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Antiviral Activity of Dual-acting Hydrocarbon-stapled Peptides against HIV-1 Predominantly Circulating in China

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Biomedical and Environmental Sciences 2017年第6期30卷 398-406页

作者： WANG Yan CURRELI Francesca XU Wei Si LI Zhen Peng KONG De Sheng REN Li HONG Kun Xue JIANG Shi Bo SHAO Yi Ming DEBNATH Asim K MA Li Ying State Key Laboratory of Infectious Disease prevention and Control National Center for AIDS/STD Control and PreventionCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesChinese Center for Disease Control and PreventionBeijing 102206China State Key Laboratory of Infectious Disease prevention and Control National Institute for Communicable Disease Control and PreventionCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesChinese Center for Disease Control and PreventionBeuhing 102206China Laboratory of Molecular Modeling and Drug Design Lindsley F.Kimball Research Institute of the New York Blood CenterNew York 10065USA Key Laboratory of Medical Molecular Virology of Ministries of Education and Health Shanghai Medical College and Institute of Medical MicrobiologyFudan UniversityShanghai 200032China

Objective New rationally designed i,i＋7-hydrocarbon-stapled peptides that target both HIV-1 assembly and entry have been shown to have antiviral activity against HIV-1 subtypes circulating in Europe and North America. Here, we aimed to evaluate the antiviral activity of these peptides against HIV-1 subtypes predominantly circulating in China. Methods The antiviral activity of three i,i＋7-hydrocarbon-stapled peptides, NYAD-36, NYAD-67, and NYAD-66, against primary HIV-1 CRF07_BC and CRFOI_AE isolates was evaluated in peripheral blood mononuclear cells （PI3MCs）. The activity against the CRF07_BC and CRF01_AE Env-pseudotyped viruses was analyzed in TZM-bl cells. Results We found that all the stapled peptides were effective in inhibiting infection by all the primary HIV-1 isolates tested, with 50% inhibitory concentration toward viral replication （ICso） in the low micromolar range. NYAD-36 and NYAD-67 showed better antiviral activity than NYAD-66 did. We further evaluated the sensitivity of CRF01_AE and CRF07_BC Env-pseudotyped viruses to these stapled peptides in a single-cycle virus infectivity assay. As observed with the primary isolates, the ICs0s were in the low micromolar range, and NYAD-66 was less effective than NYAD-36 and NYAD-67. Conclusion Hydrocarbon-stapled peptides appear to have broad antiviral activity against the predominant HIV-1 viruses in China. This finding may provide the impetus to the rational design of peptides for future antiviral therapy.

关键词： Hydrocarbon-stapled peptide HIV-1 CRF07 BC CRFOI_AE Antiviral activity

aids Research and Its Role in China's aids prevention and Control Policies

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Virologica Sinica 2007年第6期22卷 421-425页

作者： Yi-ming SHAO State Key Laboratory for Infectious Diseases prevention and Control National Center for AIDS / STD Control and Prevention Chinese Center for Disease Control and Prevention Beijing 100050 China

By the end of 2005,the estimated number of HIV infected people in China was 650,000. The seriousness of the epidemic calls for effective control measures to tackle the problems in order to avoid the tragedy in Africa from happening in China. "prevention First" is the cornerstone of the country's health policy. On 2003 World aids Day,Premier Jiabao Wen announced a new national aids control policy,"Four Frees and One Care". This policy clearly shows that the chinese government has once again taken full responsibility to solve public health problems and has profound impact far beyond the aids field. In early 2006,the central government put scientific and technology innovation as a national priority and set the target to build an innovative China by year 2020. Since then,the government has been increasing investment in science and technology with major emphasis on both infectious diseases control and new drug research and development. For the first time,development of 100 new drugs and control of major infectious diseases (aids,HBV,TB and other emerging infectious diseases) have been selected as national key scientific projects. China's best minds in related fields will be pooled to work together in order to remove the technical barriers blocking efficient control of the major infectious disease in China. Knowledge on molecular epidemiology,immunology,pathogenesis,HAART,as well as HIVDR strains will certainly provide urgently needed scientific information for China's aids control program. Only evidence-based strategy from good research will provide long-term effective control of aids.

关键词： aids prevention Control

Human immunodeficiency virus prevention strategies in China

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chinese Medical Journal 2020年第3期133卷 318-325页

作者： Zun-You Wu Sarah Robbins Scott Division of HIV prevention National Center for AIDS/STD Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China Department of Epidemiology Fielding School of Public HealthUniversity of CaliforniaLos AngelesCAUnited States.

