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Cost and safety of assisted reproductive technologies for human immunodeficiency virus-1 discordant couples 被引量:1
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作者 Ming-Yih Wu Hong-Nerng Ho 《World Journal of Virology》 2015年第2期142-146,共5页
Due to significant advances in the treatment of human immunodeficiency virus type-1(HIV-1), HIV-1 infection gradually has become a treatable chronic disease. Successfully treated HIV-positive individuals can have a no... Due to significant advances in the treatment of human immunodeficiency virus type-1(HIV-1), HIV-1 infection gradually has become a treatable chronic disease. Successfully treated HIV-positive individuals can have a normal life expectancy. Hence, more and more HIV-1 discordant couples in Taiwan and the rest of the world are seeking fertility assistance. Pre-treatment of highly active antiretroviral therapy(HAART) combined with sperm washing and RT-polymerase chain reaction examination for HIV-1 viral load has become the standard procedure to assist them to conceive. However,in order to reduce the transmission risk to the lowest level for the couple and to diminish the cost of health care for the insurance institutes or government, in vitro fertilization(IVF)-intracytoplasmic sperm injection(ICSI) therapy provides the ideal solution for HIV-1 discordant couples with infected men. Intrauterine insemination(IUI) theoretically introduces more than 107 times of sperm counts or semen volume to uninfected women vs IVF-ICSI. However, since some regimens of HAART may significantly decrease the sperm motility, compared to IVF-ICSI, IUI only produces 1/5 to 1/2 pregnancy rates per cycle. Given the risk of seroconversion of HIV infection which actually happens after successful treatment, IVF-ICSI for these HIV-1 seropositive men is more cost-effective and should be the first line treatment for these cases. 展开更多
关键词 Highly active ANTIRETROVIRAL therapy human immunodeficiency virus-1 DISCORDANT SEROCONVERSION INTRAUTERINE INSEMINATION INTRACYTOPLASMIC sperm injection
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Improvement in human immunodeficiency virus-1/acquired immune deficiency syndrome patients' well-being following administration of “Phyto V7”
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作者 Ruben Wernik Jose L Priore +2 位作者 Walter F Goldman Adriana del Carmen Elias Gadi Borkow 《World Journal of Clinical Infectious Diseases》 2015年第2期44-50,共7页
AIM:To corroborate the capacity of Phyto V7,a complex of phytochemicals,to improve the physical well-being of human immunodeficiency virus-1(HIV-1) infected and acquired immune deficiency syndrome(AIDS) patients not u... AIM:To corroborate the capacity of Phyto V7,a complex of phytochemicals,to improve the physical well-being of human immunodeficiency virus-1(HIV-1) infected and acquired immune deficiency syndrome(AIDS) patients not undergoing antiretroviral treatment.METHODS:Two hundred and thirty nine HIV-1 seropositive male and female voluntary inmates were recruited through the Uruguay National Program of AIDS.The study participants received for 90 consecutive days every eight hours two tablets(760 mg/each) of Phyto V7,containing a mix of the following phytochemicals:flavonols(Kaempferol,Quercetin),flavones(Apigenin,Luteolin),hydroxycinnamic acids(ferrulic acid),carotenoids(Lutein,Lycopene,Beta carotene) and organosulfur compounds,all from vegetal origin.The participants did not receive any antiretroviral treatment during the study.At days 0,30,60 and 90(± 2 d) the participants were evaluated for body mass index(BMI),tolerance to Phyto V7 and Index of Quality of Life based on the Karfnosky scale.ANOVA,Tukey Post-test,χ2 test and Wilcoxon Signed Rank test were used to analyze the effect of treatment.RESULTS:One hundred and nighty nine study participants finished the study.Already after 30 d of Phyto V7 consumption,the weight,BMI and Karnofsky score statistically significantly improved(P < 0.001),and continued to improve until the end of the study.The mean weight gain per participant during the 90 d wasof 1.21 kg(approximately 2% of body weight).The overall increase in the mean Karnofsky score after 90 d was 14.08%.The lower the BMI and Karnofsky score of the participants were at the beginning of the study,the more notorious was the improvement over time.For example,the mean increment of Index of Quality of Life,among the participants with an initial Karnofsky score of 5 or below(n = 33) from day 0 to day 90,was of 35.67%(0.476 ± 0.044 vs 0.645 ± 0.09; P < 0.001).The tolerability to Phyto V7 was very good and no adverse reactions were recorded or reported.CONCLUSION:Administration of the Phyto V7 can be an important tool to improve the well-being of HIV-1 seropositive individuals and AIDS patients,not undergoing antiretroviral treatment. 展开更多
