HIV

HIV
  • 文章类型: Journal Article
    COVID-19大流行给艾滋病毒护理服务带来了挑战。远程在线服务可能为向艾滋病毒感染者(PLHIV)提供卫生服务提供有效的方法。在中国,很少有研究关注远程医疗服务对PLHIV的疗效以及通过在线服务进行抗逆转录病毒治疗的效果。
    我们开发了一个名为“否”的平台。8健康”,用于2022年1月21日至6月30日在北京提供在线抗逆转录病毒药物收集和交付服务。我们根据病毒载量抑制率评估了在线治疗服务,并比较了通过在线或离线治疗服务接受抗逆转录病毒药物的PLHIV之间社会特征的差异。
    到2022年6月,9528名艾滋病毒感染者接受了门诊治疗服务,其中44.6%(4031/9528)使用在线治疗和送药服务共5590人次。满意率为100%。在2020年和2021年开始抗逆转录病毒治疗(ART)的PLHIV中,病毒载量抑制率分别为96.4%和93.1%。分别。结果显示,病毒载量抑制率为97.9%。关于艾滋病毒快速自我检测,4513名与男性发生性关系的男性使用了在线HIV快速检测服务。用户数量与2021年大致相同,但均略低于2020年。
    这项研究首次评估了中国PLHIV中在线药物收集和递送服务的效果以及病毒学结果。在线服务有助于维持ART服务,但COVID-19大流行仍对病毒载量抑制产生了一些影响。
    UNASSIGNED: The COVID-19 pandemic has created challenges with respect to HIV care services. Remote online services might provide an effective method for health service delivery to people living with HIV (PLHIV). Few studies have focused on the efficacy of telemedical services for PLHIV and the effect of antiretroviral treatment via online services in China.
    UNASSIGNED: We developed a platform called the \"No. 8 Health\" for online antiretroviral drug collection and delivery services in Beijing from January 21 to June 30, 2022. We evaluated the online treatment service according to viral load suppression rates and compared differences in social characteristics between PLHIV who received antiretroviral drugs through online or offline treatment services.
    UNASSIGNED: By June 2022, 9528 PLHIV had received outpatient treatment services, among which 44.6% (4031/9528) used the online treatment and drug delivery services for a total of 5590 person-times. The satisfaction rate was 100%. Rates of viral load suppression among PLHIV who initiated antiretroviral therapy (ART) in 2020 and 2021 were 96.4% and 93.1%, respectively. Results showed that the viral load suppression rate was 97.9%. Regarding HIV rapid self-testing, 4513 men who have sex with men used the online HIV rapid testing service. The number of users was approximately the same as in 2021, but both were slightly lower than those in 2020.
    UNASSIGNED: This study was the first to evaluate the effect of online drug collection and delivery services and virologic outcomes among PLHIV in China. The online service helped with maintenance of ART services, but the COVID-19 pandemic still had some impacts on viral load suppression.
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  • 文章类型: Journal Article
    目标:自2022年5月以来,水痘已在非洲以外广泛传播,对全球人民的健康构成严重威胁,尤其是男男性行为者(MSM)人群。重庆,中国西南的一个省,有相对较大的MSM和艾滋病毒感染者(PLWH)人口,提供有利于水痘广泛传播的条件。在这项研究中,我们调查了重庆地区MSM和PLWH中水痘患者的临床特征,旨在为有针对性的预防的发展提供信息,control,以及水痘的治疗策略。
    方法:我们评估了临床特征,旅行史,发病时间,2022年9月至2023年10月重庆公共卫生医学中心收治的水痘患者皮损分布及数量.同时,收集了一系列临床样本,使用定量聚合酶链反应(qPCR)将目的病原体鉴定为痘病毒.结果以循环阈值(Ct)的形式呈现,这有助于近似病毒载量的量化。
    结果:截至2023年10月11日,重庆市公共卫生医疗中心共报告9例痘病毒感染。确定的所有患者均为男性,属于MSM人群,其中7人(77.8%)感染艾滋病毒,并保持一个保存的免疫系统,同时通过有效的ART实现病毒抑制。我们观察到MSM与有或没有HIV的Mpox之间没有明显的临床差异,没有死亡记录。观察到从皮肤采集的样本中的病毒载量高于从喉咙采集的样本,鼻咽部,血,或者精液.