This paper reviews the current epidemics of human immunodeficiency virus(HIV)infection in China,particularly the globally available prevention strategies developed and *** review focuses on HIV prevention measures in general,such as education,testing,and counseling and in specific responses to transmission modes,such as blood safety,harm reduction for people who inject drugs,and condom promotion to reduce sexual *** also assess newly developed prevention measures,such as prevention treatment,pre-exposure prophylaxis,post-exposure prophylaxis,male circumcision,and promising potential future preventions,including microbicides and *** on this assessment,we provide recommendations for their implementation in *** conclude that there is no magic bullet for HIV prevention,particularly sexual transmission of the disease,but only a combination of these prevention strategies can control the HIV epidemic.

关键词： Human immunodeficiency virus infection Epidemic prevention strategies China

Factors associated with unprotected anal intercourse among male students who have sex with men in three Northern regions of China

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chinese Medical Journal 2019年第14期132卷 1639-1644页

作者： De-Chuan Zhang Zun-You Wu Sarah Robbins Scott Department of Epidemiology and Biostatistics School of Public HealthAnhui Medical UniversityHefeiAnhui 230032China National Center for aids/std Control and prevention Chinese Center for Disease Control and PreventionBeijing 102206China

Background:Unprotected anal intercourse (UAI) has previously been associated with human immunodeficiency virus (HIV) *** students who have sex with men (SMSM) are at increased exposure to experience *** aim of this study was to investigate the status of UAI and related factors among SMSM in three northern regions of ***:From November 2018 to January 2019,SMSM,18 years or older,studying or living in Beijing,Tianjin,or Shijiazhuang,who had anal sex in the past 6 months were recruited by community-based organizations to participate in an unmatched,casecontrol *** demographic and behavioral information were collected via self-administrated electronic questionnaires and factors related to UAI were assessed using uni-and multivariate logistic regression ***:Among the 511 SMSM included in the study,210 (41.1%) reported UAI in the past 6 *** who had sexual partners at least 10 years older than themselves (odds ratio [OR]=2.277,95% confidence interval [CI]:1.380-3.756),used vacant capsules before sexual activity (OR =3.858,95 % CI:1.472-10.106),had a self-perceived moderate-HIV risk (OR =2.128,95 %CI:1.403-3.227),and unprotected,first anal intercourse (OR =2.236,95 % CI:1.506-3.320) had increased odds of ***:Factors associated with increased odds of engaging in UAI in the past 6 months among SMSM included having older sexual partners,using vacant capsules,having a self-perceived moderate risk of HIV,and unprotected,first anal *** education on risk reduction,including improving condom decision making in age-discordant relationships could help address the sexual risk behaviors among SMSM.

关键词： Students Men who have sex with men Unsafe Sex China

Asymptomatic and Pre-Symptomatic COVID-19 in China

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Infectious Diseases of Poverty 2020年第3期9卷 1-2页

作者： Zunyou Wu Jennifer M.McGoogan National Center for aids/std Control and prevention Chinese Center for Disease Control and Prevention155 Changbai RoadChangping DistrictBeijing 102206China

As the novel coronavirus disease 2019(COVID-19)pandemic spreads rapidly across the globe many unanswered questions about the basic biology and epidemiology of the disease hamper our response strategies and limit our ability to achieve control and prevent a rebound or so-called“second wave”.One such crucial question is:To what degree do asymptomatic cases contribute to transmission?Early,small studies on this subject have found wide ranging estimates of the prevalence of asymptomatic carriers,and just a handful of studies so far have documented viral shedding by asymptomatic cases[1].We recently re-examined China’s COVID-19 case report data to investigate this question[2].This Editorial aims to describe how asymptomatic cases contribute to transmission and what the implications are for control strategies.

关键词： Novel coronavirus disease 2019 Asymptomatic Pre-symptomatic Transmission

Control of HIV/aids can be achieved with multi-strategies

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Global Health Journal 2019年第2期3卷 29-32页

作者： Roger Detels Jing Wu Zunyou Wu Department of Epidemiology Fielding School of Public HealthUniversity of California at Los AngelesCA 90095USA Department of Epidemiology School of Public HealthAnhui Medical UniversityHefei 230032China Division of HIV prevention National Center for AIDS/STD Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China

Over past three decades,many prevention strategies have been proven effective in reducing human immunodeficiency virus (HIV) ***,none of these strategies alone are effective to stop the spread of *** review discusses a few key prevention strategies,including testing,harm reduction,prevention,prophylaxis,and modern communication *** argue that although there are great challenges remaining to stop HIV transmission via sexual contact and injecting drug use routes,the combination of these effective strategies,control HIV epidemic can be achieved.

