AE Backbone Research Articles

Characterization of Two Novel HIV-1 CRF01_AE/CRF07_BC Recombinant Forms Among Men Who Have Sex with Men and Mother-to-Child Transmission Cases in Baoding City, China.

CRF01_AE and CRF07_BC are predominant circulating HIV-1 subtypes in China. In this study, we report two novel HIV-1 CRF01_AE/CRF07_BC recombinant forms isolated from one man who has sex with men (MSM) (BDD027) and one mother-to-child transmission (MTCT) case (BDL123) in Baoding City, Hebei Province, China. The recombination breakpoint analysis showed that the recombination pattern of the near-full-length genome of BDD027 consisted of two CRF07_BC fragments inserted into a CRF01_AE backbone, while the recombination pattern of the near-full-length genome of BDL123 consisted of one CRF01_AE fragment inserted into a CRF07_BC backbone. This study demonstrates the importance of strengthening the monitoring of HIV-1 molecular epidemiological characteristics and emphasizes the urgent need to reduce the HIV-1 epidemic among MSM and MTCT populations in China.

Identification of Two HIV-1 CRF01_AE/B Recombinant Forms and a CRF01_AE/B/C Recombinant Form in Hebei Province, China.

In the Hebei province, Human Immunodeficiency Virus type one (HIV-1) recombinant strains of subtypes B, C, and CRF01_AE are emerging very rapidly and diversely. In order to confirm the characteristics of novel recombination forms, we aimed to analyze HIV-1 Near-full-length Genome sequences (NFLGs) obtained from three Men who have Sex with Men (MSM) in this study. Phylogenetic trees were constructed and breakpoints analysis was performed based on the NFLGs and each gene fragment to examine the gene recombination patterns of three new HIV-1 NFLGs. HIV-1 subtypes CRF01_AE and B were combined to generate the recombinant structures of the NFLGs 610 and 687. CRF01_AE, B, and C were combined to generate the recombinant structures of the NFLG 825. According to the NFLG phylogenetic tree, the NFLG 825 clustered with CRF65_cpx and the NFLGs 610 and 687 clustered with CRF68_01B. The recombination breakpoints analysis revealed that the recombination pattern of the NFLGs 610 and 687 was the insertion of subtype B fragment into the CRF01_AE backbone. Subregions I, II, and III were derived from CRF01_AE, subtype B, and CRF01_AE, respectively. The recombination pattern of the NFLG 825 contained ten fragments of subtypes CRF01_AE, C, and B. Finally, the above factors were formed using phylogenetic trees and breakpoints analysis, which were combined to get two CRF68_01B forms and one CRF65_cpx form. Our findings have suggested that it is crucial to keep an eye on the genetic diversity of HIV-1 in Hebei province.

Three Novel CRF01_AE/CRF07_BC Recombinant Forms of HIV-1 Identified in Shijiazhuang City, China.

Hebei, a province with a low Human Immunodeficiency Virus (HIV) prevalence, is also a region with the most abundant HIV-1 genetic diversity. HIV-1 recombinant forms have been the key factor influencing the effectiveness of HIV-1 control and therapy. We aimed to study inter-subtype recombinant structures of new HIV-1-second generation recombinant forms. Monitoring the HIV-1 subtype by phylogenetic and recombinant breakpoint analyses are the two most frequent methods among men who have sex with men (MSM). Here, three near full-length genomes (NFLGs) were obtained from HIV-1 seropositive MSM in Shijiazhuang City, China, who have never received antiretroviral therapy in 2021. Phylogenetic analysis indicated that three NFLGs were novel inter-subtype recombinant forms between CRF07_BC and CRF01_AE. For the NFLG 21S009, four CRF07_BC gene fragments were inserted into the pol, vif-vpr, vpu-env, and nef-3` LTR gene regions within a CRF01_ AE backbone, respectively. For the NFLG 21S095, four breakpoints were identified in HIV-1 pol and vpu regions. The NFLG 21S370 contained four gene recombinant breakpoints within HIV-1 pol and vpu-env gene regions. Of these three NFLGs, the NFLG 21S009 contained the most breakpoints, distributed in the pol, vif, vpr, vpu, env, and nef regions, respectively. In the gag-pol regions, three NFLGs had only one CRF07_BC gene fragment inserted into gene points between 4250 and 4792. Our findings provide strong evidence that the surveillance of novel recombinant forms is necessary for the increase in better control of HIV.

