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Background: Due to the deficiencies of vaccines and effective medicine, the human immunodeficiency virus (HIV) infection mechanism should be studied. The C19orf66 gene, one of the interferon-stimulated genes (ISGs), expresses broad-spectra anti-viral activity, including inhibiting HIV replication., Methods: In this study, we collect 421 HIV-1 infected patients and 448 controls to genotype three SNPs in the C19orf66 gene. Then, the association between SNPs and biochemical indices/ HIV-1 subtypes are analyzed., Results: Genotypes CC and CT of rs12611087 show statistically lower and higher frequencies in HIV-1 infected patients than in controls, respectively. Alleles C and T of rs12611087 play protective and risk roles in Yunnan HIV population, respectively. Biochemical indices analysis shows that HIV-1 infected persons carried genotype TT of rs77076061 express significantly lower CD3 + /CD45 + ratio level and higher IBIL level. The epidemic subtypes of HIV-1 patients in this study are CRF 07_BC and CRF 08_BC. Moreover, subtype CRF 08_BC tends to infect persons with genotype CC of rs12611087., Conclusion: The genetic polymorphisms of the C19orf66 gene are firstly studied and reported to associate with HIV-1 infection and biochemical indices of patients in Yunnan. Furthermore, subtype CRF 08_BC infection could be influenced by genotypes of SNP in the C19orf66 gene., Competing Interests: The authors declare there are no competing interests., (©2023 Zhang et al.)

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., (Copyright © 2021. Published by Elsevier B.V.)

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., (Copyright © 2019. Published by Elsevier B.V.)

Background: The overall success of Human immunodeficiency virus type 1 (HIV-1) antiretroviral therapy (ART) was heavily challenged upon the occurrence of drug resistance. Dehong Prefecture witnessed not only the first report of HIV-1 infection but also the experimental adoption of antiviral treatment in China. The transmission and epidemic of HIV-1 in Dehong is impacted by cross-border activities. The characteristics of HIV-1 drug resistance among therapy-naïve Burmese entering travelers in Yunnan and their speculated origin are still not clarified., Methods: Two hundred ninety-eight HIV-1 infected Burmese entering travelers at Dehong ports were recruited between 2003 and 2012. The partial HIV-1 pol gene fragments were amplified and sequenced for the analysis of drug-resistance mutations (DRMs). Phylogenetic analysis on gag-pol gene was conducted to elucidate phylogenetic and evolutionary characteristics of these drug resistant strains., Results: It was figured out that the occurrence ratio of HIV-1 drug resistance among HIV-1 infected entering travelers from Myanmar was up to 12.8%. The resistant mutations covered several types, including one type of PI mutations (L33F), six types of NRTI mutations and seven types of NNRTI. Close genetic relationship was observed in the phylogenetic analysis on gag-pol gene among the drug resistant strains respectively from Dehong, other Yunnan areas, neighboring provinces (Guangxi) and neighboring countries (Thailand and Myanmar)., Conclusions: The findings in this study revealed that HIV drug resistant locus is spreading from the population who is receiving drug-resistance treatment to the new infectors, which indicates the urgency of surveillance work on drug resistance among the migrant population with high risks of HIV infection.

Currently, complex HIV-1 recombinations among the B', C, and CRF01_AE genotypes have frequently arisen in Yunnan, China. A novel HIV-1 complex circulating recombinant form (CRF) consisting of B', C, and CRF01_AE (CRF96_cpx) was recently characterized from three epidemiologically unlinked individuals. Two strains of them were isolated from the injecting drug users in this study, the remaining one strain (JL. RL01) was obtained from a previous report in Jilin province. Phylogenetic analysis based on near full-length genome revealed that CRF96_cpx formed a distinct monophyletic cluster supported by a high bootstrap value of 100%, distantly related to all known HIV-1 subtypes/CRFs. CRF96_cpx had a CRF01_AE backbone with three subtype B' and C segments inserted, respectively, in the gag and pol region. Furthermore, subregion tree analysis showed that CRF01_AE backbone and subtype B segment inserted originated from a Thai-CRF01_AE lineage, whereas subtype C fragment inserted was from an India C lineage. They are different from previously documented CRF01_AE/B/C forms in its distinct backbone, inserted fragment size, and breakpoints. This highlighted the importance of continual monitoring of genetic diversity and complexity of HIV-1 strains in Yunnan, China.

