Second-Generation Recombinant Form Research Articles

Near Full-Length Genomic Characterization of Two Novel HIV Type 1 Second-Generation Recombinant Forms (CRF01_AE/CRF07_BC) from Guangxi, China.

CRF01_AE and CRF07_BC are the two predominant HIV-1 subtypes currently circulating in China. We identified here a novel CCR5-tropic HIV-1 second-generation recombinant form virus found in two individuals, (GX19017 and GX19032), which were isolated from two HIV-1-positive people in Guangxi, southwest China. Phylogenic analyses indicated that these two sequences were all composed of two well-established circulating recombinant forms (CRFs) CRF07_BC and CRF01_AE, with four recombinant breakpoints observed in the pol, vpu/env, and env gene regions, respectively. The recombinant CRF01_AE region was clustered with the previously described CRF01_AE subcluster 2 lineage, which was characterized by the susceptibility to phenotypic transfer. The genome structure is significantly different from other previously reported CRFs and unique recombination forms. The emergence of a series of novel recombinant strains is indicative of the burgeoning complexity of the HIV-1 epidemic among the sexually transmitted population. Meanwhile, it may furnish significant insights into the dynamics and intricacy of the HIV-1 epidemic in China.

Identification of a novel HIV-1 second-generation circulating recombinant form (CRF136_0107) among men who have sex with men in China.

To investigate the molecular epidemiology of HIV-1 in Heilongjiang, China, and try to spot signs of new circulating recombinant form (CRF) in this region. A molecular epidemiological study was conducted in Heilongjiang, China during 2011-2020. Plasma samples were collected from three HIV-1 positive patients. The near full-length genome sequences (NFLGs) of a novel circulating recombinant form (CRF) were then obtained and subjected to phylogenetic analysis using Mega 7.0.26. Recombination analysis was performed by the jumping profile Hidden Markov Model (jpHMM). Finally, the origin time of this novel CRF was inferred using the Bayesian phylogenetic analysis in Beast v1.10.4. The three NFLGs formed a distinct monophyletic cluster in the neighbor-joining (NJ) tree. Recombination analysis revealed that the recombinant genome was composed of five segments derived from CRF01_AE, subtypes B, and C, but further confirmed to be a second-generation recombinant form of CRF01_AE/CRF07_BC by a comparison of genome maps and subregion phylogenetic analysis and therefore designated as CRF136_0107. With Bayesian phylogenetic analysis, CRF136_0107 was estimated to originate around 2010-2011. A novel HIV-1 CRF01_AE/CRF07_BC second-generation CRF called CRF136_0107 was identified among men who have sex with men (MSM) in Heilongjiang, a northeast province of China.

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 a New HIV-1 CRF68_01B/CRF01_AE Recombinant Form Among Men Who Have Sex with Men in Hebei Province, China.

In recent years, homosexual contact has been the most frequent route of human immunodeficiency virus type one (HIV-1) transmission in Hebei, China. The number of circulating recombinant forms (CRFs) and unique recombinant forms found in this key population were more and more. In this study, we identified a novel HIV-1 second-generation recombinant form originated from CRF68_01B and CRF01_AE among men who have sex with men (MSM) through the phylogenetic and recombinant breakpoints analyses based on the near full-length genome. Both CRF68_01B and CRF01_AE were circulating in the Hebei province of China, and this MSM was diagnosed as the recent HIV-1 infection in fact. The result reminds that we should constantly monitor HIV-1 diversity in Hebei and take further effective to control the recombination of not only HIV-1 major strains but also minor strains.

Characterization of a New HIV-1 CRF01_AE/B Recombinant Virus Form Among Men Who Have Sex with Men in Baoding, Hebei, China.

We analyzed the near full-length genome (NFLG) of an HIV-1-positive sample(027A) with an undetermined subtype to determine the recombinant characteristics and possible source of the parental virus. 027A is a novel HIV-1 second-generation recombinant form composed of CRF01_AE and subtype B, detected from a married HIV-1-positive male subject who was infected through homosexual transmission in Baoding, Hebei province, China. The NFLG phylogenetic tree analysis suggested that the strain was close to circulation recombinant forms' (CRFs') reference sequences involved with CRF01_AE, but formed a distinct monophyletic cluster separately from them. This indicated that the strain might be a unique CRF01_AE-related recombinant from. Furthermore, the results of RIP and jpHMM further demonstrated that the NFLG sequence of the strain was composed of CRF01_AE and subtype B. The strain was two CRF01_AE fragments inserted into B backbone. Phylogenetic analysis illustrated that the CRF01_AE subregions were from the previously identified CRF01_AE cluster 4, and the B subregions were correlated with the B strains originated from Europe and America. They were all the lineages widely prevalent in men who have sex with men (MSM) population in China. In recent years, a large number of recombinant originated from CRF01_AE and B strains are constantly emerging in MSM population in China. This continual and recurrent recombination between CRF01_AE and B in high-risk group people deserves more attention and further monitoring.

Genetic Characterization of a Novel HIV-1 Second-Generation Recombinant Form Originating from CRF86_BC and a Unique Recombinant Form in Yunnan, China.