关键词 PHYTOCHEMICALS Karnofsky score Nutrition human immunodeficiency virus-1 ACQUIRED immune DEFICIENCY syndrome
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Impact of antiretroviral therapy on lipid metabolism of human immunodeficiency virus-infected patients: Old and new drugs 被引量:9
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作者 Joel da Cunha Luciana Morganti Ferreira Maselli +2 位作者 Ana Carolina Bassi Stern Celso Spada Sérgio Paulo Bydlowski 《World Journal of Virology》 2015年第2期56-77,共22页
For human immunodeficiency virus(HIV)-infected patients, the 1990s were marked by the introduction of highly active antiretroviral therapy(HAART) representing a new perspective of life for these patients. The use of H... For human immunodeficiency virus(HIV)-infected patients, the 1990s were marked by the introduction of highly active antiretroviral therapy(HAART) representing a new perspective of life for these patients. The use of HAART was shown to effectively suppress the replication of HIV-1 and dramatically reduce mortality and morbidity, which led to a better and longer quality of life for HIV-1-infected patients. Apart from the substantial benefits that result from the use of various HAART regimens, laboratory and clinical experience has shown that HAART can induce severe and considerable adverse effects related to metabolic complications of lipid metabolism, characterized by signs of lipodystrophy, insulin resistance, central adiposity, dyslipidemia, increased risk of cardiovascular disease and even an increased risk of atherosclerosis. New drugs are being studied, new therapeutic strategies are being implemented, and the use of statins, fibrates, and inhibitors of intestinal cholesterol absorption have been effective alternatives. Changes in diet and lifestyle have also shown satisfactory results. 展开更多
关键词 human immunodeficiency virus-1 infection Highly active antiretroviral therapy Protease inhibitors DYSLIPIDEMIA ATHEROSCLEROSIS LIPODYSTROPHY STATINS FIBRATES Diet LIFESTYLE
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Development of a droplet digital polymerase chain reaction assay for the sensitive detection of total and integrated HIV-1 DNA
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作者 Lin Yuan Zhiying Liu +13 位作者 Xin Zhang Feili Wei Shan Guo Na Guo Lifeng Liu Zhenglai Ma Yunxia Ji Rui Wang Xiaofan Lu Zhen Li Wei Xia Hao Wu Tong Zhang Bin Su 《Chinese Medical Journal》 SCIE CAS CSCD 2024年第6期729-736,共8页
Background:Total human immunodeficiency virus(HIV)DNA and integrated HIV DNA are widely used markers of HIV persistence.Droplet digital polymerase chain reaction(ddPCR)can be used for absolute quantification without n... Background:Total human immunodeficiency virus(HIV)DNA and integrated HIV DNA are widely used markers of HIV persistence.Droplet digital polymerase chain reaction(ddPCR)can be used for absolute quantification without needing a standard curve.Here,we developed duplex ddPCR assays to detect and quantify total HIV DNA and integrated HIV DNA.Methods:The limit of detection,dynamic ranges,sensitivity,and reproducibility were evaluated by plasmid constructs containing both the HIV long terminal repeat(LTR)and human CD3 gene(for total HIV DNA)and ACH-2 cells(for integrated HIV DNA).Forty-two cases on stable suppressive antiretroviral therapy(ART)were assayed in total HIV DNA and integrated HIV DNA.Correlation coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive(CD4^(+))T-cell counts,CD8^(+)T-cell counts and CD4/CD8 T-cell ratio,respectively.The assay linear dynamic range and lower limit of detection(LLOD)were also assessed.Results:The assay could detect the presence of HIV-1 copies 100%at concentrations of 6.3 copies/reaction,and the estimated LLOD of the ddPCR assay was 4.4 HIV DNA copies/reaction(95%confidence intervals[CI]:3.6-6.5 copies/reaction)with linearity over a 5-log_(10)-unit range in total HIV DNA assay.For the integrated HIV DNA assay,the LLOD was 8.0 copies/reaction(95%CI:5.8-16.6 copies/reaction)with linearity over a 3-log 10-unit range.Total HIV DNA in CD4^(+)T cells was positively associated with integrated HIV DNA(r=0.76,P<0.0001).Meanwhile,both total HIV DNA and integrated HIV DNA in CD4^(+)T cells were inversely correlated with the ratio of CD4/CD8 but positively correlated with the CD8^(+)T-cell counts.Conclusions:This ddPCR assay can quantify total HIV DNA and integrated HIV DNA efficiently with robustness and sensitivity.It can be readily adapted for measuring HIV DNA with non-B clades,and it could be beneficial for testing in clinical trials. 展开更多