Due to the open policy of the Chinese government, a large number of Burmese individuals enter China at land ports in Yunnan province for travel or business. However, the situation of HIV-1 infection and its phylogenetic characteristics among these travelers remains unclear, which is a potential threat to public health. From January 2003 to December 2012, a total of 1,961 travelers were detected to be positive for HIV-1 infection at land ports between Myanmar and Yunnan province, China. From 1153 (58.8%) Burmese of them, we randomly collected 489 serum samples for HIV-1 subtype/recombinant analysis. Based on successfully obtained 223 gag-RT sequences, 187 of them were genotyped as 2 subtypes and 3 CRFs. CRF01_AE was showed to be the most prevalent genotype (54.3%), followed by subtypes C (13.5%) and B (10.8%). Notably, CRF07_BC (1.3%) and CRF08_BC (4.0%) were mainly distributed in travelers from Shan state and Kachin (91.7%, 11/12), but was not found in travelers from the capital city of Yangon (0/16). Additionally, there were 36 samples (16.1%) were preliminary determined as unique recombinant forms (URFs). The higher HIV-1 infection among entering travelers from Myanmar and its diverse and complex genotypes distribution suggest this bridge population may facilitate the transmission of HIV-1. It is necessary to have the strict monitoring on this population for prevention of HIV-1 cross-border transmission., (© 2017 Wiley Periodicals, Inc.)

Xishuangbanna is a popular tourist destination in southern Yunnan Province, bordering with Vietnam and Laos, and Myanmar. There are more than 2 million cross-border travelers annually entering China at two land ports, Daluo and Mohan. To clarify the characteristics of HIV-1 prevalence among entry travelers, a retrospective epidemic investigation was conducted. Between 2003 and 2012, 196 among 91 432 entry travelers were detected to be HIV-1-positive, accounting for infection rate of 0.21%. Eighty-one gag-pol gene sequences were obtained for phylogenetic analyses and subsequent recombination analysis. It was shown that the most prevalent HIV-1 subtype in this population was circulating recombinant form (CRF) 01_AE (42, 51.86%), followed by CRF08_BC (17, 20.99%), CRF07_BC (4, 4.94%), B' (2, 2.47%), C (2, 2.47%), other recombinants (9, 11.11%), and undefined subtype (5, 6.17%). HIV-1 genotype distribution among travelers entering at two land ports is different, CRF01_AE and CRF08_BC accounted for a larger percentage among individuals from Daluo, whereas the proportions of subtype C and undefined URFs were larger among individuals from Mohan. The undefined subtype indicates the occurrence of novel HIV-1 subtype or CRF. This finding is useful for developing of AIDS prevention strategies., (© 2016 Wiley Periodicals, Inc.)

In recent years, multiple circulating recombinant forms (CRFs) and unique recombinant forms of human immunodeficiency virus type 1 (HIV-1) have been described in Yunnan, China. Here, we identified a novel HIV-1 CRF (CRF86_BC) isolated from three heterosexuals with no obvious epidemiologic linkage in western Yunnan (Baoshan prefecture) in China. CRF86_BC had a subtype C backbone with four subtype B fragments inserted into the pol, vpr, vpu, env, and nef gene regions, respectively. Furthermore, subregion tree analysis revealed that subtype C backbone originated from an Indian C lineage and subtype B segment inserted was from a Thai B lineage. They are different from previously documented B/C forms in its distinct backbone, inserted fragment size, and break points. This highlighted the importance of continual monitoring of genetic diversity and complexity of HIV-1 strains in this region.

We report a novel HIV circulating recombinant form (CRF78_cpx) composed mainly of CRF01_AE with inserts from subtypes B and C identified from three epidemiologically unlinked individuals in Yunnan province, China. Two of the subjects are heterosexual men and one is a male intravenous drug user. Sequencing and analyzing the near-full-length genome of these three isolates (YNTC88, YNTC19, and YNTC35) revealed identical recombination breakpoints in all three viruses, but considerable genetic diversity between them, across the genomes, indicating that this is not a newly created CRF, only newly detected. CRF78_cpx differs from previously documented CRF01-AE/B'/C forms in its distinct backbone, inserted fragment size, and breakpoints, and is not related to other described recombinants in the region such as CRF07_BC or CRF65_cpx (also composed of CRF01_AE, B', and C). Our present findings further enrich the diversity of the prevalent HIV-1 CRFs in Yunnan, which is considered as an epicenter of HIV-1 infections in China.

