Liying Ma

Chinese Center For Disease Control and Prevention

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Yiming Shao

Jining Medical University

Shibo Jiang

Tsinghua University

Yan Wang

Shandong University

Weisi Xu

Chinese Center For Disease Control and Prevention

Kunxue Hong

Nanjing Medical University

Yi Feng

Shandong Center for Disease Control and Prevention

Desheng Kong

Hebei Medical University

Hui Xing

State Key Laboratory of Infectious Disease Prevention and Control

Yuan Lin

Chongqing Medical University

Yiming Shao

National Center for AIDS/STD Control and Prevention,China CDC

Cooperative Institutions

Chinese Academy of Sciences

106

Peking University

Chinese Center For Disease Control and Prevention

Chinese Academy of Medical Sciences & Peking Union Medical College

Capital Medical University

Fudan University

University of Chinese Academy of Sciences

National Center for AIDS/STD Control and Prevention,China CDC

Shanghai Jiao Tong University

Sun Yat-sen University

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Escape from humoral immunity is associated with treatment failure in HIV-1-infected patients receiving long-term antiretroviral therapy

Scientific Reports (2017)

Yabo Ouyang Qianqian Yin Wei Li Zhenpeng Li Desheng Kong

Abstract Interindividual heterogeneity in the disease progression of HIV-1-infected patients receiving long-term antiretroviral therapy suggests that some host-related factors may have limited treatment efficacy. To understand the nature of factors contributing to treatment failure, we performed a retrospective cohort study of 45 chronically HIV-1-infected individuals sharing a similar demographics and route of infection, compared the differences between virologically suppressed (VS) and treatment failure (TF) patients with respect to clinical, immunological and virological characteristics. We found that the baseline diversity of HIV-1 env quasispecies was the major difference between VS and TF group, and higher baseline diversity in TF patients. We further predicted TF-related env mutations using a selection pressure-based approach, followed by an analysis of these mutations based on the available three-dimensional structures of gp120/gp41 or their complexes with neutralizing antibodies. Notably, almost all of the identified residues could be mapped to the epitopes of known HIV-1 neutralizing antibodies, especially the epitopes of broadly neutralizing antibodies, and these mutations tended to compromise antibody-antigen interactions. These results indicate that the escape of HIV-1 from host humoral immunity may play a direct role in TF in long-term antiretroviral-experienced patients and that based on env gene sequence of the viruses in the patients.

Viral quasispecies

Humoral immunity

10.1038/s41598-017-05594-5

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Citations (8)

Broader HIV-1 neutralizing antibody responses induced by envelope glycoprotein mutants based on the EIAV attenuated vaccine

Retrovirology (2010)

Lianxing Liu Yanmin Wan Lan Wu Jianping Sun Huiguang Li

Abstract Background In order to induce a potent and cross-reactive neutralizing antibody (nAb), an effective envelope immunogen is crucial for many viral vaccines, including the vaccine for the human immunodeficiency virus (HIV). The Chinese equine infectious anemia virus (EIAV) attenuated vaccine has controlled the epidemic of this virus after its vaccination in over 70 million equine animals during the last 3 decades in China. Data from our past studies demonstrate that the Env protein of this vaccine plays a pivotal role in protecting horses from both homologous and heterogeneous EIAV challenges. Therefore, the amino acid sequence information from the Chinese EIAV attenuated vaccine, in comparison with the parental wild-type EIAV strains, was applied to modify the corresponding region of the envelope glycoprotein of HIV-1 CN54. The direction of the mutations was made towards the amino acids conserved in the two EIAV vaccine strains, distinguishing them from the two wild-type strains. The purpose of the modification was to enhance the immunogenicity of the HIV Env. Results The induced nAb by the modified HIV Env neutralized HIV-1 B and B'/C viruses at the highest titer of 1:270. Further studies showed that a single amino acid change in the C1 region accounts for the substantial enhancement in induction of anti-HIV-1 neutralizing antibodies. Conclusions This study shows that an HIV envelope modified by the information of another lentivirus vaccine induces effective broadly neutralizing antibodies. A single amino acid mutation was found to increase the immunogenicity of the HIV Env.

