Lili Chen

High genetic diversity of HIV-1 was found in men who have sex with men in Shijiazhuang, China

Men who have sex with men (MSM) have become one of the populations with severely HIV prevalence in China. However, very few genetic studies have been done on HIV-1 spreading in this population. In this study, the genetic characterization of HIV-1 strains prevalent in the MSM in Shijiazhuang, China, was analyzed basing on the HIV-1 full-length gag, pol, and partial env gene. 21 drug-naïve HIV-1 sero-positive patients were enrolled into the study. Full length gag, pol, partial env genes and some near full length genomes were amplified with nest RT-PCR followed by sequencing. Multiple subtypes, including CRF01_AE (52.9%), subtype B (35.3%) and CRF07_BC (11.8%), were found in the population. Phylogenetic analysis showed close relationship between our strains with those from Beijing MSM but not those from paid blood donors of local area. Drug resistance surveillance evaluation showed no transmitted drug resistance (TDR). However, some drug-resistance related polymorphism sites (V181I and V106I) were popularly found in B subtype strains. The findings will contribute to understanding the distribution and evolution of HIV-1 in MSM and also help the behavior change intervention.

Recombination form and epidemiology of HIV-1 unique recombinant strains identified in Yunnan, China.

Several studies identified HIV-1 recombination in some distinct areas in Yunnan, China. However, no comprehensive studies had been fulfilled in the whole province up to now. To illustrate the epidemiology and recombination form of Unique Recombinant Forms (URFs) circulating in Yunnan, 788 HIV-1 positive individuals residing in 15 prefectures of Yunnan were randomly enrolled into the study. Full-length gag and pol genes were amplified and sequenced. Maximum likelihood tree was constructed for phylogenetic analysis. Recombinant breakpoints and genomic schematics were identified with online software jpHMM. 63 (10.2%) unique recombinant strains were identified from 617 strains with subtypes. The URFs distributed significantly differently among prefectures (Pearson chi-square test, P<0.05). IDUs contained more URFs than sexual transmitted population (Pearson chi-square test, P<0.05). Two main recombinant forms were identified by considering the presence of CRF01_AE segments in full length gag-pol genes, which were B′/C and B′/C/CRF01-AE recombinants. Three clusters were identified in the ML tree which contained more than three sequences and supported by high bootstrap values. One CRF was identified. Many of URFs contained identical breakpoints. The results will contribute to our understanding on HIV recombination and provide clues to the identification of potential CRFs in China.

Genetic characterization of 13 subtype CRF01_AE near full-length genomes in Guangxi, China.

Guangxi is an important transit area for HIV transmission in South China. Characterization of the full-length genome of HIV-1 prevalent in the area is important for phylogenetic analysis and vaccine development. CRF01_AE is one of the most rapidly spreading subtypes in Guangxi. In this study, we reported thirteen near full-length CRF01_AE genomes from Guangxi, China. The nearly full-length genome was reverse transcripted and amplified in two halves with the 1-kb overlap regions. The PCR products were sequenced directly. The sequence analysis showed that all of 13 strains were CRF01_AE recombinant subtypes. Two clusters were set up with all of the sequences that grouped separately with sequences from Vietnam and Fujian, China, which strongly suggested multiple introductions of CRF01_AE strains into Guangxi province. The results will improve our understanding on the phylogenetic relationship of CRF01_AE strains in South China and also help in the development of a successful HIV vaccine.

