HIV-1 subtypes and correlation with HLA class I and II alleles

Individuals infected with different subtypes of HIV-1 (A, B, C, D, CRF01_AE and CRF02_AG) were analyzed for their antigen-specific immune response with respect to their HLA genetics. The p24 Gag protein was selected for analysis, since previous studies of the same cohort of patients had shown that almost 80% of these individuals responded to Gag peptides of subtypes A, B and/or C. A large number of Gag antigen-specific responses were recorded. Both previously recognized as well as new epitopes were identified, assumed to bind HLA classes I and/or II. Fifteen individuals showed class I cellular responses to T cell epitopes irrespective of the infecting virus subtype. For five individuals infected with subtypes A, B, D and CRF02_AG, new T cell epitopes are described. Responses related to the patient's class I alleles are frequent, and several new putative class II responses were found.     

Automated subtyping of HIV-1 genetic sequences for clinical and surveillance purposes: Performance evaluation of the new REGA version 3 and seven other tools

BackgroundTo investigate differences in pathogenesis, diagnosis and resistance pathways between HIV-1 subtypes, an accurate subtyping tool for large datasets is needed. We aimed to evaluate the performance of automated subtyping tools to classify the different subtypes and circulating recombinant forms using pol, the most sequenced region in clinical practice. We also present the upgraded version 3 of the Rega HIV subtyping tool (REGAv3).MethodologyHIV-1 pol sequences (PR + RT) for 4674 patients retrieved from the Portuguese HIV Drug Resistance Database, and 1872 pol sequences trimmed from full-length genomes retrieved from the Los Alamos database were classified with statistical-based tools such as COMET, jpHMM and STAR; similarity-based tools such as NCBI and Stanford; and phylogenetic-based tools such as REGA version 2 (REGAv2), REGAv3, and SCUEAL. The performance of these tools, for pol, and for PR and RT separately, was compared in terms of reproducibility, sensitivity and specificity with respect to the gold standard which was manual phylogenetic analysis of the pol region.ResultsThe sensitivity and specificity for subtypes B and C was more than 96% for seven tools, but was variable for other subtypes such as A, D, F and G. With regard to the most common circulating recombinant forms (CRFs), the sensitivity and specificity for CRF01_AE was ∼99% with statistical-based tools, with phylogenetic-based tools and with Stanford, one of the similarity based tools. CRF02_AG was correctly identified for more than 96% by COMET, REGAv3, Stanford and STAR. All the tools reached a specificity of more than 97% for most of the subtypes and the two main CRFs (CRF01_AE and CRF02_AG). Other CRFs were identified only by COMET, REGAv2, REGAv3, and SCUEAL and with variable sensitivity. When analyzing sequences for PR and RT separately, the performance for PR was generally lower and variable between the tools. Similarity and statistical-based tools were 100% reproducible, but this was lower for phylogenetic-based tools such as REGA (∼99%) and SCUEAL (∼96%).ConclusionsREGAv3 had an improved performance for subtype B and CRF02_AG compared to REGAv2 and is now able to also identify all epidemiologically relevant CRFs. In general the best performing tools, in alphabetical order, were COMET, jpHMM, REGAv3, and SCUEAL when analyzing pure subtypes in the pol region, and COMET and REGAv3 when analyzing most of the CRFs. Based on this study, we recommend to confirm subtyping with 2 well performing tools, and be cautious with the interpretation of short sequences.     