Identification of Two Novel HIV-1 Second-Generation Recombinant Forms (CRF01_AE/CRF07_BC) in Men Who Have Sex with Men in Hebei, China.

In recent years, men who have sex with men (MSM) have been identified as the primary source of HIV-1 transmission in Hebei Province, China. Co-circulation of multiple subtypes in HIV-1 positive MSM populations may contribute to the emergence of the second generation of recombinant HIV-1 strains, indicating the occurrence of dual infections or superinfections in MSM populations. Thus, the discovery of new recombinant strains is important to indicate the appearance of multiple infected individuals and the prevalence caused by changes in the parent strains. In this study, we present two new unique recombinant forms (URFs) from two HIV-1-positive subjects (HB070052 and HB070056) infected through homosexual contact in Hebei Province, China. The near full-length genome of the two URFs revealed that HB070052 was divided into seven segments by six breakpoints in the gag, pol, vif, and vpr genes; HB070056 was separated into five fragments by four breakpoints, with two regions of CRF07_BC inserted into a CRF01_AE backbone's gag, pol regions. The subregion tree showed CRF01_AE segments were traced back to the cluster 4 and 6 of the CRF01_AE phylogenetic tree, which were prevalent among HIV-1 infections through MSM in China. The continued emergence of the novel CRF01_AE/CRF07_BC recombinant forms indicates the HIV-1 epidemic is complex and long-term surveillance of recombinant strains is necessary among MSM in this region.

Genomic Characterization of a Novel HIV-1 Second-Generation Recombinant (CRF01_AE/CRF07_BC) Identified from an MSM Patient in Hebei, China.

Along with the co-circulation of dominant HIV-1 strains (CRF01_AE and CRF07_BC) in China, an increasing number of second-generation recombinants are being detected, especially among men who have sex with men (MSM). Here, we identified a unique CRF01_AE/CRF07_BC recombinant from a HIV-1-positive man (BDD015A) infected through homosexual transmission in Baoding city, Hebei Province. Analysis of the near full-length genome sequence of the recombinant revealed five segments divided by four breakpoints, with two regions of CRF07_BC inserted into the pol and env regions of the CRF01_AE backbone. Three CRF01_AE segments (I, III, and V) clustered within the cluster 4 lineage, which mainly circulated among MSM in China. This recombinant differed from previously reported CRF01_ AE and CRF07_BC recombinant forms. The continuous emergence of novel recombinants increases the genetic complexity of HIV-1 in Hebei. Further measures are needed to monitor the molecular epidemiological characteristics of HIV-1 to help control the spread of infections.

Near-full-length genomic characteristics of three novel HIV-1 CRF01_AE/C recombinant forms among men who have sex with men in Hebei province, China.

Subtypes circulating recombinant form (CRF) 01_AE and C are two Human immunodeficiency viru (HIV)-1 strains that are prevalent in different key populations such as men who have sex with men (MSM) in China. Co-circulating of different HIV-1 subtypes is easy to result in the generation of second-generation recombinants. In this study, three new HIV-1 CRF01_AE/C recombinants from three MSMs were detected in Hebei province, China. Phylogenetic tree and recombination analysis showed that the near-full-length genomic (NFLG) of S114 had seven recombination breakpoints, including four C fragments inserted into the CRF01_AE backbone; M363 had six recombination breakpoints, including three C fragments inserted into the CRF01_AE backbone; M162 had eight recombination breakpoints, including four C fragments inserted into the CRF01_AE backbone. Furthermore, Phylogenetic tree analysis based on subregion gene fragments also identified this kind of CRF01_AE/C recombinant structure. This study suggests a more complex HIV-1 epidemiological trend in Hebei province, China and the urgency of continuous HIV-1 recombinant strain registry in sexually transmitted populations.

