人免疫缺陷病毒1型潜伏感染激活剂研究现状

高效抗逆转录病毒治疗(HAART)对控制HIV-1进展效果显著,但病毒潜伏库的存在导致病毒无法完全清除.HIV-1感染后,潜伏库建立早,半衰期长,长期处于静息状态,是根治HIV-1感染的主要障碍之一.目前清除病毒潜伏库的方法有潜伏感染激活剂、免疫治疗和基因治疗等.此文主要讨论了HIV-1潜伏感染激活剂相关内容.     

体外研究HIV-1潜伏库实验方法进展

HIV-1在未治疗的艾滋病患者体内,虽可以持续复制,但也可潜伏在细胞内以逃避宿主的免疫清除,这一现象即病毒潜伏.由于病毒潜伏对抗病毒治疗带来了挑战,也引起人们的高度关注.此文对体外研究HIV-1潜伏库的实验方法 进展进行综述.     

体外研究HIV-1潜伏库实验方法进展

HIV-1在未治疗的艾滋病患者体内,虽可以持续复制,但也可潜伏在细胞内以逃避宿主的免疫清除,这一现象即病毒潜伏.由于病毒潜伏对抗病毒治疗带来了挑战,也引起人们的高度关注.此文对体外研究HIV-1潜伏库的实验方法 进展进行综述.     

体外研究HIV-1潜伏库实验方法进展

HIV-1在未治疗的艾滋病患者体内,虽可以持续复制,但也可潜伏在细胞内以逃避宿主的免疫清除,这一现象即病毒潜伏.由于病毒潜伏对抗病毒治疗带来了挑战,也引起人们的高度关注.此文对体外研究HIV-1潜伏库的实验方法 进展进行综述.     

体外研究HIV-1潜伏库实验方法进展

HIV-1在未治疗的艾滋病患者体内,虽可以持续复制,但也可潜伏在细胞内以逃避宿主的免疫清除,这一现象即病毒潜伏.由于病毒潜伏对抗病毒治疗带来了挑战,也引起人们的高度关注.此文对体外研究HIV-1潜伏库的实验方法 进展进行综述.     

体外研究HIV-1潜伏库实验方法进展

HIV-1在未治疗的艾滋病患者体内,虽可以持续复制,但也可潜伏在细胞内以逃避宿主的免疫清除,这一现象即病毒潜伏.由于病毒潜伏对抗病毒治疗带来了挑战,也引起人们的高度关注.此文对体外研究HIV-1潜伏库的实验方法 进展进行综述.     

体外研究HIV-1潜伏库实验方法进展

HIV-1在未治疗的艾滋病患者体内,虽可以持续复制,但也可潜伏在细胞内以逃避宿主的免疫清除,这一现象即病毒潜伏.由于病毒潜伏对抗病毒治疗带来了挑战,也引起人们的高度关注.此文对体外研究HIV-1潜伏库的实验方法 进展进行综述.     

HIV-1病毒储存库的特征及检测方法

HIV-1在未治疗的艾滋病患者体内,虽可以持续复制,但也可潜伏在细胞内以逃避宿主的免疫清除,这一现象即病毒潜伏.由于病毒潜伏对抗病毒治疗带来了挑战,也引起人们的高度关注.此文对体外研究HIV-1潜伏库的实验方法 进展进行综述.     

体外研究HIV-1潜伏库实验方法进展

HIV-1在未治疗的艾滋病患者体内,虽可以持续复制,但也可潜伏在细胞内以逃避宿主的免疫清除,这一现象即病毒潜伏.由于病毒潜伏对抗病毒治疗带来了挑战,也引起人们的高度关注.此文对体外研究HIV-1潜伏库的实验方法 进展进行综述.     

体外研究HIV-1潜伏库实验方法进展

HIV-1在未治疗的艾滋病患者体内,虽可以持续复制,但也可潜伏在细胞内以逃避宿主的免疫清除,这一现象即病毒潜伏.由于病毒潜伏对抗病毒治疗带来了挑战,也引起人们的高度关注.此文对体外研究HIV-1潜伏库的实验方法 进展进行综述.     

