国产HIV病毒研究成果(Pubmed)
本帖最后由 marine0425030 于 2015-5-6 18:02 编辑在以前论坛也做过几期，反正周末也看看PUBMED就随便整理了国内的HIV研究。
我想一方面便于研究人员掌握国内HIV研究动向，另外一方面也便于考研考博的同学们找到自己感兴趣的实验室。国际方面的大文章基本会在各个板块的科研前沿上有所报道。
我是采用回复方式发表的，主要是分开发便于大家在底下写回复，便于讨论。
希望大家多多支持。。
今天多云，实验室没人，听着轻音乐，看着文献，还是蛮好的。
CH0001
J Acquir Immune Defic Syndr. 2015 Apr 15;68(5):502-10. doi: 10.1097/QAI.0000000000000530.
Simian immunodeficiency virus infection evades vaccine-elicited antibody responses to v2 region.
Guo J1, Zuo T, Cheng L, Wu X, Tang J, Sun C, Feng L, Chen L, Zhang L, Chen Z.
Author information
[*]1*AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, Research Center for Infection and Immunity, The University of Hong Kong, Hong Kong, China; †Comprehensive AIDS Research Center and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing, China; and §State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Abstract
OBJECTIVES:An effective AIDS vaccine should elicit protective antibody responses against HIV/simian immunodeficiency virus (SIV) infection. We recently reported that mucosal priming with a replicating modified vaccinia Tiantan virus (MVTTgpe)-based vaccine regimen induces durable protection against pathogenic SIVmac239 infection in rhesus monkeys. Here, we aim to conduct a comprehensive analysis on antigenic determinants recognized by specific antibody responses generated by vaccination and SIVmac239 infection.METHODS:A novel yeast surface displayed antigen library of entire SIVmac239 envelope (Env) glycoprotein was established and validated to map the major antigenic determinants (MAD) in monkey sera elicited by vaccination and infection. MAD-directed antibody responses were further analyzed for correlation of protection.
RESULTS AND CONCLUSIONS:The yeast surface displayed library allows the mapping of SIV-specific linear and conformational MAD. The MVTTgpe-based regimen induces antibodies targeting mainly to 6 antigenic domains covering the entire gp160. Critically, this regimen induced a uniquely predominant antibody response against a distinct MAD in variable region 2 (V2) as compared with the Ad5gpe-based vaccine and SIVmac239 infection. This MAD was associated with a higher titer of anti-V2 antibody responses, which was inversely correlated with peak and set-point viral loads. Unexpectedly, the pathogenic SIVmac239 challenge evaded the vaccine-elicited anti-V2 antibody response. Instead of recalling B-cell memory responses to the V2 MAD, viral infection directed anti-V1V2 antibodies primarily to V1 region. Moreover, the anti-V1V2 antibody responses diminished significantly in infected macaques after they enter the stage of simian AIDS. Our findings have critical implications to AIDS vaccine efforts with focus on V2 region.
PMID: 25622057
本帖最后由 marine0425030 于 2015-4-19 16:47 编辑
J Immunol. 2015 Apr 15;194(8):3873-82. doi: 10.4049/jimmunol.1402176. Epub 2015 Mar 16.
The Upregulation of LAG-3 on T Cells Defines a Subpopulation with Functional Exhaustion and Correlates with Disease Progression in HIV-Infected Subjects.
Tian X1, Zhang A1, Qiu C1, Wang W2, Yang Y, Qiu C1, Liu A1, Zhu L1, Yuan S1, Hu H1, Wang W1, Wei Q2, Zhang X3, Xu J3.
Author information
[*]1.Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Fudan University, Shanghai 201508, China;
[*]2.Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100021, China; and.
[*]3.Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Fudan University, Shanghai 201508, China; State Key Laboratory for Infectious Disease Prevention and Control, Chinese Center for Disease Control and Prevention, Beijing 102206, China xujianqing2014@126.com zhangxiaoyan@shaphc.org.