关键词 human immunodeficiency virus HIV integrated HIV-1 DNA Total HIV DNA Droplet digital polymerase chain reaction HIV reservoir Antiretroviral therapy
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Alu-LTR PCR检测整合型HIV-1实验方法的优化 被引量:2
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作者 李娟 焦艳梅 +3 位作者 画伟 张彤 吴昊 高艳青 《首都医科大学学报》 CAS 北大核心 2009年第5期631-634,共4页
目的对Alu-LTRPCR检测整合型HIV-1的实验方法进行优化。方法收集20例HIV-1感染患者及10例健康对照者的抗凝血标本,纯化CD4+T细胞并提取DNA,根据整合型HIV-1DNA的特点设计引物,首轮PCR5′端引物来自于人类保守的Alu序列,3′端引物来自于H... 目的对Alu-LTRPCR检测整合型HIV-1的实验方法进行优化。方法收集20例HIV-1感染患者及10例健康对照者的抗凝血标本,纯化CD4+T细胞并提取DNA,根据整合型HIV-1DNA的特点设计引物,首轮PCR5′端引物来自于人类保守的Alu序列,3′端引物来自于HIV-1LTRU5区序列,扩增片段包含了整合位点上游的人类基因组DNA序列和整合的HIV-1LTR的序列。第二轮引物针对HIV-1LTRU3区的序列。在首轮PCR基础上,PCR产物稀释后进行第二轮PCR。结果经过优化的Alu-LTRPCR,20例HIV病人全部检测到整合的HIV-1。结论经优化后,Alu-LTRPCR检测整合型HIV-1的实验方法的灵敏度明显提高。 展开更多
关键词 Alu-PCR 整合型HIV-1 CD4+T细胞
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Alu-LTR PCR方法检测HAART治疗系列各细胞亚群的整合型HIV-1 DNA 被引量:1
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作者 李娟 焦艳梅 +3 位作者 高艳青 寇卜心 张彤 吴昊 《首都医科大学学报》 CAS 北大核心 2011年第4期449-452,共4页
目的应用Alu-LTR PCR方法对高效抗反转录病毒治疗(highly active antiretroviral therapy,HAART)系列的CD4+T,CD8+T及B细胞进行检测,明确不同细胞亚群及HAART治疗的不同阶段是否存在整合的HIV-1 DNA。方法收集20例HIV-1感染患者HAART治... 目的应用Alu-LTR PCR方法对高效抗反转录病毒治疗(highly active antiretroviral therapy,HAART)系列的CD4+T,CD8+T及B细胞进行检测,明确不同细胞亚群及HAART治疗的不同阶段是否存在整合的HIV-1 DNA。方法收集20例HIV-1感染患者HAART治疗过程中0、4、12周及10例健康对照的抗凝血标本,纯化CD4+T,CD8+T及B细胞并提取DNA,应用Alu-LTR PCR方法进行检测。结果 20例HIV-1感染者HAART治疗系列中CD4+T细胞及CD8+T细胞成功扩出目的片段,CD8+T细胞所扩条带亮度均低于CD4+T细胞,HAART治疗系列0、4、12周标本所扩条带亮度没有明显差异。B细胞及10例健康者均为阴性。结论 CD4+T及CD8+T细胞存在整合型HIV-1 DNA,HIV储藏库主要存在于CD4+T细胞内。B细胞内不存在整合型HIV-1 DNA。随着HAART治疗的进程,整合型HIV-1 DNA仍然存在,进一步证明HAART不能根除HIV储藏库。 展开更多
关键词 Alu-LTR PCR 整合型人类免疫缺陷病毒-1 CD4+T细胞 CD8+T细胞 B细胞
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荧光原位杂交检测人类免疫缺陷病毒-1 DNA对感染者外周血淋巴细胞染色体的整合
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作者 王典 李练兵 +4 位作者 侯志伟 谢庆东 马明福 康祥锦 黄天华 《汕头大学医学院学报》 2010年第4期196-197,201,F0002,共4页
目的:探讨荧光原位杂交(FISH)检测人类免疫缺陷病毒(HIV-1)前病毒DNA对外周血淋巴细胞(PBL)染色体整合的可行性与效率。方法:收集3例HIV-1感染者,常规制备其PBL染色体,采用FISH方法,以生物素标记的HIV-1gag及HIV-1pol的cDNA作为探针,检... 目的:探讨荧光原位杂交(FISH)检测人类免疫缺陷病毒(HIV-1)前病毒DNA对外周血淋巴细胞(PBL)染色体整合的可行性与效率。方法:收集3例HIV-1感染者,常规制备其PBL染色体,采用FISH方法,以生物素标记的HIV-1gag及HIV-1pol的cDNA作为探针,检测HIV前病毒在其中的整合。结果:观察了172套来源于3位感染者PBL的染色体,6套有阳性荧光信号。结论:FISH可用于检测HIV前病毒DNA对患者PBL染色体整合,且是一种灵敏、可靠的方法。 展开更多
关键词 荧光原位杂交 人类免疫缺陷病毒 整合 外周血淋巴细胞染色体
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Bilateral Peripheral Facial Paralysis Combined with HIV Meningitis During Acute HIV-1 Infection: A Case Report 被引量:1
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作者 吴焱 宋歌 +1 位作者 魏春波 伦文辉 《Chinese Medical Sciences Journal》 CAS CSCD 2019年第1期55-59,共5页
Here we reported a Chinese case of bilateral peripheral facial paralysis(PFP) in human immunodeficiency virusc(HIV) infected population. A 38-year-old homosexual male patient was referred to our hospital for bilateral... Here we reported a Chinese case of bilateral peripheral facial paralysis(PFP) in human immunodeficiency virusc(HIV) infected population. A 38-year-old homosexual male patient was referred to our hospital for bilateral facial paralysis. 21 days prior to admission he had developed high fever, chills, headache, fatigue, general malaise, nausea and vomiting. Neurological examination revealed bilateral ptosis of lower lip and cheeks, as well as failure of bilateral eyes closure. Analysis of cerebrospinal fluid(CSF) revealed pleocytosis, a marked rise of micro total protein and a marked rise of intrathecal lgG synthesis. The result of HIV-1 serology was positive by ELISA and that was confirmed by western blot. His CD4^+ cell count was 180 cells/mm^3. HIV-1 viral load in CSF was almost 10 times higher than that in plasma. The patient's condition improved steadily and experienced complete resolution of bilateral PFP after 2 months. 展开更多
关键词 human immunodeficiency virus ACQUIRED immune deficiency syndrome ACUTE human immunodeficiency virus-1 infection peripheral facial PARALYSIS
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Microbial translocation, residual viremia and immune senescence in the pathogenesis of HIV-1 infection
