scholarly journals Nation-Wide Viral Sequence Analysis of HIV-1 Subtype B Epidemic in 2003–2012 Revealed a Contribution of Men Who Have Sex With Men to the Transmission Cluster Formation and Growth in Japan

2020 ◽  
Vol 2 ◽  
Author(s):  
Teiichiro Shiino ◽  
Atsuko Hachiya ◽  
Junko Hattori ◽  
Wataru Sugiura ◽  
Kazuhisa Yoshimura

Background: To better understand the epidemiology of human immunodeficiency virus type 1 (HIV-1) subtype B transmission in Japan, phylodynamic analysis of viral pol sequences was conducted on individuals newly diagnosed as HIV-1 seropositive.Methodology: A total of 5,018 patients newly diagnosed with HIV-1 infection and registered in the Japanese Drug Resistance HIV Surveillance Network from 2003 to 2012 were enrolled in the analysis. Using the protease-reverse transcriptase nucleotide sequences, their subtypes were determined, and phylogenetic relationships among subtype B sequences were inferred using three different methods: distance-matrix, maximum likelihood, and Bayesian Markov chain Monte Carlo. Domestically spread transmission clusters (dTCs) were identified based on the following criteria: >95% in interior branch test, >95% in Bayesian posterior probability and <10% in depth-first searches for sub-tree partitions. The association between dTC affiliation and individuals' demographics was analyzed using univariate and multivariate analyses.Results: Among the cases enrolled in the analysis, 4,398 (87.6%) were classified as subtype B. Many of them were Japanese men who had sex with men (MSM), and 3,708 (84.3%) belonged to any of 312 dTCs. Among these dTCs, 243 (77.9%) were small clusters with <10 individuals, and the largest cluster consisted of 256 individuals. Most dTCs had median time of the most recent common ancestor between 1995 and 2005, suggesting that subtype B infection was spread among MSMs in the second half of the 1990s. Interestingly, many dTCs occurred within geographical regions. Comparing with singleton cases, TCs included more MSM, young person, and individuals with high CD4+ T-cell count at the first consultation. Furthermore, dTC size was significantly correlated with gender, age, transmission risks, recent diagnosis and relative population size of the region mainly distributed.Conclusions: Our study clarified that major key population of HIV-1 subtype B epidemic in Japan is local MSM groups. The study suggests that HIV-1 subtype B spread via episodic introductions into the local MSM groups, some of the viruses spread to multiple regions. Many cases in dTC were diagnosed during the early phase of infection, suggesting their awareness to HIV risks.

2021 ◽  
Author(s):  
Joan Bacque ◽  
Elena Delgado ◽  
Sonia Benito ◽  
Maria Moreno-Lorenzo ◽  
Vanessa Montero ◽  
...  

Circulating recombinant forms (CRFs) are important components of the HIV-1 pandemic. Among 108 reported in the literature, 17 are BF1 intersubtype recombinant, most of which are of South American origin. Among these, all 5 identified in the Southern Cone and neighboring countries, except Brazil, derive from a common recombinant ancestor related to CRF12_BF, which circulates widely in Argentina, as deduced from coincident breakpoints and clustering in phylogenetic trees. In a HIV-1 molecular epidemiological study in Spain, we identified a phylogenetic cluster of 20 samples from 3 separate regions which were of F1 subsubtype, related to the Brazilian strain, in protease-reverse transcriptase (Pr-RT) and of subtype B in integrase. Remarkably, 14 individuals from this cluster (designated BF9) were Paraguayans and only 4 were native Spaniards. HIV-1 transmission was predominantly heterosexual, except for a subcluster of 6 individuals, 5 of which were men who have sex with men. Ten additional database sequences, from Argentina (n=4), Spain (n=3), Paraguay (n=1), Brazil (n=1), and Italy (n=1), branched within the BF9 cluster. To determine whether it represents a new CRF, near full-length genome (NFLG) sequences were obtained for 6 viruses from 3 Spanish regions. Bootscan analyses showed a coincident BF1 recombinant structure, with 5 breakpoints, located in p17gag, integrase, gp120, gp41-rev overlap, and nef, which was identical to that of two BF1 recombinant viruses from Paraguay previously sequenced in NFLGs. Interestingly, none of the breakpoints coincided with those of CRF12_BF. In a maximum likelihood phylogenetic tree, all 8 NFLG sequences grouped in a strongly supported clade segregating from previously identified CRFs and from the CRF12_BF family clade. These results allow us to identify a new HIV-1 CRF, designated CRF66_BF. Through a Bayesian coalescent analysis, the most recent common ancestor of CRF66_BF was estimated around 1984 in South America, either in Paraguay or Argentina. Among Pr-RT sequences obtained by us from HIV-1-infected Paraguayans living in Spain, 14 (20.9%) of 67 were of CRF66_BF, suggesting that CRF66_BF may be one of the major HIV-1 genetic forms circulating in Paraguay. CRF66_BF is the first reported non-Brazilian South American HIV-1 CRF_BF unrelated to CRF12_BF