The aim of this study was to assess HIV-1 prevalence and the distribution of HIV-1 subtypes among travelers crossing the border at the HeKou land port. Between 2003 and 2012, 22,799 persons were randomly recruited from people entering China from Vietnam. In this crossing border population, a total of 161 (0.71%) travelers were determined as HIV-1-positive. From them, 140 HIV-1-positive serum samples were collected for RNA extraction and subsequent RT-nested PCR amplification of the group-specific antigen (gag)-RT with a length of 2.6 kb. The DNA sequences were analyzed to determine the HIV-1 subtypes/recombinants. We found that the circulating recombinant form 01_AE (CRF01_AE) was the most common HIV-1 subtype, accounting for 49.4% (41/83) of the subtyped 83 samples, followed by CRF08_BC (26.5%, 22/83) and CRF07_BC (7.2%, 6/83). Only 1 sample was classified as subtype C. Thirteen cases could not be clustered into any known subtypes or CRFs and presented as unique recombinant forms (URFs). Of them, 6 recombination patterns were identified. They had distinct structures consisting of fragments of subtypes B, C, CRF01_AE, CRF07_BC and CRF08_BC. Between 2003 and 2012, CRF01_AE and CRE08_BC were shown to be the most prevalent recombinant forms identified each year. But yearly change of each subtype is uncertain regular among in these travelers during the past decade. Understanding the distribution of HIV-1 subtypes/recombinants and how it changes across time among individuals entering China from Vietnam through this land port is crucial to establish strategies for the prevention of HIV cross-border transmission., (© 2015 Wiley Periodicals, Inc.)

Background: Yunnan is not only considered the region with the most concerning human immunodeficiency virus (HIV)-1 prevalence, but is also the central hub for the spread of HIV-1 from Southeast Asia to the other provinces of China. Yunnan has the highest proportion of entry travelers who have transmitted HIV from neighbored Southeast Asian countries to mainland of China., Methods: Between 2003 and 2012, we recruited 280,961 entry travelers at land ports located in 7 bordering prefectures respectively in the Yunnan Province for HIV-1 screening. Based on the detection of HIV-1 antibody, the HIV-1 infection rate was determined., Results: Among the recruited entry travelers, 2380 were determined HIV-1 positive with infection rate of 0.85%. Travelers entering the Dehong port had the highest HIV-1 infection rate (5.12%), followed by those entering Baoshan (0.88%), Lincang (0.83%), and Honghe (0.71%). For all HIV-1 positive cases, travelers aged 21-30 and 31-40 were the most commonly infected individuals, accounting for 38.45% and 37.77% of all cases, respectively. The most common occupation of the infected population was driver (42.38%), and the proportion of industrials had increased yearly. Based on the reported risk factors, sexual transmission was the main HIV-1 infection route (77.11%) of this population., Conclusions: We have clarified the rate of HIV-1 infection among this bridge population. The characteristics of HIV-1 positive population and high geographical heterogeneity have provided the necessary epidemiological data for monitoring the HIV-1 epidemic among cross-border travelers in Yunnan and to further understand the cross-border spreading of the HIV-1 infection.

To assess the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and to investigate their mutual influences on infection status among human immunodeficiency virus type 1 (HIV-1)-seropositive injection drug users (IDUs). A cross-sectional study was conducted among HIV infected IDUs in Dali, China. The participants were tested for serological markers of HBV and HCV infection, alanine transaminase (ALT) activity and CD4(+) T cell count. HCV genotype was determined by sequencing. Of 529 patients, 498 (94.1 %) HIV infected IDUs agreed to participate. The overall prevalence of HCV infection (anti-HCV antibody positive) and spontaneous HCV clearance were 90.8 % (452/498) and 21.5 % (97/452), respectively. Of 411 subjects who had not received HBV vaccine, 296 (72.0 %) were positive for antibody against HBV core antigen (HBcAb), while 274 (66.7 %) were positive for both HCV antibody and HBcAb. HBV antigens were detected in 52 of the HBV-infected subjects (17.6 %). HCV clearance was associated with HBV antigenemia (p = 0.0002) and higher CD4(+) T cell count (p = 0.0294). Resolved HBV infection was associated with HCV genotype 3 (p = 0.0365). HBV and HCV infection are highly prevalent and mutually influence infection status in HIV-1 infected IDUs in Dali, China.