Equine infectious anemia

HIV vaccine

Immunogen

10.1186/1742-4690-7-71

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Citations (18)

Design, synthesis and biological evaluation of ( E )-3,4-dihydroxystyryl 4-acylaminophenethyl sulfone, sulfoxide derivatives as dual inhibitors of HIV-1 CCR5 and integrase

Bioorganic & Medicinal Chemistry (2016)

Yixing Sun Weisi Xu Ningning Fan Xuefeng Sun Xianling Ning

Sulfone

Sulfoxide

Integrase inhibitor

Docking (animal)

Chemokine receptor CCR5

10.1016/j.bmc.2016.12.035

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Identification of a Novel CRF01_AE/CRF07_BC Recombinant Form in Men Who Have Sex with Men in Sichuan, China

AIDS Research and Human Retroviruses (2016)

Yan Wang Huamian Wei Weisi Xu Qianqian Yin Yi Feng

A novel second-generation CCR5-tropic HIV-1 recombinant virus (XC2014EU09) was identified here, which was isolated from a HIV-positive man who had sex with men (MSM) in Sichuan, China. Phylogenic analyses showed that XC2014EU09 was composed of two well-established circulating recombinant forms (CRF01_AE and CRF07_BC). Different from the other four reported CRF01_AE/CRF07_BC recombinant forms, three recombinant breakpoints of XC2014EU09 with four fragments were observed in the vpr, env, and nef genes, respectively, as follows: ICRF01_AE (636-5,843 nt), IICRF07_BC (5,844-8,393 nt), IIICRF01_AE (8,394-9,119 nt), and IVCRF07_BC (9,120-9,600 nt). The emergence of CRF01_AE/CRF07_BC recombinant strain indicates the increasing complexity of the HIV-1 epidemic among the MSM group in China.

Strain (injury)

10.1089/aid.2015.0276

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Profiling the neutralizing antibody response in chronically HIV-1 CRF07_BC-infected intravenous drug users naïve to antiretroviral therapy

Scientific Reports (2017)

Xintao Hu Yuanyuan Hu Chunhong Zhao Hongmei Gao Kelli Greene

Abstract Characterizing neutralizing antibody (NAb) responses in individuals infected with diverse HIV-1 strains is necessary to reveal the novel targets for regional preventive and therapeutic strategies development. We evaluated the prevalence, breadth, and potency of NAb responses in 98 CRF07_BC-infected individuals using a large, multi-subtype panel of 30 tier 2-3 Env-pseudotyped viruses. Furthermore, we compared the neutralization pattern of CRF07_BC-infected people with that of subtype B’-infected individuals in China. Of the 98 plasma samples tested, 18% neutralized more than 80% of viruses in the panel, and 53% neutralized more than 50%, suggesting the presence of broadly NAbs in these individuals. A preferential intra-subtype neutralization of CRF07_BC was found. Notably, CRF07_BC-infected individuals generated higher neutralization titers against intra-subtype viruses than subtype B’-infected individuals with longer infection length. However, subtype B’-infected individuals mounted broader neutralization responses against inter-subtype viruses than CRF07_BC infection with shorter infection time, indicating the transition from narrow autologous to broad heterologous neutralization over time. Neutralization activity of the top six plasmas from each cohort was attributable to IgG fraction, and half of them developed CD4 binding site antibody reactivity. Heatmap analysis identified three statistically robust clusters of plasmas that offer valuable resources for further in-depth virological and immunological study.

Heterologous

Intravenous drug

10.1038/srep46308

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Citations (7)

Genetic structure of Tibetan populations in Gansu revealed by forensic STR loci

Scientific Reports (2017)

Hongbing Yao Chuan‐Chao Wang Jiang Wang Xiaolan Tao Lei Shang

Abstract The origin and diversification of Sino-Tibetan speaking populations have been long-standing hot debates. However, the limited genetic information of Tibetan populations keeps this topic far from clear. In the present study, we genotyped 15 forensic autosomal short tandem repeats (STRs) from 803 unrelated Tibetan individuals from Gansu Province (635 from Gannan and 168 from Tianzhu) in northwest China. We combined these data with published dataset to infer a detailed population affinities and genetic substructure of Sino-Tibetan populations. Our results revealed Tibetan populations in Gannan and Tianzhu are genetically very similar with Tibetans from other regions. The Tibetans in Tianzhu have received more genetic influence from surrounding lowland populations. The genetic structure of Sino-Tibetan populations was strongly correlated with linguistic affiliations. Although the among-population variances are relatively small, the genetic components for Tibetan, Lolo-Burmese, and Han Chinese were quite distinctive, especially for the Deng, Nu, and Derung of Lolo-Burmese. Han Chinese but not Tibetans are suggested to share substantial genetic component with southern natives, such as Tai-Kadai and Hmong-Mien speaking populations, and with other lowland East Asian populations, which implies there might be extensive gene flow between those lowland groups and Han Chinese after Han Chinese were separated from Tibetans. The dataset generated in present study is also valuable for forensic identification and paternity tests in China.