艾滋病功能性治愈研究新进展

抗反转录病毒治疗（antiretroviral therapy, ART）虽然能有效抑制HIV 1型（HIV-1），但不能根治AIDS。AIDS功能性治愈须为停止ART后患者体内HIV-1 RNA长期低于检测下限， CD4+ T淋巴细胞数量和机体免疫功能保持正常，这一直是全球研究热点和难点。近年来，AIDS功能性治愈研究在HIV-1储存库激活和清除、免疫治疗、干细胞移植、基因编辑等方面取得了长足进步，本文就此进行综述，为进一步研究提供理论指导。     

Vaccination with a modified vaccinia virus Ankara (MVA)-vectored HIV-1 immunogen induces modest vector-specific T cell responses in human subjects

We investigated whether vaccination of healthy HIV-seronegative and HIV-1-seropositive antiretroviral therapy-treated subjects with recombinant modified vaccinia virus Ankara expressing an HIV-1 immunogen (MVA.HIVA) induced MVA-specific T cell responses. Using IFN-γ Elispot assays, we observed new or increased responses to MVA virus in 52% of HIV-seronegative subjects and 93% HIV-1 seropositive subjects; MVA-specific T cell frequencies were generally low and correlated poorly with T cell responses to the HIV-1 immunogen. In two vaccinees, responses were mapped to CD8+ T cell epitopes present in replication-competent vaccinia virus. These data support further evaluation of MVA as a viral vector for HIV-1 immunogens.     

云南省2000-2007年静脉吸毒者、性病就诊者和孕产妇HIV-1新近感染率及流行趋势变化

目的 在云南省艾滋病监测哨点用BED-CEIA方法 开展HIV-1新近感染检测,估箅新近感染率和流行趋势.方法 收集2000-2007年云南省静脉吸毒(IDU)监测哨点、性病门诊监测哨点和孕产妇监测哨点样本,采用连续的横断面调查,对经过血清学检测确认为HIV-1阳性样本再进行BED-CEIA检测.结果 研究样本共计144 780份,检出HIV-1阳性样本4932份,完成BED-CEIA检测4678份,判为新近感染样本723份.相邻两年样本合并分析,2000-2007年IDU监测哨点HIV-1平均感染率在18.2%～26.9%之间,新近感染率分别为14.65%、6.21%、4.06%、2.23%;性病门诊监测哨点HIV-1平均感染率在1.6%～3.2%之间,新近感染率分别为1.46%、0.76%、0.52%、0.33%;孕产妇监测哨点HIV-1平均感染率在0.2%～0.5%之间,新近感染率分别为0.16%、0.11%、0.10%、0.09%.结论 三类监测人群中,IDU、性病门诊就诊者和孕产妇新近感染率有所下降.     

HLA-Ⅰ基因型对HIV-1感染患儿特异性细胞毒性T细胞应答的影响

目的 对HIV-1感染患儿的人类白细胞抗原(HLA)-Ⅰ基因型进行分析,探讨其对HIV-1特异性CTL应答的影响.方法 采用酶联免疫斑点技术(ELISPOT),以HIV-1 P24区域的氨基酸序列人工合成的12个重叠肽段组成的肽段库作为特异性抗原表位,对5例接受HAART后的HIV-1感染患儿外周血单核细胞(PBMC)的IFN-γ分泌细胞频数进行测定研究.同时,还采用了PCR-序列特异引物技术(PCR-SSP)及PCR-直接碱基序列分析基因分型技术(PCR-SBT)对这5例患儿进行了HLA-Ⅰ等位基因分型及HLA-B*高分辨等位基因分型.结果 5例HIV-1感染息儿中,4例HLA-B*基因型为B*40,其中3例为HLA-B*4001,1例为HLA-B*4002.其HIV-1抗原特异性CTL应答水平差异明显.5例患儿均未出现免疫重建炎症综合征.结论 基因型为HLA-B*40的儿童可能更易感染HIV-1,HLA-B*40可能影响HIV-1感染患儿的抗原特异性CTL应答.     

HIV-1重组病毒载体疫苗研究进展

研制有效的疫苗是预防和控制HIV-1的理想途径.重组活病毒载体疫苗能诱导广泛的细胞和体液免疫应答,并在临床试验中展现出良好的应用前景,已成为当前HIV-1疫苗研究的一个热点.此文就近年来针对HIV-1的各种重组病毒载体疫苗研究进展作了综述.     

Phenotypic and functional characteristics of HIV-specific CD8 T cells and gag sequence variability after autologous dendritic cells based therapeutic vaccine

A decrease in HIV-1 specific CD8 T-cell responses associated with a partial control of viral replication occurred in 12 HIV-1-infected patients during autologous dendritic cells vaccination. HIV CD8 T cells were detected in 6/10 patients during immunizations, increasing after HAART discontinuation in 3 of them. Tet+ CD8 cells mainly had an effector phenotype (CD45RA−/+ CCR7− and CD28− and Perf+/−) and maintained IFN-γ release throughout follow-up. By contrast, patients with CD45RA−/+ CCR7+ Perf+ HIV-specific cells showed a decrease in peptide-specific IFN-γ production during vaccinations while levels were recovered when off HAART. No major mutations in either Gag p24 and p17 immunodominant epitopes were observed that might have explained the impaired CD8+ T-cell responses. Taken together, heterogeneity in the maturation status of HIV-specific CD8 T cells may be partially involved in the drop of peptide-specific IFN-γ production during immunizations.     