Recombinant characteristics of three novel HIV-1 second-generation recombinant forms composed of CRF01_AE and CRF07_BC isolated in Hebei province, China

Human immunodeficiency virus 1 (HIV-1) is a fast-evolving, genetically diverse virus. The HIV-1 evolution rate is also significantly influenced by the frequency of HIV-1 spread in a population. Transmission via homosexual contact has become the predominant transmission route, leading to an increase in the HIV-1 epidemic in Hebei province, China. In this study, we report three novel HIV-1 CRF01_AE/CRF07_BC recombinant forms isolated from three men who have sex with men (MSM) in the cities of Shijiazhuang (20747) and Langfang (20809 and 20820). Phylogenetic analysis based on HIV-1 near-full-length genome (NFLG) sequences indicated that the three novel recombinant forms formed a distinct monophyletic branch that was separate from all known HIV-1 subtypes and circulating recombinant forms (CRFs). Breakpoint analysis showed that the three NFLGs displayed different recombinant patterns. NFLGs 20747 and 20809 had a recombinant pattern with subtype CRF01_AE gene fragments inserted into a CRF07_BC backbone, spanning from the gag to env gene regions, whereas NFLG 20820 had a recombinant pattern with subtype CRF07_BC gene fragments inserted into a CRF01_AE backbone. Subregion phylogenetic analysis confirmed that these three NFLGs comprised CRF01_AE and CRF07_BC. Our findings confirm the emergence of novel recombinant forms and highlight the need for continuous monitoring of the diversity of HIV-1 among sexually active populations, especially MSM, to better control the HIV-1 epidemic.

Identification of two novel HIV-1 recombinant forms originated from CRF01_AE and subtype B in the sexual contact population in Hebei province, China.

Two near full-length genome (NFLG) sequences of HIV-1 with undefined subtypes were analyzed to confirm the recombinant characteristics. In order to analyze the gene recombination patterns and breakpoints of these two NFLGs, the phylogenetic trees based on the NFLG sequences and their subregions were constructed, respectively. Sequences 233 and 953 are novel second-generation recombinant forms of HIV-1 CRF01_AE and subtype B. The NFLG phylogenetic tree analysis showed that these two NFLG sequences formed a unique monophyletic branch, respectively. The recombination breakpoints analysis showed that the recombination pattern of both sequences was that a subtype B fragment was inserted into a CRF01_AE backbone. Subregions I, II and III were from CRF01_AE, subtype B and CRF01_AE, respectively. The recombination breakpoints relative to HXB2 of sequences 233 and 953 were 2400 and 4870, and 3363 and 4828, respectively. The emergence of novel recombinant forms of CRF01_AE/B demonstrates that we should carry out the ongoing surveillance of HIV-1 recombinant forms in sexually transmitted population.

Identification of two novel HIV-1 circulating recombinant forms of CRF111_01C and CRF116_0108 in southwestern Yunnan, China

ABSTRACT Yunnan, the region hardest hit by HIV/AIDS in China, is also an area with the most abundant HIV-1 genetic diversity. A large number of novel HIV-1 circulating recombinant forms (CRFs) and unique recombinants were identified among injection drug users in Yunnan; however, few were found among sexual contacts. Here, we obtained 15 near full-length genome sequences (NFLGs) from HIV-1 seropositive heterosexual contacts in Yunnan who received antiretroviral therapy during the period from 2014 to 2016. Phylogenetic analysis showed that six NFLGs belonged to CRF01_AE (n = 3) and CRF106_cpx (n = 3), and the other nine sequences were novel inter-subtype recombinants. Of the recombinants, two novel CRFs (CRF111_01 C (n = 4) and CRF116_0108 (n = 4)) and one CRF106_cpx variant (n = 1) were identified. CRF111_01 C had a CRF01_AE backbone with seven subtype C fragments inserted into the gag, pol, vif, env, nef and 3ʹLTR regions. CRF116_0108 had a CRF08_BC backbone with a CRF01_AE fragment inserted into the pol, tat, rev, vif, vpr, vpu and env regions. Phylogeographic analyses estimated that CRF111_01 C and CRF116_0108 originated approximately 1995.7–1998.6 and 1991.7–1993.7, respectively. These identifications of two novel HIV-1 CRFs highlighted the importance of continuous surveillance in heterosexual contacts and other high-risk groups in this region and the surrounding regions.

Identification of a newly emerging HIV-1 CRF111_01C comprising CRF01_AE and C in Yunnan, China: Genetic characterization and recombinant history.