Subtype CRF01_AE dominate the sexually transmitted human immunodeficiency virus type 1 epidemic in Guangxi, China

Human immunodeficiency virus type 1 (HIV‐1) infection by sexual transmission in Guangxi, China had increased dramatically. However, limited information is available on the genetic characterization of the HIV‐1 epidemic. In this study, HIV‐1 seropositive drug‐naïve patients infected by heterosexual transmission were enrolled. The full length gag and pol genes were sequenced followed by phylogenetic analysis, recombinant analysis and drug resistant analysis. Multiple subtypes were identified, including CRF01_AE (80.1%), CRF07_BC (6.4%), CRF08_BC (10.2%), subtype B (1.7%), and URFs (1.7%). In the phylogenetic tree, two large CRF01_AE clusters were identified. One cluster is originating from Vietnam strains as being reported previously in intravenous drug users. One novel cluster was identified and showed close relationship to strains from Fujian province. Inter‐subtype recombination among CRF01_AE, subtype B and C was identified. Low level drug‐resistance in drug‐naïve heterosexually transmitted infections was found. The results suggested that multiple originating CRF01_AE strains dominated the HIV‐1 epidemic in heterosexual transmission in Guangxi province. J. Med. Virol. 85:388–395, 2013.

Analysis of CD4+CD25+Foxp3+ regulatory T cells in HIV-exposed seronegative persons and HIV-infected persons with different disease progressions.

Regulatory T cells (Tregs) are a subset of T cells that play an important role in the regulation of T-cell function. In a previous study, CD25 was used as a marker of Tregs; however, FoxP3 was recently discovered to be a valuable phenotype of Tregs. In this study, we compared the frequency of Tregs in HIV-1-infected long-term nonprogressors (LTNP), AIDS patients (AP), HIV-exposed seronegative (ES) persons, and healthy controls (HC), by using CD4+CD25+FoxP3+ as a marker of Tregs. The results showed that the frequency of Tregs in AP was significantly higher than in the LTNP, ES, and HC, which suggests that Tregs may play a role in disease progression. Another unique finding in this study is that we found a decrease of Tregs in ES.

Identification and Characterization of Two New HIV Type 1 Unique (B/C) Recombinant Forms in China

Recombination was most important in the generation of new viral strains and in the increase of HIV diversity. There were more and more new HIV-1 strains. Not only circulating recombinant forms (CRFs) but also unique recombinant forms (URFs) have been reported around the world. CRF07_BC and CRF08_BC were the two predominant CRFs circulated in Yunnan Province, southwest China. In the present study, we identified two new HIV Type 1 unique (B/C) recombinant gorms in Yunnan Province by nucleotide sequencing in two halves of HIV genome. Although the genomic structures of the two B/C recombinants were different from previously identified CRFs (CRF07_BC and CRF08_BC) and URFs in Yunnan Pprovince, they have several common recombination sites with CRF07_BC and CRF08_BC.

Near full-length sequence analysis of a novel HIV-1 C/CRF01_AE recombinant variant from Yunnan, China.

Recombination contributes substantially to the overall genetic complexity of HIV-1, especially in populations in which multiple subtypes circulate. Yunnan is a province in China with most severely HIV epidemic where many subtypes and CRFs of HIV-1 are circulating. In this study, we report a novel HIV-1 recombination involving C and CRF01_AE. The near full-length genome was reverse transcripted and amplified in two halves with the 1 kb overlap regions. The PCR products were sequenced directly after purification. Sequence analysis showed that the majority of the genome was CRF01_AE, three fragments of C subtype were inserted along the genome in gag and pol region. This is the first report of a novel recombination involving subtype C and CRF01_AE in Yunnan, China. More work is needed to check the epidemiologic significance of the new recombination.

Similar neutralizing activity in the HIV-1 infected long term non-progressors(LTNPs) and typical progressors(TPs)

Neutralizing antibodies are considered to be an important protective parameter used in HIV-1 vaccine evaluation. However, the exact role that neutralizing antibodies plays in controlling the disease progression of HIV-1 infected peoples is still undetermined. In this paper, we compared the protective function of the neutralizing antibody response in the plasma from LTNP and TP against clade B and clade C pseudoviruses. No difference in the neutralizing activities between the plasma from LTNP and TP was found, which was consistent with the most recent reports. In addition, no correlations between the titer or breadth and CD4+ or viral load in HIV-1 infected individuals were found. The protective roles played by neutralizing antibodies in controlling disease progression of HIV-1 infected people need to be considered in a new viewpoint.