2021 ◽  
Vol 12 ◽  
Author(s):  
Joan Bacqué ◽  
Elena Delgado ◽  
Sonia Benito ◽  
María Moreno-Lorenzo ◽  
Vanessa Montero ◽  
...  

Circulating recombinant forms (CRFs) are important components of the HIV-1 pandemic. Among 110 reported in the literature, 17 are BF1 intersubtype recombinant, most of which are of South American origin. Among these, all 5 identified in the Southern Cone and neighboring countries, except Brazil, derive from a common recombinant ancestor related to CRF12_BF, which circulates widely in Argentina, as deduced from coincident breakpoints and clustering in phylogenetic trees. In a HIV-1 molecular epidemiological study in Spain, we identified a phylogenetic cluster of 20 samples from 3 separate regions which were of F1 subsubtype, related to the Brazilian strain, in protease-reverse transcriptase (Pr-RT) and of subtype B in integrase. Remarkably, 14 individuals from this cluster (designated BF9) were Paraguayans and only 4 were native Spaniards. HIV-1 transmission was predominantly heterosexual, except for a subcluster of 6 individuals, 5 of which were men who have sex with men. Ten additional database sequences, from Argentina (n = 4), Spain (n = 3), Paraguay (n = 1), Brazil (n = 1), and Italy (n = 1), branched within the BF9 cluster. To determine whether it represents a new CRF, near full-length genome (NFLG) sequences were obtained for 6 viruses from 3 Spanish regions. Bootscan analyses showed a coincident BF1 recombinant structure, with 5 breakpoints, located in p17gag, integrase, gp120, gp41-rev overlap, and nef, which was identical to that of two BF1 recombinant viruses from Paraguay previously sequenced in NFLGs. Interestingly, none of the breakpoints coincided with those of CRF12_BF. In a maximum likelihood phylogenetic tree, all 8 NFLG sequences grouped in a strongly supported clade segregating from previously identified CRFs and from the CRF12_BF “family” clade. These results allow us to identify a new HIV-1 CRF, designated CRF66_BF. Through a Bayesian coalescent analysis, the most recent common ancestor of CRF66_BF was estimated around 1984 in South America, either in Paraguay or Argentina. Among Pr-RT sequences obtained by us from HIV-1-infected Paraguayans living in Spain, 14 (20.9%) of 67 were of CRF66_BF, suggesting that CRF66_BF may be one of the major HIV-1 genetic forms circulating in Paraguay. CRF66_BF is the first reported non-Brazilian South American HIV-1 CRF_BF unrelated to CRF12_BF.


Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 93
Author(s):  
Javier E. Cañada ◽  
Elena Delgado ◽  
Horacio Gil ◽  
Mónica Sánchez ◽  
Sonia Benito ◽  
...  

The extraordinary genetic variability of human immunodeficiency virus type 1 (HIV-1) group M has led to the identification of 10 subtypes, 102 circulating recombinant forms (CRFs) and numerous unique recombinant forms. Among CRFs, 11 derived from subtypes B and C have been identified in China, Brazil, and Italy. Here we identify a new HIV-1 CRF_BC in Northern Spain. Originally, a phylogenetic cluster of 15 viruses of subtype C in protease-reverse transcriptase was identified in an HIV-1 molecular surveillance study in Spain, most of them from individuals from the Basque Country and heterosexually transmitted. Analyses of near full-length genome sequences from six viruses from three cities revealed that they were BC recombinant with coincident mosaic structures different from known CRFs. This allowed the definition of a new HIV-1 CRF designated CRF108_BC, whose genome is predominantly of subtype C, with four short subtype B fragments. Phylogenetic analyses with database sequences supported a Brazilian ancestry of the parental subtype C strain. Coalescent Bayesian analyses estimated the most recent common ancestor of CRF108_BC in the city of Vitoria, Basque Country, around 2000. CRF108_BC is the first CRF_BC identified in Spain and the second in Europe, after CRF60_BC, both phylogenetically related to Brazilian subtype C strains.