Abstract
T cells develop functional defects during HIV-1 infection, partially due to the upregulation of inhibitory receptors such as programmed death-1 (PD-1) and CTLA-4. However, the role of lymphocyte activation gene-3 (LAG-3; CD223), also known as an inhibitory receptor, in HIV infection remains to be determined. In this study, we revealed that LAG-3 on T cells delivers an inhibitory signal to downregulate T cell functionality, thereby playing an immunoregulatory role during persistent HIV-1 infection. We observed that HIV-1 infection results in a significant increase in LAG-3 expression in both the peripheral blood and the lymph nodes. The upregulation of LAG-3 is dramatically manifested on both CD4(+) and CD8(+) T cells and is correlated with disease progression. As expected, prolonged antiretroviral therapy reduces the expression of LAG-3 on both CD4(+) and CD8(+) T cells. The ex vivo blockade of LAG-3 significantly augments HIV-specific CD4(+) and CD8(+) T cell responses, whereas the overexpression of LAG-3 in T cells or the stimulation of LAG-3 on T cells leads to the reduction of T cell responses. Furthermore, most LAG-3 and PD-1 are expressed in different T cell subsets. Taken together, these data demonstrate that the LAG-3/MHC class II pathway plays an immunoregulatory role, thereby providing an important target for enhancing immune reconstitution in HIV-infected patients. Additionally, the LAG-3/MHC class II pathway may synergize with PD-1/PD ligand to enhance T cell-mediated immune responses.
PMID: 25780040
该研究非常完整，主要围绕以下几个问题来阐述CD233在HIV感染中的作用。
1. HIV感染后LAG-3的表达变化和疾病的关联
2.HARRT治疗对LAG-3在细胞表面表达的影响
3. 通过用抗体block试验来测试T细胞活性是否可以得到改变。
本帖最后由 marine0425030 于 2015-4-19 16:59 编辑
Vaccine. 2015 Apr 15;33(16):1974-80. doi: 10.1016/j.vaccine.2015.02.053. Epub 2015 Feb 28.
A truncated fragment of Ov-ASP-1 consisting of the core pathogenesis-related-1 (PR-1) domain maintains adjuvanticity as the full-length protein.
[*]Jingjing Guoa, 1,Yi Yanga, 1,Wenjun Xiaoa, 1,Weilai Suna,Hong Yua,Lanying Dub,Sara Lustigmanb,Shibo Jiangb, c,Zhihua Koua, Yusen Zhoua
Highlights
[*]Ov-ASP-1, an onchocerca volvulus protein, has good adjuvanticity for protein antigens.
[*]A truncated Ov-ASP-1 (ASPPR) maintains adjuvanticity as the full-length of Ov-ASP-1.
[*]ASPPR augments humoral and cellular immune responses elicited by protein antigens.
[*]ASPPR has potential to be further developed as a novel adjuvant for human use.
AbstractThe Onchocerca volvulus activation-associated secreted protein-1 (Ov-ASP-1) has good adjuvanticity for a variety of antigens and vaccines, probably due to its ability activate antigen-processing cells (APCs). However, the functional domain of Ov-ASP-1 as an adjuvant is not clearly defined. Based on the structural prediction of this protein family, we constructed a 16-kDa recombinant protein of Ov-ASP-1 that contains only the core pathogenesis-related-1 (PR-1) domain (residues 10–153), designated ASPPR. We found that ASPPR exhibits adjuvanticity similar to that of the full-length Ov-ASP-1 (residues 10–220) for various antigens, including ovalbumin (OVA), HBsAg protein antigen, and the HIV peptide 5 (Pep5) antigen, but it is more suitable for vaccine design in ASPPR-antigen fusion proteins, and more stable in PBS than Ov-ASP-1 stored at −70 °C. These results suggest that ASPPR might be the functional region of Ov-ASP-1 as an adjuvant, and therefore could be developed as an adjuvant for human use.
PMID: 25736195
PS：这个蛋白佐剂作用机制
Ov-ASP-1 was shown to bind specifically to human antigen presenting cells (APCs) and to trigger Th1-biased proinflammatory cytokine production in naïve PBMCs, most likely through its ability to activate monocyte-derived dendritic cells, TLR2 and TLR4 .
BMC Public Health. 2015 Apr 11;15(1):362.
Prevalence of human immunodeficiency virus 1 infection in the last decade among entry travelers in Yunnan Province, China.Wang B1, Liang Y2, Feng Y3, Li Y4, Wang Y5, Zhang AM6, Baloch Z7, Liu L8, Qin W9, Xia X10.
[*]1.Faculty of Environmental Science and Engineering & Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China. binghuiwang@aliyun.com.
[*]2Care Center for International Travel Health in Yunnan, Kunming, China. ynkmlyb@163.com.
Abstract
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.
PMID: 25886406
PS：非常有意义的分析
本帖最后由 marine0425030 于 2015-4-19 17:15 编辑
J Med Virol. 2015 Apr 10. doi: 10.1002/jmv.24202.
HIV-1 prevalence and subtype/recombinant distribution among travelers entering China from Vietnam at the HeKou port in the Yunnan province, China, between 2003 and 2012.
Wang Y1, Liang Y, Feng Y, Wang B, Li Y, Wu Z, Zhang J, Baloch Z, Zhang AM, Liu L, Qin W, Xia X.