Yunnan is the first place where human immunodeficiency virus type 1 (HIV-1) became prevalent in China, and it is also the place with the most complicated HIV-1 genetic diversity in China. On October 23, 2019, a patient newly diagnosed with acquired immunodeficiency syndrome from a hospital in Baoshan, Yunnan, was recruited for genetic analysis. Near full-length genome of HIV-1 was amplified from the plasma sample. Phylogenetic analysis revealed that this sequence (BS6F24) has a close relationship with CRF86_BC and a unique recombinant form (URF) (KY406739), which was formed by recombination of subtypes B and C. Bootscan analysis confirmed that the first part (HXB2:1022-5832) and last part (HXB2:5833-9120) genomes of BS6F24 had the same recombinant structures as KY406739 and CRF86_BC, respectively. A second-generation recombinant form that originated from CRF86_BC and a URF were reported for the first time. This indicates the need for continuous monitoring of the genetic diversity of HIV-1 in Yunnan, China.

Genetic Characterization of a Novel HIV-1 Second-Generation Recombinant Form (CRF01_AE/CRF07_BC) Identified in Yan'an City, China.

Owing to co-epidemic of CRF01_AE and CRF07_BC in China, increasing numbers of the second-generation recombinants between them have been identified especially among sexual population. In this study, we identified a unique CRF01_AE/CRF07_BC recombinants from a male HIV-1 positive individual (18YA004) infected by heterosexual contact in Yan'an city, Shaanxi province. The near full-length genome analyses showed 18YA004 was divided into six fragments by five breakpoints located in the pol, vpr, vpu, and nef gene, respectively. Three CRF01_AE segments (segments I, III, and V) were all clustered within the cluster 4a lineage, exclusively circulating among MSM in the northern China. Coupled with our previous finding of CRF01_AE/C recombinant in Yan'an city, the emergence of CRF01_AE/CRF07_BC strain further suggested coexistence of multiple HIV-1 genotypes here. Therefore, it is necessary to continue monitoring the molecular epidemiology of HIV-1 among high-risk groups to obtain a better understanding of the genetic complexity and transmission of HIV-1 in this region.

The Genetic Diversity of HIV-1 Within Antiretroviral-Naive Outpatients in Ganzhou, China.

To explore the molecular epidemiological status of human immunodeficiency virus type 1 (HIV-1) in Ganzhou, China, eight HIV-1-positive outpatients were recruited from July 5 to 21, 2018. Six HIV-1 near-full-length sequences were amplified and sequenced from the plasma samples that were collected before the patients' antiretroviral treatments. Phylogenetic and bootscan analyses revealed that one of the sequences was CRF01_AE, one was CRF55_01B, and two were CRF07_BC. Notably, one of the sequences was a unique recombinant form, and one of them was a second-generation recombinant form of CRF07_BC and subtype C. These results revealed that multiple HIV-1 subtypes are circulating in Ganzhou, China. Systematic surveys with large sample sizes are urgently needed to explore the exact molecular epidemiological characteristics and to trace the origins of HIV-1 in Ganzhou, China.

Genomic Characterization of a Novel HIV Type 1 Strain Originating from CRF07_BC and CRF01_AE by Heterosexual Transmission in the Lingshan Prefecture of Guangxi Province, China.

Recently, an increasing number of circulating recombinant forms (CRFs) and unique recombinant forms of HIV-1 have been identified in China, contributing substantially to the genetic variability of this virus. This study reports a novel second-generation recombinant form of HIV-1 (GX2015QZLS204), composed of segments from the CRF07_BC and CRF01_AE strains, which was isolated from an HIV-positive male individual infected through heterosexual contact, while residing in the Guangxi province of southwest China. Analysis of the near full-length genome sequence showed that one segment of the CRF01_AE virus subtype was inserted into the CRF07_BC subtype backbone. Recombination analysis demonstrated that the genome of GX2015QZLS204 was separated into seven segments with six breakpoints. Subregion trees constructed by the neighbor-joining method confirmed that the CRF01_AE segment was from the previously identified CRF01_AE cluster 2, and the CRF07_BC segment correlated with the CRF07_BC strain originating from the Jiangxi and Xinjiang provinces of China. The emergence of GX2015QZLS204 highlights the frequent generation of novel recombinant forms and the increasing complications of the HIV-1 epidemic among heterosexual transmission (HET) groups in China. This highlights the importance of monitoring HIV-1 molecular epidemiological characteristics and the urgent need for reduction of the HIV-1 epidemic among HET groups in China.

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.

Characterization of a Novel HIV-1 CRF01_AE/CRF07_BC Recombinant Virus Form in Guizhou, China.

We identified a novel CRF01_AE and 07_BC HIV-1 recombinant form in Guizhou province in southwest China. The phylogenetic analysis of the near full-length sequence reveals that it was divided into five segments by four breakpoints, and the CRF01_AE regions of the recombinant were clustered with subcluster 4 lineage of CRF01_AE, which mainly circulated among men who have sex with men (MSM) in China. The CRF07_BC regions of the recombinant were clustered with CRF07_BC lineage, which circulated among Chinese MSM. This is the first detection of a novel HIV-1 second-generation recombinant form (CRF07_BC/CRF01_AE) in Guizhou, which shows the increasing significance of heterosexual transmission contributing to the complexity of the HIV-1 epidemic in southwest China, and more effort measures should be taken to monitor the genetic evolution of HIV-1 strains and prevent HIV-1 transmissions.