Type 1 human immunodeficiency virus (HIV-1) and hepatitis C virus (HCV) are deadly bloodborne-transmitting pathogens. Due to sharing the routes of transmission, co-infection of HIV-1 and HCV is common with a high rate. Co-infection of HCV affects morbidity and mortality of patients with AIDS and impairs their tolerance to antiretroviral therapy. In this study, the roles of HCV proteins in the regulation of HIV-1 replication and the molecular mechanism involved in such regulation were investigated. We demonstrated that HCV NS3 protein stimulated HIV-1 LTR transcription and that HIV-1 Vpu protein was required for the activation of HIV-1 transcription regulated by HCV NS3/4A complex. Further study revealed that Vpu mediated ubiquitination-associated degradation of NS4A, detached NS3/4A complex and release NS3 for nuclear translocation. Since both degradation of NS4A and activation of HIV-1 LTR were closely correlated and mediated by Vpu, we proposed that Vpu impairs the stability of NS4A and releases NS3 from NS3/4A complex for the stimulation of HIV-1 transcription. This study enriched our understanding on HIV-1/HCV co-infection and provided new insights in molecular mechanism involved in the co-infection of the two viruses., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The Yunnan province is the epicenter of HIV-1 epidemics in China and a center for drug trafficking to the other parts of the world. In six prefectures of this province, a total of 132 IDUs were recruited to determine the sero-prevalence of HCV and HIV-1 and the positive rates were 93.94% and 68.18%, respectively (P<0.001). Co-infection with HCV and HIV-1 was found among 89 IDUs, of whom several HCV fragments were amplified and sequenced. Sequences of the HCV 5'NCR-C and NS5B region were determined from 82 IDUs. Phylogenetic analyses showed consistent genotyping among 80 IDUs. Among them HCV genotypes 1a, 1b, 3a, 3b, 6a, 6n, and a tentatively assigned novel 6u subtype were found in 1 (1.25%), 16 (20%), 19 (23.75%), 24 (30%), 4 (5%), 9 (11.25%) and 7 (8.75%) individuals, respectively. In two IDUs, genotyping results were discordant, suggesting mixed HCV infections or recombination. The proportion of patients with HCV 1b tended to decrease from the north to south and from the east to west in this province. Genotype 3 and 6 strains were more frequent in the southern prefectures. The novel subtype 6u strains were only detected in Dehong which borders Myanmar. Our findings showed a unique pattern of HCV genotype distribution, which is similar to that in the southeastern Asian countries but distinct from that among the general population in China. Routes of drug trafficking and the resulting high prevalence of HIV-1 infection may have contributed to this pattern of HCV genotype distribution.

Molecular epidemiological investigation was conducted among injecting drug users (IDUs) (n = 11) and heterosexuals (n = 15) in Kunming, Yunnan Province of China. HIV-1 genotypes were determined based on the nucleotide sequences of 2.6-kb gag-RT region. The distribution of genotypes among IDUs was as follows: CRF07&#95;BC (5/11) and CRF08&#95;BC (5/11); subtype B' (1/11). Similarly, a majority of Kunming heterosexuals (14/15) were infected with CRF07&#95;BC (4/15), CRF08&#95;BC (6 /15), or subtype B' (4/15), known to predominate among IDUs in China. This contrasts with trends in the coastal regions of China and surrounding southeastern Asian countries, where CRF01&#95;AE predominates among heterosexuals. The heterosexual HIV-1 epidemic in Kunming thus appears to derive from the local IDU epidemic. Of note, subtype B' was the most prevalent strain among heterosexuals before 1997, while CRF07&#95;BC and CRF08&#95;BC became predominant in 2002, indicating a transition of HIV-1 genotype distribution between the early and the more recent samples from Kunming heterosexuals.