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作者 Alessandra Fantauzzi Francesca Falasca +4 位作者 Gabriella d’Ettorre Eugenio Nelson Cavallari Ombretta Turriziani Vincenzo Vullo Ivano Mezzaroma 《World Journal of Clinical Infectious Diseases》 2013年第4期47-57,共11页
The pathophysiological mechanisms that underlie the progression of human immunodeficiency virus-1(HIV-1) disease to full-blown AIDS are not well understood. Findings suggest that, during HIV-1 infection, plasma lipopo... The pathophysiological mechanisms that underlie the progression of human immunodeficiency virus-1(HIV-1) disease to full-blown AIDS are not well understood. Findings suggest that, during HIV-1 infection, plasma lipopolysaccharide(LPS) levels, which are used as an indicator of microbial translocation(MT), are elevated throughout the acute and chronic phases of HIV-1 disease. The translocation of bacterial products through the damaged gastrointestinal barrier into the systemic circulation has been described as a driver of immune activation. In contrast, comorbidities that are associated with HIV-1 infection have been attributed to chronic inflammation and immune system dysfunction secondary to MT or low-level HIV-1 replication in plasma and cell reservoirs. Moreover, accelerated aging is significantly associated with chronic inflammation, immune activation, and immune senescence. In this review, we aimed to investigate the role of inflammation as a pivotal marker in the pathogenesis of HIV-1 disease. We will discuss the key features of chronic inflammation and immune activation that are observed during the natural course of the disease and those features that are detected in c ART-modified infection. The review will focus on the following aspects of HIV-1 infection:(1) MT;(2) the role of residual viremia; and(3) "immune senescence" or "inflammaging." Many questions remain unanswered about the potential mechanisms that are involved in HIV-1 pathogenesis. Further studies are needed to better investigate the mechanisms that underlie immune activation and their correlation with HIV-1 disease progression. 展开更多
关键词 human immunodeficiency virus-1 Combined ANTIRETROVIRAL therapy IMMUNE activation Microbial TRANSLOCATION RESIDUAL VIREMIA IMMUNE senescence
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HIV-1整合位点分布机制及检测的研究进展
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作者 孙孜璇 韩婧婉 +4 位作者 李敬云 李韩平 王晓林 温红玲 李林 《中华医院感染学杂志》 CAS CSCD 北大核心 2024年第11期1755-1760,共6页
艾滋病是由人类免疫缺陷病毒1型(HIV-1)引起的慢性传染性疾病,对人类的生命健康构成了严重威胁.整合是HIV-1病毒复制生命周期的关键环节,不同于新冠病毒等非整合型病毒,HIV-1自身基因编码的逆转录酶和整合酶,可帮助病毒整合入宿主细胞... 艾滋病是由人类免疫缺陷病毒1型(HIV-1)引起的慢性传染性疾病,对人类的生命健康构成了严重威胁.整合是HIV-1病毒复制生命周期的关键环节,不同于新冠病毒等非整合型病毒,HIV-1自身基因编码的逆转录酶和整合酶,可帮助病毒整合入宿主细胞基因组,同步复制,确保病毒的遗传信息长期存在于宿主细胞中.然而HIV-1整合位点的选择不是随机的,而是与染色体结构和宿主基因功能等紧密相关.本文综述了有关HIV-1整合位点的检测方法、分布特征及影响其选择的因素等方面的研究进展,旨在为艾滋病的精准防控、治疗,乃至最终治愈提供信息参考. 展开更多
关键词 人类免疫缺陷病毒1 整合位点 分布特征 影响因素
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Changing roles of CD3^(+)CD8^(low) T cells in combating HIV-1 infection 被引量:2
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作者 Xin Zhang Xiuwen Wang +11 位作者 Ling Qin Xiaofan Lu Zhiying Liu Zhen Li Lin Yuan Rui Wang Junyan Jin Zhenglai Ma Hao Wu Yonghong Zhang Tong Zhang Bin Su 《Chinese Medical Journal》 SCIE CAS CSCD 2023年第4期433-445,共13页
Background:Cluster of differentiation 8(CD8 T)cells play critical roles in eradicating human immunodeficiency virus(HIV)-1 infection,but little is known about the effects of T cells expressing CD8 at low levels(CD8^(l... Background:Cluster of differentiation 8(CD8 T)cells play critical roles in eradicating human immunodeficiency virus(HIV)-1 infection,but little is known about the effects of T cells expressing CD8 at low levels(CD8^(low))or high levels(CD8^(high))on HIV-1 replication inhibition after HIV-1 invasion into individual.Methods:Nineteen patients who had been acutely infected with HIV-1(AHI)and 20 patients with chronic infection(CHI)for≥2 years were enrolled in this study to investigate the dynamics of the quantity,activation,and immune responses of CD3^(+)CD8^(low) T cells and their counterpart CD3^(+)CD8^(high) T cells at different stages of HIV-1 infection.Results:Compared with healthy donors,CD3^(+)CD8^(low) T cells expanded in HIV-1-infected individuals at different stages of infection.As HIV-1 infection progressed,CD3^(+)CD8^(low) T cells gradually decreased.Simultaneously,CD3^(+)CD8^(high) T cells was significantly reduced in the first month of AHI and then increased gradually as HIV-1 