New human immunodeficiency virus (HIV)-1 circulating recombinant forms (CRFs) have recently emerged and disseminated rapidly in China; in total 38 CRFs have been identified thus far. Yunnan province shares its border with Myanmar, and is regarded as a "hotspot" for the occurrence of new HIV-1 recombinations; more than half of novel CRFs reported in China have been first documented in Yunnan province. In the present study, based on the information available on four existing near-full-length genome (NFLG) sequences, combined with data on four other closely related sequences obtained via Basic Local Alignment Search Tool (BLAST) analysis, NFLG/subregion phylogenetic, bootscanning, and time to the most recent common ancestor (TMRCA) analyses were performed. Phylogenetic analysis revealed that the eight strains demonstrated the formation of a distinct monophyletic branch with a bootstrap value of 100%. Strains in this branch were distantly related to all known HIV-1 CRFs; it was temporarily named CRF111_01C. Bootscanning analysis revealed that CRF111_01C consisted of a CRF01_AE backbone and four inserted subtype C segments. Remarkably, CRF111_01C shared six mosaic fragment identities with the previously identified CRF100_01C. Furthermore, CRF111_01C may be deemed a potential second-generation CRF consisting of CRF100_01C and C. Coalescent Bayesian analyses revealed that the TMRCA of CRF111_01C was approximately the period 1999-2002. The emergence of such second-generation recombinants highlights that continuous molecular screening is necessary to carefully monitor the evolutionary dynamics of HIV-1 epidemics.

First Detection of a Circulating Recombinant Form of HIV-1 CRF01_AE/08_BC (CRF105_0108) with Drug-Resistant Mutations in Sichuan, China.

In this study, we identified a novel circulating recombinant form (CRF) of HIV (CRF105_0108) in a total of five patients with no obvious epidemiological linkage in Sichuan, China. Four strains were found in this study, and another strain (XC2014EU01) was reported in a previous study. The phylogenetic analysis of the five near full-length genomes showed that a CRF08_BC segment was inserted into the CRF01_AE backbone with one recombinant breakpoint in the pol region, which is the first HIV-1 CRF of CRF01_AE and CRF08_BC. Three genetic sequences had drug-resistant mutations, E138Q and V179D, indicating that there were low resistance levels to efavirenz (EFV) and nevirapine (NVP) in Liangshan Yi Autonomous Prefecture. CRF105_0108 increases the diversity and complexity of the prevalent HIV-1 CRFs in Sichuan. Simultaneously, drug-resistant mutations in this CRF may influence the efficacy of highly active antiretroviral treatments (ARTs) in Liangshan Yi Autonomous Prefecture.

Near Full-Length Genomic Characterization of a Novel Unique Recombinant (CRF01_AE/CRF07_BC) in Fuyang City of China.

Recombinant forms contribute substantially to the genetic diversity of HIV-1. Recent studies have also revealed that three major viral strains (CRF07_BC, CRF01_AE, and subtype B) have been cocirculating among men who have sex with men (MSM) in Anhui, suggesting a high probability of generating new recombinants. In this study, we reported a novel CRF01_AE and CRF07_BC HIV-1 recombinant form in MSM in Fuyang city of China. Two near full-length genome (NFLG) named FY184 and FY208 were successfully obtained. The genomic composition analysis of the NFLG reveals that it was divided into four segments by three breakpoints, with two regions of CRF07_BC inserted into a CRF01_AE backbone's gag and pol regions. The CRF01_AE regions were originated from a subcluster lineage of CRF01_AE, which is mainly circulating among MSM in China. The emergence of a novel recombinant of CRF01_AE/CRF07_BC is indicative of the increasing genetic diversity of the HIV epidemic in MSM in Anhui.

Laos is Affected by HIV CRF01_AE and the Newly Identified CRF97_01B.