Tracing the origin of a singular HIV-1 CRF45_cpx clade identified in Brazil

The HIV-1 epidemiology has changed over the past decade toward a marked increase in the circulation of strains previously restricted to local epidemics. Recent molecular epidemiological surveys identified some HIV-1 strains of probable African origin circulating in Brazil, including the Circulating Recombinant Form (CRF) 45_cpx, a complex A1/K/U recombinant that circulates in Central Africa. Here, we characterize partial genomic sequences and reconstruct the evolutionary history of HIV-1 CRF45_cpx-related recombinant samples identified in independent studies carried out with HIV + individuals in Brazil. The sequences were obtained by overlapping PCR amplifications followed by direct sequencing. Recombination profiles were determined by phylogenetic and bootscaning analyses. The evolutionary history was estimated by a Bayesian coalescent-based method using datasets representing the gag, pol and env gene fragments. Six of the 10 samples isolated in Rio de Janeiro showed a CRF45_cpx-like pattern throughout the sequenced genome. The remaining were classified as second-generation recombinants, showing the mosaic patterns: CRF45_cpx/B/D/F1/U, CRF45_cpx/B/F1/U, CRF45_cpx/B/U and CRF45_cpx/F1. All Brazilian CRF45_cpx sequences, except one, formed a monophyletic clade (CRF45-BR), which seems to be the result of a single introduction event that has spread to the Rio de Janeiro, São Paulo and Minas Gerais states and is related to sequences from Argentina, Italy and Belgium. The Bayesian analyses pointed out quite consistent onset dates for CRF45-BR clade (~ 1984: 1976–1996) in the three gene datasets. These results indicate that the CRF45-BR clade has been circulating in the Southeastern Brazilian region for about 30 years, although its presence was not detected until recently due to its very low prevalence. This reinforces the relevance of large-scale molecular surveillance data to identify the emergence of new HIV variants and their impact on local epidemics.     

Reconstituting the epidemic history of mono lineage of HIV-1 CRF01_AE in Guizhou province,Southern China

Guizhou province, located between border provinces and Central province of China, plays a crucial role in the transmission of HIV-1, implying it is important to monitor the epidemic of HIV-1 in this region. Available HIV-1 infected patients’ plasma (n = 78) were collected from Tongren city, Eastern Guizhou. Full-length gag, partial pol and env gene sequences were amplified and analyzed using phylogenetic, recombinant and Bayesian molecular clock approaches. Phylogenetic and recombinant analyses showed that CRF01_AE predominated among injecting drug users and heterosexuals in Tongren city with 85.9% proportion, it was followed by B′ (5.1%), CRF07_BC (3.8%), CRF08_BC (3.8%), and B (1.3%). Moreover, 98.5% of CRF01_AE strains belonged to the distinct lineage CRF01_AE-v previously found in Guangxi province. To infer the most probable origin of CRF01_AE-v in Guizhou province, we download all available full length of CRF01_AE gag, pol and env gene region sequences from China in Los Alamos HIV sequence database. Phylodynamic and phylogeographic analyses revealed that the expanding CRF01_AE-v epidemic in Guizhou province was the result of local epidemic driven by multiple independent introductions of CRF01_AE-v strains from Guangxi province in early 2000s. High prevalence of CRF01_AE in Guizhou province may bridge the epidemic to Central China. It provides a new insight for the understanding of HIV-1 epidemic in Guizhou province and makes the evolutionary history of CRF01_AE in China more intact.     

不同途径感染人群HIV-1亚型分布

目的 了解河北省石家庄市不同感染人群人类免疫缺陷病毒Ⅰ型(HIV-1)亚型及分布特点.方法 从石家庄市报告的148例HIV-1抗体阳性者抗凝全血中提取前病毒DNA,用套式聚合酶链反应(nested-PER)扩增病毒膜蛋白(ENV)基因的C2-V3区并进行序列测定,与国际标准参考序列比较确定亚型.结果 148例样品分属8个亚型,45例为欧美B,37例为CRF07-BC,35例为泰国B(B'),25例为CRF01-AE,C和CRF02-AG各2例,CRF03-AB和CRF11-CPX各1例.结论 既往供受血人员和注射吸毒人群感染的HIV-1亚型相对单一,性传播亚型分布较广.     

Emergence of Vaccine-derived Polioviruses,Democratic Republic of Congo, 2004–2011

Polioviruses isolated from 70 acute flaccid paralysis patients from the Democratic Republic of Congo (DRC) during 2004–2011 were characterized and found to be vaccine-derived type 2 polioviruses (VDPV2s). Partial genomic sequencing of the isolates revealed nucleotide sequence divergence of up to 3.5% in the viral protein 1 capsid region of the viral genome relative to the Sabin vaccine strain. Genetic analysis identified at least 7 circulating lineages localized to specific geographic regions. Multiple independent events of VDPV2 emergence occurred throughout DRC during this 7-year period. During 2010–2011, VDPV2 circulation in eastern DRC occurred in an area distinct from that of wild poliovirus circulation, whereas VDPV2 circulation in the southwestern part of DRC (in Kasai Occidental) occurred within the larger region of wild poliovirus circulation.