infection progressed.The classical activation of CD3^(+)CD8^(low) T cells was highest in the first month of AHI and then reduced as HIV-1 infection progressed and entered the chronic stage.Meanwhile,activated CD38^(-)HLA-DR^(+)CD8^(low) T cells did not increase in the first month of AHI,and the number of these cells was inversely associated with viral load(r=-0.664,P=0.004)but positively associated with the CD4 T-cell count(r=0.586,P=0.014).Increased programmed cell death protein 1(PD-1)abundance on CD3^(+)CD8^(low) T cells was observed from the 1st month of AHI but did not continue to be enhanced,while a significant T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif(ITIM)domains(TIGIT)abundance increase was observed in the 12th month of infection.Furthermore,increased PD-1 and TIGIT abundance on CD3^(+)CD8^(low) T cells was associated with a low CD4 T-cell count(PD-1:r=-0.456,P=0.043;TIGIT:r=-0.488,P=0.029)in CHI.Nonetheless,the nonincrease in PD-1 expression on classically activated CD3^(+)CD8^(low) T cells was inversely associated with HIV-1 viremia in the first month of AHI(r=-0.578,P=0.015).Notably,in the first month of AHI,few CD3^(+)CD8^(low) T cells,but comparable amounts of CD3^(+)CD8^(high) T cells,responded to Gag peptides.Then,weaker HIV-1-specific T-cell responses were induced in CD3^(+)CD8^(low) T cells than CD3^(+)CD8^(high) T cells at the 3rd and 12th months of AHI and in CHI.Conclusions:Our findings suggest that CD3^(+)CD8^(low) T cells play an anti-HIV role in the first month of infection due to their abundance but induce a weak HIV-1-specific immune response.Subsequently,CD3^(+)CD8^(low) T-cell number decreased gradually as infection persisted,and their anti-HIV functions were inferior to those of CD3^(+)CD8^(high) T cells. 展开更多
关键词 Acute human immunodeficiency virus-1 infection HIV CD3^(+)CD8^(low)T cells Immune activation Programmed cell death protein 1 T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains
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Identification of interaction between HIV-1 glycoprotein 41 and integrase
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作者 Xiaowei Zhang Fei Zhang +6 位作者 Xiaohe Ma Xing Zhao Wei Li Zhiping Zhang Jibin Zhang Xian-En Zhang Zongqiang Cui 《Virologica Sinica》 SCIE CAS CSCD 2016年第5期415-424,共10页
Human immunodeficiency virus-1 (HIV-1)encodes 15 viral proteins. Protein-protein interactions play a large role in the function of these proteins. In this study, we attempted to identify novel interactions between t... Human immunodeficiency virus-1 (HIV-1)encodes 15 viral proteins. Protein-protein interactions play a large role in the function of these proteins. In this study, we attempted to identify novel interactions between the HIV-1 proteins to better understand the role played by viral protein-protein interactions in the life cycle of HIV-I. Genes encoding the 15 viral proteins from the HIV-1 strain AD8 were inserted into the plasmids of a yeast two-hybrid system. By screening 120 pairs of proteins, interactions between seven pairs were found. This led to the discovery of an interaction between the HIV-1 proteins integrase (IN) and glycoprotein 41 (gp41), which was confirmed by both co-immunoprecipitation (Co-IP) assays and fluorescence resonance energy transfer (FRET) imaging in live cells. In addition, it was found that the amino acids at positions 76-100 of gp41 are required for it to bind to IN. Deletion of this region from gp41 prevented its interaction with IN and reduced the production of HIV-1 in 293T cells. This study provides new information on HIV-1 protein-protein interactions which improves the understanding of the biological functions of gp41 and IN during the virus life cycle. 展开更多
关键词 human immunodeficiency virus-1 (HIV-1 glycoprotein 41 (gp41 integrase (IN) protein-protein interactions yeast two-hybrid assay
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Functional study of p38 mitogen-activated protein kinase based on cell-penetrating peptide delivery system
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作者 Liping Yang Yongming Yao Zhiyong Sheng Xiaomei Zhu Yong Jiang 《Journal of Geriatric Cardiology》 SCIE CAS CSCD 2009年第2期108-114,共7页