Laos is the only landlocked country in Southeast Asia and borders Thailand, Myanmar and Cambodia, the three countries in this region that have been hardest hit by human immunodeficiency virus (HIV). Laos has been regarded as a low-HIV-prevalence country for decades. To understand the status of HIV in Laos in recent years, a retrospective study was performed among 2851 patients visiting a hospital in Vientiane, the capital of Laos, from November 2011 to May 2012. Whole blood samples were obtained from the patients, and DNA was extracted. HIV status was determined by HIV gag fragment-specific PCR assay. Sixty-nine samples were detected as HIV proviral DNA positive with a positive rate of 2.4% (69/2851). Sixty-one near full-length genomic sequences were obtained from the positive samples. The results of phylogenetic analysis showed that the vast majority (91.8%) of the HIV strains belonged to CRF01_AE, and the other five (8.2%) strains were identified as a new HIV circulating recombinant form CRF97_01B, which had a CRF01_AE backbone with an insertion of subtype B in the gag-pol region. Phylogeographic analysis revealed that HIV CRF01_AE circulating in Laos were multiply introduced from Thailand. These results indicated that Laos might be suffering a considerably more serious impact of HIV than previously believed. To keep this country from undergoing the same increase in HIV prevalence observed in its neighbors, immediate intervention measures and sufficient epidemiological research are urgently needed.

Identification of a Novel HIV-1 Second-Generation (CRF01_AE/B) Among Men Who Have Sex with Men in Tianjin, China.

In this study, we report a novel HIV-1 second-generation recombinant form composed of CRF01_AE and subtype B detected from a married HIV-positive male subject infected through homosexual behavior in Tianjin in northern China. The near full-length genome analyses showed that two regions of subtype B inserted into the CRF01_AE backbone with four recombinant breakpoints observed in the pol gene region. Subregion tree analyses demonstrated that the CRF01_AE regions of the recombinant were greatly clustered with the CRF01_AE subcluster 4 lineage, which was found primarily among men who have sex with men (MSM) in northern China. To the best of our knowledge, this is the first detection of a novel HIV-1 second-generation recombinant form (CRF01AE/B) in Tianjin, which indicates active transmission networks of HIV-1 infection among MSM in this region. The emergence of the novel second-generation recombinant form highlights the increasing complexity of HIV-1 epidemic among MSM population and the importance to monitor potential novel circulating recombinant forms.

Genomic Characterization of a Novel HIV-1 Second-Generation Recombinant Form (CRF01_AE/B) from Men Who Have Sex with Men in Guangxi Zhuang Autonomous Region, China.

We report here a novel HIV-1 recombinant form (18GXD4705) composed of CRF01_AE and subtype B, acquired from an unmarried HIV-positive young man subject infected through homosexual contact in Guangxi Province of eastern China. The phylogenetic analysis of the near full-length genome of 18GXD4705 indicated that one subtype B segment was inserted into the CRF01_AE backbone, with one recombinant breakpoint demonstrated in the pol region. The CRF01_AE region (I and III) of recombinant correlated with a previously reported subcluster 4 lineage. The B subregions (II) are greatly clustered together, with B strain references. The continued generation of this novel recombinant increases the genetic complexity and diversity of the HIV epidemic in Guangxi. In addition, further molecular epidemiological investigations should be conducted to continuously monitor the dynamic transmission of HIV-1 in the region.

Genomic Characterization of a Novel HIV-1 CRF01_AE/07_BC Recombinant Virus from a Married Man Who Has Sex with Men in Tianjin, China.

We report in this study a novel HIV-1 second-generation recombinant form (TJIH0172) composed of CRF01_AE and CRF07_BC isolated from a married HIV-positive male subject infected through homosexual behavior in Tianjin, China. The phylogenetic analysis of the near full-length genome of TJIH0172 reveals that one region of CRF07_BC inserted into the CRF01_AE backbone with two recombinant breakpoints observed in the vpu and env gene regions, respectively. The CRF01_AE regions (the regions I and III) of the recombinant are greatly clustered with the CRF01_AE subcluster 4 lineage, which is mainly circulating among men who have sex with men (MSM) in northern China. The CRF07_BC region (II) is clustered with two sequences (JX960600 and KF250366), which were discovered in the MSM population in Liaoning Province and Beijing city in northern China, respectively. The emergence of the novel recombinant strain from a married man who has sex with men in Tianjin, China, highlights the increasing complexity of the HIV-1 epidemic between MSM and their female partners and further molecular epidemiological investigation should be taken to track married MSM and their female partners to prevent HIV transmit from HIV high-risk populations to general populations.