2015 ◽  
Vol 90 (3) ◽  
pp. 1244-1258 ◽  
Author(s):  
Natalie N. Kinloch ◽  
Daniel R. MacMillan ◽  
Anh Q. Le ◽  
Laura A. Cotton ◽  
David R. Bangsberg ◽  
...  

ABSTRACTHuman leukocyte antigen (HLA) class I-associated polymorphisms in HIV-1 that persist upon transmission to HLA-mismatched hosts may spread in the population as the epidemic progresses. Transmission of HIV-1 sequences containing such adaptations may undermine cellular immune responses to the incoming virus in future hosts. Building upon previous work, we investigated the extent of HLA-associated polymorphism accumulation in HIV-1 polymerase (Pol) through comparative analysis of linked HIV-1/HLA class I genotypes sampled during historic (1979 to 1989;n= 338) and modern (2001 to 2011;n= 278) eras from across North America (Vancouver, BC, Canada; Boston, MA; New York, NY; and San Francisco, CA). Phylogenies inferred from historic and modern HIV-1 Pol sequences were star-like in shape, with an inferred most recent common ancestor (epidemic founder virus) sequence nearly identical to the modern North American subtype B consensus sequence. Nevertheless, modern HIV-1 Pol sequences exhibited roughly 2-fold-higher patristic (tip-to-tip) genetic distances than historic sequences, with HLA pressures likely driving ongoing diversification. Moreover, the frequencies of published HLA-associated polymorphisms in individuals lacking the selecting HLA class I allele was on average ∼2.5-fold higher in the modern than in the historic era, supporting their spread in circulation, though some remained stable in frequency during this time. Notably, polymorphisms restricted by protective HLA alleles appear to be spreading to a greater relative extent than others, though these increases are generally of modest absolute magnitude. However, despite evidence of polymorphism spread, North American hosts generally remain at relatively low risk of acquiring an HIV-1 polymerase sequence substantially preadapted to their HLA profiles, even in the present era.IMPORTANCEHLA class I-restricted cytotoxic T-lymphocyte (CTL) escape mutations in HIV-1 that persist upon transmission may accumulate in circulation over time, potentially undermining host antiviral immunity to the transmitted viral strain. We studied >600 experimentally collected HIV-1 polymerase sequences linked to host HLA information dating back to 1979, along with phylogenetically reconstructed HIV-1 sequences dating back to the virus' introduction into North America. Overall, our results support the gradual spread of many—though not all—HIV-1 polymerase immune escape mutations in circulation over time. This is consistent with recent observations from other global regions, though the extent of polymorphism accumulation in North America appears to be lower than in populations with high seroprevalence, older epidemics, and/or limited HLA diversity. Importantly, the risk of acquiring an HIV-1 polymerase sequence at transmission that is substantially preadapted to one's HLA profile remains relatively low in North America, even in the present era.


2022 ◽  
Vol 12 ◽  
Author(s):  
Bin Zhao ◽  
Wei Song ◽  
Mingming Kang ◽  
Xue Dong ◽  
Xin Li ◽  
...  

Since the implementation of the “treat all” policy in China in 2016, there have been few data on the prevalence of transmitted drug resistance (TDR) in China. In this study, we describe TDR in patients newly diagnosed with human immunodeficiency virus (HIV) infection between 2016 and 2019 in Shenyang city, China. Demographic information and plasma samples from all newly reported HIV-infected individuals in Shenyang from 2016 to 2019 were collected. The HIV pol gene was amplified and sequenced for subtyping and TDR. The spread of TDR was analyzed by inferring an HIV molecular network based on pairwise genetic distance. In total, 2,882 sequences including CRF01_AE (2019/2,882, 70.0%), CRF07_BC (526/2,882, 18.3%), subtype B (132/2,882, 4.6%), and other subtypes (205/2,882, 7.1%) were obtained. The overall prevalence of TDR was 9.1% [95% confidence interval (CI): 8.1–10.2%]; the prevalence of TDR in each subtype in descending order was CRF07_BC [14.6% (95% CI: 11.7–18.0%)], subtype B [9.1% (95% CI: 4.8–15.3%)], CRF01_AE [7.9% (95% CI: 6.7–9.1%)], and other sequences [7.3% (95% CI: 4.2–11.8%)]. TDR mutations detected in more than 10 cases were Q58E (n = 51), M46ILV (n = 46), K103N (n = 26), E138AGKQ (n = 25), K103R/V179D (n = 20), and A98G (n = 12). Molecular network analysis revealed three CRF07_BC clusters with TDR [two with Q58E (29/29) and one with K103N (10/19)]; and five CRF01_AE clusters with TDR [two with M46L (6/6), one with A98G (4/4), one with E138A (3/3), and one with K103R/V179D (3/3)]. In the TDR clusters, 96.4% (53/55) of individuals were men who have sex with men (MSM). These results indicate that TDR is moderately prevalent in Shenyang (5–15%) and that TDR strains are mainly transmitted among MSM, providing precise targets for interventions in China.