Objective p38 Mitogen-activated protein kinase (MAPK) is a crossing center of various pathways. In this study, protein transduction system based on human immunodeficiency virus (HIV)-1 transactivator of transcript... Objective p38 Mitogen-activated protein kinase (MAPK) is a crossing center of various pathways. In this study, protein transduction system based on human immunodeficiency virus (HIV)-1 transactivator of transcription (TAT), which is an efficient delivery peptide of the foreign proteins into cells, was employed to study p38 MAPK functions in eukaryotic cells. Methods p38 And its dominant negative form, p38AF, were constructed into pET-His-TAT vector correctly to verify that the recombinant plasmids were well-founded through restriction enzyme digestion and DNA sequencing. The two proteins, His-TAT-p38 and His-TAT-p38AF, were expressed and purified in Escherichia coli by SDS-PAGE. Then they were incubated with ECV304 cells respectively and readily transduced into cells in a time-dependent and dose-dependent manner. The cells were stimulated by sorbitol. Activating transcription factor (ATF) 2 phosphorylation level was checked using Western blot to assess the activity of endogenous p38. Results Compared with controls, it was found that His-TAT-p38 increased the level ofATF2 phosphorylation in sorbitol-stimulated ECV304 cells, while His-TAT-p38AF inhibited it, indicating p38 MAPK protein delivery system based on TAT was constructed successfully. TAT-p38 and its dominant negative form possessed high biological activity after transduction into ECV304 cells by TAT protein delivery system. The results showed that p38AF fused with TAT could inhibit the transduction of endogenous p38 signal pathway in part, and other pathway might regulate p38 phosphorylation. Conclusions Our study provides a novel pathway to inhibit p38 signal pathway and establish a new method to study p38 function. 展开更多
关键词 human immunodeficiency virus-1 transactivator of transcription p38 mitogen-activated protein kinase protein transduction: sorbitol
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UM15 reinforces a lymphocyte-mimicking nanotrap for precise HIV-1 inhibition
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作者 Jinbang Zhang Zhengyang Li +13 位作者 Jiaxin Li Hui Li Junwei Che Te Zhao Pengfei Zou Jingwan Han Yang Yang Meiyan Yang Yuli Wang Wei Gong Haihua Xiao Zhiping Li Lin Li Chunsheng Gao 《Nano Research》 SCIE EI CSCD 2023年第7期9906-9920,共15页
Even the potential of T cell-mimicking nanotrap for long term viral control due to its overcoming of human immunodeficiency virus(HIV)genetic diversity and viral resistance,the robust HIV inhibition was not expected b... Even the potential of T cell-mimicking nanotrap for long term viral control due to its overcoming of human immunodeficiency virus(HIV)genetic diversity and viral resistance,the robust HIV inhibition was not expected because these nanotraps displayed no obvious advantages compared with the infinite host cells.Herein,a glycoprotein 120(gp120)-targeting polypeptide UM15 reinforced lymphocyte-mimicking nanotrap was constructed,and its improved HIV-1 inhibiting efficacy was validated.According to the results,the constructed nanotraps exhibited evident escaping ability from uptake of the mononuclear phagocyte system and highly improved binding ability with gp120 proteins.The constructed nanotraps neutralized all tested HIV-1 pseudo typed viruses with IC80 of 21.0μg/mL,and inhibited both X4-tropic and R5-tropic HIV-1 with IC80 of 34.4 and 20.6μg/mL,respectively.Approximately 40%of gp120 was observed to be shed from pseudo virus,and above 40%bystander T cells were prevented from gp120-induced death by the constructed nanotraps.The safety of the constructed nanotraps was confirmed both in vitro and in mice.Therefore,the constructed nanotraps could specifically neutralize free HIV-1,selectively bind with gp120 expressing HIV-1 infected cells,cause gp120 shedding,inhibit gp120-induced bystander T cell killing on the premise of safety,and were considered as promising therapeutic agents for precise inhibition of HIV. 展开更多
关键词 nanotrap lymphocyte membrane UM15 human immunodeficiency virus-1(HIV-1) glycoprotein 120(gp120)
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Heterogeneity of HIV-1 latent reservoirs 被引量:1
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作者 Jia-Cong Zhao Kai Deng 《Chinese Medical Journal》 SCIE CAS CSCD 2020年第23期2867-2873,共7页