关键词： HIV prevention strategy Control Epidemic

China CDC’s HIV/aids Vaccine Efforts, from Basic Research to Clinical Studies

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China CDC weekly 2020年第48期2卷 929-932页

作者： Yiming Shao Ying Liu Yanling Hao Jing Xu Taisheng Li Hao Wu Tong Zhang Lihua Wu Shuhui Wang Dan Li Li Ren Yingqi Wu National Center for aids/std Control and prevention Chinese Center for Disease Control and PreventionBeijingChina National Vaccine and Serum Institute BeijingChina Peking Union Medical College Hospital BeijingChina Beijing Youan Hospital BeijingChina The First Affiliated Hospital Zhejiang University School of MedicineHangzhouZhejiangChina

After nearly 40 years of research and control efforts,much progress has been made to accomplish the most significant achievements in antiviral drug development and cocktail therapy that has transformed the human immunodeficiency virus/acquired immunodeficiency syndrome(HIV/aids)treatment regiment from having the highest mortality into a manageable chronic disease like hypertension or diabetes.

关键词： HIV/aids immunodeficiency hypertension

Living Conditions and Palliative Care Needs among End-of-Life Former Commercial Plasma Donors Affected with HIV/aids in Rural Henan of China

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Biomedical and Environmental Sciences 2010年第4期23卷 279-286页

作者： Yu SHENG ZE-QI QIU YUN HE NAOMI JUNIPER YAN ZHANG School of Nursing Peking Union Medical College Beijing 100144 China Center for Disease Control and prevention Zhengzhou 450016 Henan China National Center for aids/std Control and prevention Chinese Center for Disease Control and prevention Beijing 102206 China

Objective China began providing antiretroviral therapy to people living with HIV/aids （PLWHA） in 2003. This study was to investigate the living conditions, including quality of life and happiness, and need for palliative care of end-of-life PLWHA in rural Henan. Methods One hundred end-of-life aids patients were selected from Weishi, Zhenping and Tanghe counties in Henan, using convenience sampling. The World Health Organization Quality of Life for HIV （WHOQOL-HIV） BREF chinese Version was used to measure the quality of life and the Memorial University of Newfoundland Scale of Happiness （MUNSH） was employed to measure subjective welfare. Qualitative interviews and focus group discussions were undertaken to learn about the palliative care provided and the specific needs of the end-of-life patients. Results Patients’ overall quality of life was moderate （12.62±1.97）. Highest scores were in the spirituality/religion/personal beliefs, higher than the average scores in the chinese population （P0.01）, while psychological （13.58±2.06） and environment （12.50±3.28） domain scores were similar to the latter （P0.05）. Both independence （12.15±2.15） and physiological （14.04±3.16） domain scores were lower than the average of the people living with HIV/aids in other studies （P0.01）; however, all were in the moderate range. The average MUNSH score was 21.00±6.20, which was also moderate. The in-depth interviews indicated that the Henan Provincial Government’s policy of treatment and care had a beneficial impact on end-of-life aids patients, although the care components could be improved. Conclusions Living conditions of the end-of-life aids patients were moderate, and the HIV/aids palliative care model used was beneficial to them. Care could be improved by assisting the family unit as a whole.

关键词： Living conditions People living with HIV/ aids PLWHA End-of-life China Plasma donors

Duration of Human Immunodeficiency Virus Infection at Diagnosis among New Human Immunodeficiency Virus Cases in Dehong, Yunnan, China, 2008-2015

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chinese Medical Journal 2018年第16期131卷 1936-1943页

作者： Ai-Hua Li Zun-You Wu Zhen Jiang Jennifer M. McGoogan Yan Zhao Song Duan National Center for aids/std Control and prevention Chinese Center for Disease Control and Prevention Beijing 102206 China Department of Epidemiology University of California Los Angeles California USA Dehong Prefecture Center for Disease Control and prevention Mangshi Yunnan 678400 China

Background： On diagnosis of human immunodeficiency virus （HIV） infection, a person may have been infected already for many years. This study aimed to estimate the duration of HIV infection at the time of diagnosis. Methods： Newly diagnosed HIV cases in Dehong, China, from 2008 to 2015 were studied. Duration of infection at the time of diagnosis was calculated using the first CD4 cell count result after diagnosis and a CD4 depletion model of disease progression. Multiple linear regression analysis was used to investigate the associated risk factors. Results： A total of 5867 new HIV cases were enrolled. Overall, mean duration of infection was 6.3 years （95% confidence interval [CI]： 6.2, 6.5）. After adjusting for confounding, significantly shorter durations of infection were observed among participants who were female （beta： -0.37, 95% CI： -0.64, -0.09）, Dai ethnicity （beta： -0.28, 95% CI： -0.57, 0.01 ）, and infected through injecting drug use （beta： -1.82, 95% CI： -2.25, -1.39）. Compared to the hospital setting, durations were shorter for those diagnosed in any other settings, and compared to 2008, durations were shorter for those diagnosed all years after 2010. Conclusion： Although the reduction in duration of infection at the time of diagnosis observed in Dehong was significant, it may not have had a meaningful impact.

关键词： China Delayed Diagnosis Human lmmunodeficiency Virus Infection