2021 ◽  
Vol 17 (2) ◽  
pp. e1009258
Author(s):  
Yang Gao ◽  
Shan He ◽  
Wen Tian ◽  
Dan Li ◽  
Minghui An ◽  
...  

Human immunodeficiency virus type 1 (HIV-1) recombinants in the world are believed to be generated through recombination between distinct HIV-1 strains among coinfection or superinfection cases. However, direct evidence to support transmission of HIV-1 recombinants from a coinfected/superinfected donor to putative recipient is lacking. Here, we report on the origin and evolutionary relationship between a set of recombinants from a CRF01_AE/CRF07_BC superinfected putative donor and diverse CRF01_AE/CRF07_BC recombinants from five putative recipients. Interviews on sociodemographic characteristics and sexual behaviors for these six HIV-1-infected men who have sex with men showed that they had similar ways of partner seeking: online dating sites and social circles. Phylogenetic and recombination analyses demonstrated that the near-full-length genome sequences from six patients formed a monophyletic cluster different from known HIV-1 genotypes in maximum likelihood phylogenetic trees, were all composed of CRF01_AE and CRF07_BC fragments with two common breakpoints on env, and shared 4–7 breakpoints with each other. Moreover, 3’ half-genomes of recombinant strains from five recipients had identical/similar recombinant structures with strains at longitudinal samples from the superinfected donor. Recombinants from the donor were paraphyletic, whereas five recipients were monophyletic or polyphyletic in the maximum clade credibility tree. Bayesian analyses confirmed that the estimated time to the most recent common ancestor (tMRCA) of CRF01_AE and CRF07_BC strains of the donor was 2009.2 and 2010.7, respectively, and all were earlier than the emergence of recombinants from five recipients. Our results demonstrated that the closely related unique recombinant forms of HIV-1 might be the descendent of a series of recombinants generated gradually in a superinfected patient. This finding highlights the importance of early initiation of antiretroviral therapy as well as tracing and testing of partners in patients with multiple HIV-1 infection.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Jiafeng Zhang ◽  
Qin Fan ◽  
Mingyu Luo ◽  
Jiaming Yao ◽  
Xiaohong Pan ◽  
...  

Abstract Background In China, an HIV-infected man (complainant; P2) alleged that another man (defendant; P1) had unlawfully infected him with HIV through unprotected homosexual contact in 2018. Methods We employed epidemiological, serological and phylogenetic analyses to investigate the transmission linkage between two men who have sex with men (MSM). Partial segments of three HIV-1 gene regions (gag, pol, and env) were amplified and sequenced by cloning. Maximum-likelihood (ML) and Bayesian methods were used to determine the direction and estimate the timing of transmission. Local control sequences and database control sequences were also used in the phylogenetic analysis. Results It indicated that P2 underwent HIV seroconversion after P1 was diagnosed as HIV positive. The time to the most recent common ancestor (tMRCA) estimates consistently showed that P1 most likely became HIV-1 infected at an earlier date than P2. P1 and P2 were infected with the same HIV-1 CRF01_AE subtype according to segments of all three gene regions (gag, pol, and env). All three genetic regions of P1 have been subject to more potential selective forces than those of P2, indicating a longer evolutionary history. Bayesian and ML trees showed similar paraphyletic-monophyletic topologies of gag and env, with the virus from P1 located at the root, which supported a P1-to-P2 transmission direction. Conclusions Phylogenetic investigations can elucidate HIV transmission linkage and might empower its use in the opposition of the intentional transmission of HIV-1 as a forensic tool.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhen Wang ◽  
Bin Zhao ◽  
Minghui An ◽  
Wei Song ◽  
Xue Dong ◽  
...  