Interferon gamma (IFN-γ) negative CD4+ and CD8+ T-cells can produce immune mediators in response to viral antigens

Evaluation of antigen-specific T-cell responses to viral antigens is frequently performed on IFN-γ secreting cells. However, T-cells are capable of producing many more functions than just IFN-γ, some of which, like Perforin, are associated with immune protection in HIV-1 disease elite controllers. We evaluated the extent of missed T-cell functions when IFN-γ secretion is used as a surrogate marker for further evaluation of T-cell functions. Intracellular cytokine staining assay and flow cytometry were used to assess peripheral blood mononuclear cells (PBMCs) from 31 HIV-infected ART-naive individuals for the extent to which gated CD4+ and CD8+ IFN-γ producing and non-producing T-cells also secreted IL-2, Perforin, and TNF-α functions. Similarly, the extent of missed virus-specific responses in IFN-γ ELISpot assay negative T-cells from 5 HIV-1 uninfected individuals was evaluated. Cells from HIV-infected individuals were stimulated with pooled consensus group M (Con M) peptides; and those from healthy individuals were stimulated with pooled adenovirus (Ad) peptides. Overall, frequencies of virus-specific IFN-γ secreting CD4+ and CD8+ cells were low. Proportions of IFN-γ negative CD4+ expressing IL-2, Perforin, or TNF-α to Con M were significantly higher (5 of 7 functional profiles) than the corresponding IFN-γ positive CD4+ (0 of 7) T-cell phenotype, p?=?0.02; Fisher’s Exact test. Likewise, proportions of CD8+ T-cells expressing other functions were significantly higher in 4 of the 7 IFN-γ negative CD8+ T-cells. Notably, newly stimulated Perforin, identified as Perforin co-expression with IL-2 or TNF-α, was significantly higher in IFN-γ negative CD8+ T-cell than in the positive CD8+ T-cells. Using SEB, lower responses in IFN-γ positive cells were most associated with CD4+ than CD8+ T-cells. These findings suggest that studies evaluating immunogenicity in response to HIV and Adenovirus viral antigens should not only evaluate T-cell responsiveness among IFN-γ producing cells but also among those T-cells that do not express IFN-γ.     

HIV-1感染者抗病毒治疗后HIV-1 DNA载量动力学变化及影响因素分析

目的:分析云南省德宏傣族景颇族自治州（德宏州）HIV感染者抗病毒治疗后HIV-1 DNA载量的动力学变化及影响因素,为HIV-1 DNA定量检测的临床应用提供参考依据。方法:研究对象来源于德宏州CDC建立的2009-2018年HIV新发感染队列,构建HIV-1 DNA载量随抗病毒治疗时间动力学变化曲线图。采用logis...     

Evaluation of yellow fever virus 17D strain as a new vector for HIV-1 vaccine development

The failure to develop an effective vaccine against HIV-1 infection has led the research community to seek new ways of raising qualitatively different antibody and cellular immune responses. Towards this goal, we investigated the yellow fever 17D vaccine strain (YF17D), one of the most effective vaccines ever made, as a platform for HIV-1 vaccine development. A test antigen, HIV-1 p24 (clade B consensus), was inserted near the 5′ end of YF17D, in frame and upstream of the polyprotein (YF-5′/p24), or between the envelope and the first non-structural protein (YF-E/p24/NS1). In vitro characterization of these recombinants indicated that the gene insert was more stable in the context of YF-E/p24/NS1. This was confirmed in immunogenicity studies in mice. CD8⁺ IFN-γ T-cell responses against p24 were elicited by the YF17D recombinants, as were specific CD4⁺ T cells expressing IFN-γ and IL-2. A balanced CD4⁺ and CD8⁺ T-cell response was notable, as was the polyfunctionality of the responding cells. Finally, the protective efficacy of the YF17D recombinants, particularly YF-E/p24/NS1, in mice challenged with a vaccinia expressing HIV-1 Gag was demonstrated. These results suggest that YF17D warrants serious consideration as a live-attenuated vector for HIV-1 vaccine development.     

Long-term survival after infection with human immunodeficiency virus type 1 (HIV-1) among homosexual men in hepatitis B vaccine trial cohorts in Amsterdam, New York City, and San Francisco, 1978-1995

Information on long-term survival after infection with human immunodeficiency virus type 1 (HIV-1) is limited. In hepatitis B vaccine trials in Amsterdam, New York City, and San Francisco, 362 gay men were followed up to 18 years (1978-1995). The median survival time from seroconversion was 12.1 years (95% confidence interval: 11.4, 12.9). The annual risk of dying increased at a constant rate until 8 years after seroconversion and then leveled off, suggesting a group that is relatively resistant to progression. These data provide a picture of the natural history of HIV-1 infection, especially in the era prior to widespread use of highly effective treatments.