Antiretroviral therapy(ART)can effectively inhibit human immunodeficiency virus-1(HIV-1)replication,but is not curative due to the existence of a stable viral latent reservoir harboring replication-competent proviruse... Antiretroviral therapy(ART)can effectively inhibit human immunodeficiency virus-1(HIV-1)replication,but is not curative due to the existence of a stable viral latent reservoir harboring replication-competent proviruses.In order to reduce or eliminate the HIV-1 latent reservoir,characteristics of the latently infected cells need to be intensively studied,and a comprehensive understanding of the heterogenous nature of the latent reservoir will be critical to develop novel therapeutic strategies.Here,we discuss the different cell types and mechanisms contributing to the complexity and heterogeneity of HIV-1 latent reservoirs,and summarize the key challenges to the development of cure strategies for acquired immunodeficiency syndrome(AIDS). 展开更多
关键词 Clonal expansion HETEROGENEITY human immunodeficiency virus-1 HIV-1 integration sites Latent reservoirs
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Multiple Roles of HIV-1 Capsid during the Virus Replication Cycle 被引量:1
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作者 Mariia Novikova Yulan Zhang +1 位作者 Eric O. Freed Ke Peng 《Virologica Sinica》 SCIE CAS CSCD 2019年第2期119-134,共16页
Human immunodeficiency virus-1 capsid(HIV-1 CA) is involved in different stages of the viral replication cycle. During virion assembly, CA drives the formation of the hexameric lattice in immature viral particles, whi... Human immunodeficiency virus-1 capsid(HIV-1 CA) is involved in different stages of the viral replication cycle. During virion assembly, CA drives the formation of the hexameric lattice in immature viral particles, while in mature virions CA monomers assemble in cone-shaped cores surrounding the viral RNA genome and associated proteins. In addition to its functions in late stages of the viral replication cycle, CA plays key roles in a number of processes during early phases of HIV-1 infection including trafficking, uncoating, recognition by host cellular proteins and nuclear import of the viral preintegration complex. As a result of efficient cooperation of CA with other viral and cellular proteins, integration of the viral genetic material into the host genome, which is an essential step for productive viral infection, successfully occurs. In this review, we will summarize available data on CA functions in HIV-1 replication, describing in detail its roles in late and early phases of the viral replication cycle. 展开更多
关键词 human immunodeficiency virus-1 (HIV-1) CAPSID (CA) Assembly Post ENTRY UNCOATING and nuclear IMPORT Inhibitor
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Deubiquitinase ubiquitin-specific protease 3 (USP3) inhibits HIV-1 replication via promoting APOBEC3G (A3G) expression in both enzyme activity-dependent and -independent manners
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作者 Simin Zhao Baisong Zheng +5 位作者 Liuli Wang Wenzhe Cui Chunlai Jiang Zhuo Li Wenying Gao Wenyan Zhang 《Chinese Medical Journal》 SCIE CAS CSCD 2022年第22期2706-2717,共12页
Background: Ubiquitination plays an essential role in many biological processes, including viral infection, and can be reversed by deubiquitinating enzymes (DUBs). Although some studies discovered that DUBs inhibit or... Background: Ubiquitination plays an essential role in many biological processes, including viral infection, and can be reversed by deubiquitinating enzymes (DUBs). Although some studies discovered that DUBs inhibit or enhance viral infection by various mechanisms, there is lack of information on the role of DUBs in virus regulation, which needs to be further investigated.Methods: Immunoblotting, real-time polymerase chain reaction,in vivo/in vitro deubiquitination, protein immunoprecipitation, immunofluorescence, and co-localization biological techniques were employed to examine the effect of ubiquitin-specific protease 3 (USP3) on APOBEC3G (A3G) stability and human immunodeficiency virus (HIV) replication. To analyse the relationship between USP3 and HIV disease progression, we recruited 20 HIV-infected patients to detect the levels of USP3 and A3G in peripheral blood and analysed their correlation with CD4^(+) T-cell counts. Correlation was estimated by Pearson correlation coefficients (for parametric data).Results: The results demonstrated that USP3 specifically inhibits HIV-1 replication in an A3G-dependent manner. Further investigation found that USP3 stabilized 90% to 95% of A3G expression by deubiquitinating Vif-mediated polyubiquitination and blocking its degradation in an enzyme-dependent manner. It also enhances the A3G messenger RNA (mRNA) level by binding to A3G mRNA and stabilizing it in an enzyme-independent manner. Moreover, USP3 expression was positively correlated with A3G expression (r= 0.5110) and CD4^(+) T-cell counts (r= 0.5083) in HIV-1-infected patients.Conclusions: USP3 restricts HIV-1 viral infections by increasing the expression of the antiviral factor A3G. Therefore, USP3 may be an important target for drug development and serve as a novel therapeutic strategy against viral infections. 展开更多