Genomic Characterization of a New HIV-1 CRF01_AE/CRF07_BC Recombinant Virus Form in Guizhou in Southwest China.

A novel HIV-1 second-generation recombinant form (CRF01_AE/CRF07_BC) was isolated from an HIV-positive subject among men who have sex with men (MSM) in Guizhou province in Southwest China. Recombinant analyses of the near full-length genome suggested that the strain was composed of CRF01_AE and CRF07_BC with one region of CRF07-BC inserted into a CRF01-AE backbone. Further analysis indicated that the CRF01_AE regions of the recombinant were highly clustered together with a subcluster 4 lineage of CRF01_AE, which is exclusively circulating among MSM in China. The CRF07_BC region of the recombinant was clustered with the CRF07_BC cluster, which was identified among MSM. The emergence of the novel HIV-1 recombinant may be a harbinger of more novel intersubtypes recombinants occurring in Guizhou province in Southwest China, and was of great important in understanding the dynamics and complexity of the HIV-1 epidemic in this region.

Characterization of a Novel HIV-1 CRF01_AE/CRF07_BC Recombinant Virus Among Men Who Have Sex with Men in Tianjin, China.

We report here a novel human immunodeficiency virus type 1 (HIV-1) second-generation recombinant form comprising CRF01_AE and CRF07_BC isolated from an HIV-positive male subject infected among men who have sex with men (MSM) in Tianjin in north China. The phylogenetic analysis of the near full-length genome of TJIH0345 reveals that three regions of CRF01_AE were inserted into the CRF07_BC backbone with five recombinant breakpoints observed in the pol, vif, vpu, and env gene regions whose genome structure is distinctly different from other circulating recombinant forms and unique recombinant forms previously reported. The continued emergence of the novel recombinant strain in Tianjin, China, highlights the increasing complexity of the HIV-1 epidemic among the MSM population, and further molecular epidemiological investigation should be done to track the genetic evolution of HIV-1 strains to prevent HIV transmission.

Genomic Characterization of a Novel HIV-1 Second-Generation Recombinant Form (CRF01_AE/07_BC) from a Married Man Who Has Sex with Men in Zhejiang, China.

We report here a novel HIV-1 recombinant form detected from a married HIV-positive man infected through homosexual behavior in Zhejiang, China. The breakpoint analysis of near full-length genome demonstrated a complex genome organization comprising two circulating recombinant forms (CRFs), CRF01_AE and CRF07_BC, both well-known CRFs in China. The parental CRF01_AE region (II) of recombinant clustered together with a previously reported cluster 4 lineage. The CRF07_BC regions (I and III) clustered within CRF07_BC references. The ongoing generation of intersubtype recombinant viruses increases the complexity of the HIV-1 epidemic and illustrates the necessity of persistent surveillance of the transmission of HIV-1.

Near Full-Length Genome Sequence of a Novel HIV-1 Second-Generation Recombinant Form (CRF01_AE/CRF07_BC) Detected Among Men Who Have Sex with Men in Tianjin, China.

In recent years, men who have sex with men (MSM) have been the most affected population with fastest growing human immunodeficiency virus (HIV) prevalence in China. In our study, a novel CRF01_AE/07_BC HIV-1 recombinant form (TJIH0069), with four unique breakpoints in the pol, vpr, and nef gene regions, was identified among MSM in Tianjin City in north China. The CRF01_AE regions (regions I, III, and V) of the recombinant are all clustered together with a previously described sequence (HQ215555), which was exclusively circulating among MSM in Shijiazhuang city of Hebei Province in north China. The CRF07_BC regions (II and IV) are clustered with BJ070032 and JX960600, which were discovered from MSM population in north China. The continuous emergence of a similar pattern of recombinant strain between the two MSM-adapted existing circulating recombinant forms (CRFs) highlights the importance to monitor potential new CRFs for early and precise control and prevention.

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.

Characterization of a Novel HIV-1 Second-Generation Recombinant Form in Men Who Have Sex with Men in Beijing, China.

Cocirculation of multiple subtypes in the same population contributes significantly to the emergence of recombinant viruses. BJ2015EU19, a novel CCR5-tropic human immunodeficiency virus (HIV)-1, second-generation recombinant virus, was isolated from a man who has sex with men in Beijing, China. Phylogenetic analysis of the near full-length genome showed that BJ2015EU19 consisted of seven fragments from CRF01_AE and CRF07_BC. There were six recombinant breakpoints in the pol, vpu, env, and nef genes of BJ2015EU19, which were different from the other circulating recombinant forms and unique recombinant forms (URFs). The new emergence of the URF increases the complexity of the HIV epidemic in the Chinese homosexual group, and the ongoing generation of recombinant viruses may provide an important basis for future analysis of the recombination mechanism of HIV-1.