Genetic relationship

Genetic data

10.1038/srep41195

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Citations (18)

Prevalence and Seroincidence of Hepatitis B and Hepatitis C Infection in High Risk People Who Inject Drugs in China and Thailand

Hepatitis Research and Treatment (2014)

J. Brooks Jackson Wei Liu Liping Fu Apinun Aramrattana David D. Celentano

We determined the prevalence and incidence of HBV and HCV infection in people who inject drugs (PWIDs) at high risk for HIV in China and Thailand and determined the association of HBV and HCV incidence with urine opiate test results and with short-term versus long-term buprenorphine-naloxone (B-N) treatment use in a randomized clinical trial (HPTN 058). 13.8% of 1049 PWIDs in China and 13.9% of 201 PWIDs in Thailand were HBsAg positive at baseline. Among HBsAg negative participants, the HBsAg incidence rate was 2.7/100 person years in China and 0/100 person years in Thailand. 81.9% of 1049 PWIDs in China and 59.7% of 201 in Thailand were HCV antibody positive at baseline. The HCV confirmed seroincidence rate among HCV antibody negative PWIDs was 22/100 person years in China and 4.6/100 person years in Thailand. Incident HBsAg was not significantly different in the short-term versus long-term B-N arm in China or Thailand. Participants with positive opiate results in at least 75% of their urines during the time period were at increased risk of incident HBsAg (HR = 5.22; 95% CI, 1.08 to 25.22; P=0.04) in China, but not incident HCV conversion in China or Thailand.

10.1155/2014/296958

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Deglycosylation or Partial Removal of HIV-1 CN54 gp140 V1/V2 Domain Enhances Env-Specific T Cells

AIDS Research and Human Retroviruses (2009)

Yanmin Wan Lianxing Liu Lan Wu Xianggang Huang Liying Ma

It remains a great challenge to develop an effective HIV vaccine against the most prevalent HIV-1 clade, B′/C recombinant, in China. Our objective was to test the influence of a new modification of the V1/V2 loops of HIV-1CN54 gp140 on the immunogenicity of Env. HIV-1CN54 gp140 was deglycosylated by replacing all six N residues in V1/V2 loops with six Q residues (gp140dG) or partially deleted on V1/V2 loops (gp140dV). gp140, gp140dG, and gp140dV were transferred into plasmid vector and recombinant Tiantan vaccinia (rTTV) vector to generate three DNA vaccines and three rTTV vaccines for vaccination of female BALB/c mice in a prime–boost regimen. An Elispot assay was used to read out the T cell immunity and ELISA and a poly-l-leucine (PLL) ELISA was employed to assess humoral immune responses. Surprisingly, gp140dV (1570 ± 1569 SFCs/106 splenocytes) and gp140dG (731 ± 471 SFCs/106 splenocytes) could elicit significantly higher Env-specific T cells than gp140 (224 ± 140 SFCs/106 splenocytes). Three T cell epitopes were newly identified in BALB/c mice at the N terminus of C1, C terminus of C4, and N terminus of HR, respectively. Env-specific binding antibodies and linear antibodies elicited by gp140 tended to be higher than that stimulated by gp140dG and gp140dV but did not reach statistical difference. Our data demonstrated that the deglycosylation and partial deletion of V1/V2 loops of B′/C recombinant gp140 could lead to improvement of specific T cell immune responses.

ELISPOT

V3 loop

HIV vaccine

10.1089/aid.2008.0289

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Citations (9)

Remarks On The Russian Revolution And Chinese Reform

青海师专学报 (2002)

Liying Ma

While leading the Russian Revolution,Lenin abided by the scientific attitude of seeking the truth out of factsand kept the basic principles of Marxism according to Russian's realities,and succeeded in the Russian Revolution,In china's reform,Deng Xiao-ping adopted scientific Lenin's basic ideas and method. He proceeded from china's situations instead of simply following the books or other countries experience mechanically and found out way of socialist construction.We need And we also should keep sing the truth out of factsto conduct our practical work.Thus we can open a new road of building the socialism.

Russian revolution

Cultural Revolution

Scientific socialism

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Morphologically Virus‐Like Fullerenol Nanoparticles Act as the Dual‐Functional Nanoadjuvant for HIV‐1 Vaccine

Advanced Materials (2013)

Ligeng Xu Ye Liu Zhiyun Chen Wei Li Ying Liu

Fullerenol, which self-assembles into virus-sized nanoparticles, is designed as a dual-functional nanoadjuvant to generate comparable immune responses to the HIV DNA vaccine. It shows promising adjuvant activity via various immunization routes, decreasing the antigen dosage and immunization frequency while maintaining immunity levels and inducing TEM-biased immunity to combat the infection at early stage. The underlying mechanisms by which fullerenol-based formulation induces above-mentioned polyvalent immune responses are involved in activating multiple TLRs signaling pathways. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

10.1002/adma.201300583

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Citations (131)