关键词 APOBEC3G Ubiquitin-specific protease 3 DEUBIQUITINATION human immunodeficiency virus-1 Vif human immunodeficiency virus Deubiquitinase
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人免疫缺陷病毒对不同黏膜上皮细胞系的感染能力的研究
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作者 李悦 赵辉 +5 位作者 杜军 全宇 邢辉 陈启民 邵一鸣 杨贵波 《中华微生物学和免疫学杂志》 CAS CSCD 北大核心 2008年第7期577-581,共5页
目的研究人免疫缺陷病毒(HIV-1)对不同黏膜上皮细胞系的感染能力。方法用实验室株HIV-1 SF33和2株原代HIV-1(02010561,02010141)分别感染Caco-2、T-84和HeLa3株黏膜上皮细胞和MT-4细胞。接种病毒后间隔3~4d采集培养上清检测P24并... 目的研究人免疫缺陷病毒(HIV-1)对不同黏膜上皮细胞系的感染能力。方法用实验室株HIV-1 SF33和2株原代HIV-1(02010561,02010141)分别感染Caco-2、T-84和HeLa3株黏膜上皮细胞和MT-4细胞。接种病毒后间隔3~4d采集培养上清检测P24并用实时定量RT-PCR检测病毒载量;采集细胞提取DNA并用PCR法检测感染细胞中病毒DNA和整合入细胞基因组内的病毒DNA。结果所用3株病毒都可以产毒性地感染阳性对照细胞MT-4,对整合病毒DNA的PCR检测发现它们均能够整合到MT-4细胞基因组内;实验室适应株HIV-1 SF33虽然能够感染所有3株上皮细胞,但它不能整合入Caco-2细胞的基因组中;虽然2株原代分离病毒均能感染T-84细胞,但只有HIV-1 02020141能够整合入T-84细胞的基因组中,原代分离病毒HIV-1 02010561能够感染HeLa细胞,但不能整合到其基因组中。结论虽然HIV-1的实验室毒株和原代分离毒株都可能感染黏膜上皮细胞,但它们在黏膜上皮细胞中建立稳定产毒性感染(感染并产生病毒)的能力因细胞和毒株不同而异。 展开更多
关键词 人免疫缺陷病毒 黏膜上皮细胞 感染 整合
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Low rate of pre-exposure prophylaxis and post-exposure prophylaxis uptake and high prevalence of transmitted drug resistance among newly diagnosed primary HIV infections in Shenzhen, China: a real-world retrospective study 被引量:1
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作者 Qiaoli Peng Xiaoning Liu +16 位作者 Xian Tang Qiuyue Zhang Jin Zhao Chenli Zheng Fang Zhao Yang Zhou Lukun Zhang Liqin Sun Haitao Zhang Xinyun Jia Ying Song Tingzhi Cao Siyuan Wang Man Rao Zhiwei Chen Hui Wang Yun He 《Chinese Medical Journal》 SCIE CAS CSCD 2022年第22期2730-2737,共8页
Background: Understanding the characteristics of newly diagnosed primary human deficiency virus-1 (HIV-1) infection in the context of the post-antiretroviral therapy era and HIV drug prophylaxis is essential for achie... Background: Understanding the characteristics of newly diagnosed primary human deficiency virus-1 (HIV-1) infection in the context of the post-antiretroviral therapy era and HIV drug prophylaxis is essential for achieving the new target of 95-95-95-95 by 2025. This study reported the characteristics of newly diagnosed primary HIV-1 infection in Shenzhen.Methods: This is a real-world retrospective study. Eighty-seven newly diagnosed primary HIV-1-infected patients were recruited from January 2021 to March 2022 at the Third People’s Hospital of Shenzhen. Demographic, epidemiological, diagnostic, drug resistance, and medical data were described and analyzed.Results: Overall, 96.6% (84/87) of the newly identified primary HIV-1-infected patients were male, including 88.5% (77/87) men have sex with men (MSM), with a median age of 29.0 years (Q_(1)-Q_(3): 24.0-34.0 years);of these, 85.1% (74/87) reported high-risk sexual behaviors with casual partners. The rate of condom usage was only 28.7% (25/87). The overall rate of pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) was 8.0% (7/87, including 4 PrEP and 3 PEP cases) around the potential exposure, although 41.4% of the patients had prior awareness of such interventions. Moreover, only 19.5% (17/87) had previously used PrEP or PEP. Of those, 58.8% (10/17) of the patients obtained drugs from the internet, and only 35.3% (6/17) reported good compliance. A total of 54.0% (47/87) of subjects were diagnosed by the HIV nucleic acid test. Acute retroviral syndrome appeared in 54.0% (47/87) of patients. The prevalence of transmitted drug resistance (TDR) mutation was 33.9% (19/56), including 6 (10.7%) against nucleoside reverse transcriptase inhibitor (NRTI) plus non-nucleoside reverse transcriptase inhibitor (NNRTI), 8 (14.3%) against NNRTI, and 5 (8.9%) against protease inhibitor (PI) only.Conclusions: Owing to the low utilization rate and incorrect usage of PrEP and PEP, massive efforts are needed to promote HIV-preventive strategies in the MSM population. The extremely high prevalence of TDR mutation in this population implies the need for future pretreatment drug resistance surveillance. 展开更多
关键词 Antiretroviral therapy Drug resistance human immunodeficiency virus-1 Post-exposure prophylaxis Pre-exposure prophylaxis
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