Another Near Full-Length Sequence of an HIV-1 CRF01_AE/CRF07_BC Recombinant Virus from a Man Who Has Sex with Men in Tianjin, China.

Surprisingly, more new unique recombinant forms (URFs) of CRF01_AE/CRF07_BC recombinant viruses were found in Tianjin, China, recently. Here we identified another novel HIV-1 recombinant virus (TJ20170315) isolated from an HIV-1 positive man who has sex with men in Tianjin, China. Phylogenetic analysis of the near full-length genome of TJ20170315 showed that it formed a monophyletic branch within the cluster of CRF01_AE reference sequences. Recombinant analysis showed that the virus kept the CRF01_AE parental backbone, and one CRF07_BC segment was inserted into gag, pol genes of the CRF01_AE backbone. Nowadays, multiple kinds of circulating recombinant forms (CRFs) and URFs were identified among men who has sex with men in China. The emergency of URFs highlights the complexity of HIV-1 infection in Tianjin, China, and implies that the next new CRF and HIV-1 epidemic are coming on the road.

Genetic characterization and recombinant history of a novel HIV-1 circulating recombinant form (CRF101_01B) identified in Yunnan, China

The high frequency of multiple HIV-1 recombinant events among the B, C and CRF01_AE were constantly occurring in Yunnan China. Here, we characterized a novel HIV-1 circulating recombinant form (CRF) consisting of CRF01_AE and subtype B (CRF101_01B) from three epidemiologically unlinked individuals. Phylogenetic analysis based on near full length genome (NFLG) sequences revealed that CRF101_01B formed a distinct monophyletic cluster supported by a high bootstrap value of 100%, distantly related to all known HIV-1 CRFs. CRF101_01B had a CRF01_AE backbone with two B segments inserted, respectively, in the gag and pol region. Further, subregion tree analysis showed that CRF01_AE backbone and subtype B segment inserted originated from a Thailand lineage. In addition, our study found that CRF101_01B originated around the year 1996–1998. This findings described a novel HIV-1 CRF, and highlighted the importance of continual monitoring of genetic diversity and complexity of HIV-1 strains in Yunnan, China.

Identification of a Novel HIV-1 Second-Generation Recombinant Form (CRF01_AE/07_BC) in Men Who Have Sex with Men in Beijing, China.

HIV-1 CRF01_AE and CRF07_BC have been two mainly circulating HIV-1 strains in the men who have sex with men (MSM) population in Beijing for years. These two subtypes together were accounting for 78.1% of HIV-1 positive cases newly diagnosed in Beijing, 2016. In this study, we report a novel CRF01_AE/CRF07_BC second-generation unique recombinant form (URF) (named DT1427_NFLG) of HIV-1 identified in MSM population. The near full-length genome of DT1427_NFLG is about 8.8 kb with four CRF07_BC fragments inserted into the CRF01_AE backbone. In China, several novel second-generation URFs were reported in recent years and Beijing, as the capital of China, attracting a huge number of people all over the country to work and live, is confronted with the risk of the epidemic of recombinant HIV-1 strains. Therefore, it is necessary to take measures to monitor the emergency of novel recombinant of HIV-1.

Identification of a Novel HIV-1 Unique Recombinant Form Comprising CRF01_AE, Subtype B', and CRF65_cpx Among Men Who Have Sex with Men in Jilin, China.

The current HIV-1 epidemic in China is featured by diverse subtypes and continual emergence of new recombinant viruses. This study identified a novel unique recombinant form (URF), JL16013, among men who have sex with men (MSM) in Jilin, China. The JL16013 virus was different from all known subtypes and set up a distinct branch on the phylogenetic tree. This virus had a CRF01_AE backbone with two subtype B' fragments and one CRF65_cpx fragment inserted into gag, pol, env, and nef regions, suggesting that this novel URF might have originated from the CRF01_AE, subtype B', and CRF65_cpx viruses that were cocirculating in Jilin province. This was the first report of the CRF01_AE/B'/CRF65_cpx recombinant in China. Identification of this URF indicated the severity and complexity of the HIV-1 epidemic among MSM in Jilin province. Timely surveillance of new HIV-1 infections and new recombinants among the MSM population is urgently required.