Abstract Background To assess transmitted drug resistance (TDR) to tenofovir (TDF)/emtricitabine (FTC), using as pre-exposure prophylaxis, among newly diagnosed human immunodeficiency virus-1 (HIV-1)-infected residents in Shenyang city, northeast China. Methods Demographic and epidemiological information of all newly diagnosed HIV-1 infected residents in Shenyang city from 2016 to 2018 were anonymously collected from the local HIV epidemic database. HIV-1 pol sequences were amplified from RNA in cryopreserved plasma samples and sequenced directly. Viral subtypes were inferred with phylogenetic analysis and drug resistance mutations (DRMs) were determined according to the Stanford HIVdb algorithm. Recent HIV infection was determined with HIV Limiting Antigen avidity electro immunoassay. Results A total of 2176 sequences (92.4%, 2176/2354) were obtained; 70.9% (1536/2167) were CRF01_AE, followed by CRF07_BC (18.0%, 391/2167), subtype B (4.7%, 102/2167), other subtypes (2.6%, 56/2167), and unique recombinant forms (3.8%, 82/2167). The prevalence of TDR was 4.9% (107/2167), among which, only 0.6% (13/2167) was resistance to TDF/FTC. Most of these subjects had CRF01_AE strains (76.9%, 10/13), were unmarried (76.9%, 10/13), infected through homosexual contact (92.3%, 12/13), and over 30 years old (median age: 33). The TDF/FTC DRMs included K65R (8/13), M184I/V (5/13), and Y115F (2/13). Recent HIV infection accounted for only 23.1% (3/13). Most cases were sporadic in the phylogenetic tree, except two CRF01_AE sequences with K65R (Bootstrap value: 99%). Conclusions The prevalence of TDR to TDF/FTC is low among newly diagnosed HIV-infected cases in Shenyang, suggesting that TDR may have little impact on the protective effect of the ongoing CROPrEP project in Shenyang city.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shingo Nishiki ◽  
Kenichi Lee ◽  
Mizue Kanai ◽  
Shu-ichi Nakayama ◽  
Makoto Ohnishi

AbstractJapan has had a substantial increase in syphilis cases since 2013. However, research on the genomic features of the Treponema pallidum subspecies pallidum (TPA) strains from these cases has been limited. Here, we elucidated the genetic variations and relationships between TPA strains in Japan (detected between 2014 and 2018) and other countries by whole-genome sequencing and phylogenetic analyses, including syphilis epidemiological surveillance data and information on patient sexual orientation. Seventeen of the 20 strains in Japan were SS14- and the remaining 3 were Nichols-lineage. Sixteen of the 17 SS14-lineage strains were classified into previously reported Sub-lineage 1B. Sub-lineage 1B strains in Japan have formed distinct sub-clusters of strains from heterosexuals and strains from men who have sex with men. These strains were closely related to reported TPA strains in China, forming an East-Asian cluster. However, those strains in these countries evolved independently after diverging from their most recent common ancestor and expanded their genetic diversity during the time of syphilis outbreak in each country. The genetic difference between the TPA strains in these countries was characterized by single-nucleotide-polymorphism analyses of their penicillin binding protein genes. Taken together, our results elucidated the detailed phylogenetic features and transmission networks of syphilis.


2014 ◽  
Vol 143 (3) ◽  
pp. 663-672 ◽  
Author(s):  
J. HUA ◽  
H. LIN ◽  
Y. DING ◽  
D. QIU ◽  
F. WONG ◽  
...  

SUMMARYLittle is known about HIV drug resistance (HIVDR) in newly diagnosed HIV-infected adults in eastern China where the HIV epidemic is spreading predominantly through sexual contact. During 2008–2011, newly HIV-diagnosed adults in Taizhou prefecture, Zhejiang province in eastern China were examined for HIVDR by amplifying and sequencing the HIV-1 pol gene. Of 447 genotyped participants, 53·7% were infected with CRF01_AE, 20·1% with CRF07_BC, 12·5% with subtype B, and 11·6% with CRF08_BC. Most of the participants had one or more minor genetic mutations in the pol gene that are associated with HIVDR. Twelve (2·7%) participants met the standard guidelines of having low to high HIVDR, suggesting that the prevalence of HIVDR in newly HIV-diagnosed adults was low in the study area and current antiretroviral therapy (ART) regimens are likely to remain effective. However, given high frequency of minor HIVDR in HIV patients and the scaling up of ART programmes in China, larger HIVDR surveillance programmes are needed.


Sign in / Sign up

Export Citation Format

Share Document