Author information
Faculty of Life Science and Technology, Center for Molecular Medicine in Yunnan province, Kunming University of Science and Technology, Yunnan, China.
AbstractThe 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.
KEYWORDS:human immunodeficiency virus; molecular epidemiology; subtype distribution
PMID: 25865741
PS: 该研究小组用了上贴一样的数据，该研究对病毒亚型分布做了初步的研究。
本帖最后由 marine0425030 于 2015-4-19 17:30 编辑
Int J Pharm. 2015 Apr 10;483(1-2):188-99. doi: 10.1016/j.ijpharm.2015.02.021. Epub 2015 Feb 11.
Zirconium phosphatidylcholine-based nanocapsules as an in vivo degradable drug delivery system of MAP30, a momordica anti-HIV protein.
Caizhen G1, Yan G2, Ronron C2, Lirong Y3, Panpan C1, Xuemei H4, Yuanbiao Q5, Qingshan L6.
Author information
[*]1Department of Bioscience, Luliang University, Shanxi 033001, PR China.
[*]2School of Pharmaceutical Sciences, Shanxi Medical University, Shanxi 030001, PR China.
[*]3Department of Chemical and Biological Engineering, Zhejiang University, Zhejiang 310027, PR China.
[*]4Department of Chemistry and Chemical Engineering, Luliang University, Shanxi 033001, PR China.
[*]5Graduate Institute of Pharmaceutical Chemistry, Luliang University, Shanxi 033001, PR China. Electronic address: qyb_0222@sina.com.
[*]6School of Pharmaceutical Sciences, Shanxi Medical University, Shanxi 030001, PR China. Electronic address: sxlqs2012@163.com.
AbstractAn essential in vivo drug delivery system of a momordica anti-HIV protein, MAP30, was developed through encapsulating in chemically synthesized matrices of zirconium egg- and soy-phosphatidylcholines, abbreviated to Zr/EPC and Zr/SPC, respectively. Matrices were characterized by transmission electron microscopy and powder X-ray diffractometry studies. Zr/EPC granule at an approximate diameter of 69.43±7.78nm was a less efficient encapsulator than the granule of Zr/SPC. Interlayer spacing of the matrices encapsulating MAP30 increased from 8.8 and 9.7Å to 7.4 and 7.9nm, respectively. 结构大小比较In vivo kinetics on degradation and protein release was performed by analyzing the serum sampling of intravenously injected SPF chickens. The first order and biphasic variations were obtained for in vivo kinetics using equilibrium dialysis. 体内动力学Antimicrobial and anti-HIV assays yielded greatly decreased MIC50 and EC50 values of nanoformulated MAP30. An acute toxicity of MAP30 encapsulated in Zr/EPC occurred at a single intravenous dose above 14.24mg/kg bw in NIH/KM/ICR mice. 抗病毒抗病原效果The folding of MAP30 from Zr/EPC sustained in vivo chickens for more than 8 days in high performance liquid chromatography assays. 体内动力学 These matrices could protect MAP30 efficiently with strong structure retention, lowered toxicity and prolonged in vivo life.
KEYWORDS:
In vivo degradation and release; Nanoencapsulation; Protein structure stability; Therapeutic anti-HIV protein; Zirconium phosphatidylcholine
PMID: 25681721
本文主要讲的是开发了两种可以输送抗HIV病毒蛋白MAP30的载体。
Jpn J Infect Dis. 2015 Apr 10.
Development of a multiplex real-time PCR assay for the detection of Treponema pallidum, HCV, HIV-1 and HBV.Zhou L1, Gong R, Lu X, Zhang Y, Tang J.
Author information
[*]1Hubei Collaborative Innovation Center for Industrial Fermentation, Hubei University of Technology.
AbstractT. pallidum, HCV, HIV-1 and HBV are major causes of sexually transmitted diseases through the blood. A sensitive and efficient method for detection is critical for early diagnosis and for large-scale screening of denoted blood specimens in China. This study aims to establish an assay to detect these pathogens in clinical serum specimens. We established a TaqMan-LNA real-time PCR assay for rapid, sensitive, specific, quantitative, and simultaneous detection and identification. The copy numbers of standards of these four pathogens were quantified. Standard curves were generated by determining the mean cycle threshold (Ct) values versus 10-fold serial dilutions of standards over a range of 106 to 101 copies / μL with the lowest detection limit of the assay at 101 copies / μL. The assay was applied for 328 clinical specimens, and compared with ELISA and commercial NAT method. The assay identified 39 T. pallidum-, 96 HCV-, 13 HIV-1-, 123 HBV-, 5 HBV/HCV-, 1 T. pallidum/HBV-,1 HIV-1/HCV-, 1 HIV-1/T. pallidum- positive specimens. By showing greater sensitivity, this assay becomes a highly reliable, cost-effective and useful molecular diagnostic tool for large-scale screening of clinical specimens and will assist in the study of the pathogenesis and epidemiology of sexually transmitted blood diseases.