We identified a new class of human immunodeficiency virus type 1 (HIV-1) recombinants (00CN-HH069 and 00CN-HH086) in which further recombination occurred between two established circulating recombinant forms (CRFs). These two isolates were found among 57 HIV-1 samples from a cohort of injecting drug users in eastern Yunnan Province of China. Informative-site analysis in conjunction with bootscanning plots and exploratory tree analysis revealed that these two strains were closely related mosaics comprised of CRF07&#95;BC and CRF08&#95;BC, which are found in China. The genotype screening based on gag-reverse transcriptase sequences of 57 samples from eastern Yunnan identified 47 CRF08&#95;BC specimens (82.5%), 5 CRF07&#95;BC specimens (8.8%), and 3 additional specimens with the novel recombinant structure. These new "second-generation" recombinants thus constitute a substantial proportion (5 of 57; 8.8%) of HIV-1 strains in this population and may belong to a new but yet-undefined class of CRF. This might be the first example of CRFs recombining with each other, leading to the evolution of second-generation inter-CRF recombinants.

Objectives: To investigate the molecular epidemiology of HIV in China's Yunnan Province, where the initial HIV-1 outbreak among injecting drug users (IDU) occurred in 1989, and to analyse the genesis and interrelationship of the epidemic with that in surrounding areas., Design: A molecular epidemiological investigation was conducted among IDU in three prefectures in Yunnan Province, including Wenshan (east), Honghe (southeast) and Dehong (west)., Methods: Thirty-nine specimens were collected from consenting IDU in 2000-2001. The nucleotide sequences of 2.6 kb gag-RT and 340 base pair (bp) env (C2/V3) regions were determined. Phylogenetic tree and recombination breakpoint analyses were performed., Results: The circulating recombinant form (CRF), CRF08&#95;BC, predominated in east Yunnan near Guangxi Province (89% in Wenshan and 81% in Honghe), whereas it was not detected in Dehong (0/14) in the west. In contrast, 71% (10/14) of the Dehong isolates were unique recombinant forms (URF), mostly between subtypes B' (Thailand variant of subtype B) and C, with distinct profiles of recombination breakpoints. The subtype B' accounts for the remaining 29% (4/14) of Dehong isolates. Interestingly, two Honghe isolates (2/16) shared some of the precise B'/C recombination breakpoints with CRF07&#95;BC., Conclusion: New recombinant strains are arising continually in west Yunnan near the Myanmar border. Some appeared to be secondary recombinants derived from CRF07&#95;BC that had further recombined with other strains. The uneven distribution of subtypes, CRF and URF, suggests the presence of independent transmission networks and clusters among IDU in Yunnan.

The southeastern region of Yunnan province is a key site for drug trafficking and HIV-1 infection spread from the west of Yunnan and Laos to southeastern China. To investigate the prevalence of HIV-1 infection and hepatitis C virus (HCV) coinfection among injection drug users (IDUs) in southeastern Yunnan, three cohorts of 285 addicts, including 242 IDUs and 43 oral drug users, living in the cities of Gejiu and Kaiyuan and the county of Yanshan were studied. HIV-1 and HCV infections were detected by enzyme-linked immunosorbent assay and/or polymerase chain reaction. Data on the age, sex, risk behavior, drug use history, employment, ethnic background, and marriage status were obtained by interview. The overall prevalence of HIV-1 infection was 71.9%. The rate of HCV coinfection among 138 HIV-1-infected IDUs was 99.3%. Most HIV-infected IDUs were 20 to 35 years old (86.7%) and were ethnic Han (75.9%), suggesting that the epidemic in Yunnan is no longer confined to non-Han ethnic minorities. HIV prevalence in female IDUs (81.2%) was significantly higher than in male IDUs (68.2%) ( p <.05). The prevalence of HIV infection reached 68.4% after 1 year of injection drug use. Needle/syringe sharing is the major high risk factor for the spread of HIV-1 and HCV infections. Large-scale educational campaigns are urgently needed to reduce the spread of HIV and HCV infection in these regions.