PMID: 25866106
该文主要是建立了一个对T. pallidum, HCV, HIV-1 and HBV更快更敏感的检测方法。
Lancet. 2015 Apr 18;385(9977):1510. doi: 10.1016/S0140-6736(15)60753-X.
HIV incidence and mortality in China.Jia Z1, Ruan Y2, Lu Z3.
Author information
[*]1National Institute of Drug Dependence and Peking University Clinical Research Institute, Peking University, Beijing, China.
[*]2State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing 102206, China. Electronic address: ruanyuhua92@gmail.com.
[*]3Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, China.
We read with interest, the Global Burden of Disease Study (GBD) by Christopher Murray and colleagues reporting global, regional, and national estimates of HIV/AIDS incidence and mortality for 1990–2013, which included an estimate of 35 665 new HIV cases and 12 145 deaths in China in 2013. This number of deaths is almost a third lower than the 19 716 deaths reported for the same year by the National Center for AIDS/STD Control and Prevention (NCAIDS) within the Chinese Center For Disease Control and Prevention (CDC). The related estimate of HIV incidence reported by Murray and colleagues is also lower than the 90 119 cases reported by the CDC, although whether these CDC cases were new infections in 2013 could not be confirmed. The GBD 2013 estimates were clearly flawed because they were dependent on mortality data from the Chinese Notifiable Infectious Disease Reporting System, which records mortality only for HIV-positive individuals with AIDS, and does not report the number of deaths in HIV-positive individuals without AIDS.In response to the worldwide threat of infectious disease, China has developed several specific systems for monitoring major communicable diseases, including HIV and tuberculosis. These systems include the special National HIV/AIDS Reported System, managed by NCAIDS. Gaps in the coverage of these reporting systems are clear. However, in the past few years plans to improve them have been scheduled,and the government's response to the HIV epidemic is based on data (including incidence and mortality) from these reporting systems. The Ministry of Health in China, UNAIDS, and WHO have all shown confidence in these systems' data integrity by using them for estimates of the HIV/AIDS epidemic in China, including the UNAIDS spectrum model.All estimates are uncertain, and national estimates of incidence and mortality that are based on reported cases are almost always lower than the true value. We do not argue that a consistent and comprehensive approach for HIV control and prevention could be as powerful for China as it has proven for Africa. However, we feel it is important to clarify that the reported (not estimated) number of HIV-related deaths in China was a third higher than that estimated by Murray and colleagues' analysis.We declare no competing interests.
AIDS Patient Care STDS. 2015 Apr 30.
Shifting Patterns of the HIV Epidemic in Southwest China: A Case Study Based on Sentinel Surveillance, 1995-2012.
Chow EP1, Gao L, Chen L, Jing J, Zhang L.
Author information
Research Center for Public Health, School of Medicine, Tsinghua University , Beijing, China .
AbstractThe HIV epidemic is experiencing a rapid shift in transmission profile in China. This study aims to examine the changes in magnitude, transmission pattern, and trend of the HIV epidemic in a typical Southwest Chinese prefecture over the period of 1995-2012. HIV surveillance data from the web-based reporting system were analyzed during this period. We investigated the temporal trends in the changing characteristics of HIVtransmission, the HIV disease burden in key affected populations, and assessed the impacts on HIV disease progression due to scale-up of antiretroviral treatment. A total of 3556 HIV/AIDS cases were reported in Yuxi prefecture, Yunnan, over the study period. The number of HIV tests conducted has dramatically increased from 1041 in 1995 to 247,859 in 2012, resulting in a substantial increase in HIV diagnoses from 11 cases to 327 cases over the same period. Since 2005, cumulatively 1250 eligible people living with HIV (PLHIV) have received combination antiretroviral therapy which reduced AIDS disease progression from 9.0% (95% CI: 6.7-11.4%) in 1995 to 0.1% (0-0.3%) in 2012 (ptrend=0.0002). The primary mode of HIV transmission has been shifted from injection sharing (71.9% diagnoses in 1995-2004) to unsafe sexual contacts (82.6% diagnoses in 2012). Yuxi prefecture is experiencing a concentrated but shifting HIV epidemic. Scale-up of HIV testing is essential to effective sentinel surveillance and enhancing early diagnosis and treatment in PLHIV.
PMID: 25928866
听过第一篇文章的内容，张教授讲确定强抗原的位点有助于提高检测试剂的灵敏度。
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