    结论:在这项回顾性研究中,MSM患者MPXV感染的临床表现一致,无论艾滋病毒状况如何。皮肤和粘膜组织中MPXV病毒载量升高,特别是在生殖器和肛门部位,表明传播更有可能通过直接身体接触而不是呼吸途径或通过暴露于体液。
    OBJECTIVE: Since May 2022, Mpox has spread extensively outside of Africa, posing a serious threat to the health of people globally, and particularly to the men who have sex with men (MSM) population. Chongqing, a province in Southwest China, has relatively large MSM and people living with HIV (PLWH) populations, presenting conditions conducive to the wide dissemination of Mpox. In this study, we investigated the clinical characteristics of Mpox patients among MSM and PLWH in Chongqing, aiming to inform the development of targeted prevention, control, and treatment strategies for Mpox.
    METHODS: We evaluated the clinical characteristics, travel history, time of onset, distribution and number of skin lesions of Mpox patients admitted to the Chongqing Public Health Medical Center between September 2022 and October 2023. Meanwhile, a series of clinical samples were collected and the pathogen of interest was identified as Mpox virus using quantitative polymerase chain reaction (qPCR). The results were presented in the form of cycle thresholds (Ct), which help to approximate the quantification of viral load.
    RESULTS: As of October 11, 2023, the Chongqing Public Health Medical Center reported a total of nine Mpox virus infections. All the patients identified were male and belonged to the MSM population, among whom seven (77.8%) were living with HIV, and maintained a preserved immune system while achieving viral suppression via effective ART. We observed no discernible clinical differences between MSM with Mpox with or without HIV, and no fatalities were recorded. Viral loads were observed to be higher in samples taken from the skin than those from the throat, nasopharynx, blood, or semen.
    CONCLUSIONS: In this retrospective study, the clinical manifestations of MPXV infection appeared consistent among MSM patients, regardless of HIV status. Elevated MPXV viral loads in the skin and mucosal tissues, particularly at genital and anal sites, indicate that transmission is more likely to occur via direct physical contact as opposed to respiratory pathways or through exposure to bodily fluids.
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  • 文章类型: Journal Article
    目标:在中国,超过30%的患者在HIV诊断后30天内未开始治疗.延迟启动对疾病结局有不利影响,并增加艾滋病毒传播。该研究旨在评估以护士为主导的抗逆转录病毒疗法对中国新诊断为HIV的人群的干预效果,以找到最佳的干预实施策略。
    方法:将在湖南四个疾病预防控制中心进行II型混合序贯多重分配随机试验,中国。这项研究将招募447名年龄≥18岁的新诊断为HIV的人,并将他们随机分为两个干预组和一个对照组。除了定期的咨询服务和转介之外,干预组将接受为期4周的培训,基于双系统理论和微推理论的两阶段干预。对照组将遵循目前推荐的转诊程序。主要结果是是否开始治疗,以及它需要的时间长度。研究结果将在基线测量,第15天,第30天,第12周,第24周和第48周。广义估计方程和生存分析将用于比较有效性并探索与抗逆转录病毒治疗开始相关的因素。将收集定性和定量信息,以评估执行结果。
    结论:现有策略主要针对机构层面的因素,很少考虑患者的决策。为了缩小这个差距,我们的目标是开发一种有效的理论驱动的推动策略,以改善早期ART启动。
    结论:这项由护士主导的研究将通过对新诊断为HIV的人采用实施科学策略来帮助防止延迟启动。这项研究有助于联合国到2030年结束艾滋病流行的目标。
    背景:中国临床试验注册ChiCTR2300070140。该试验在招募第一位参与者之前进行了前瞻性登记。
    通过名义小组技术最终确定了推动干预措施,我们邀请了相关领域的五名专家和五名艾滋病毒感染者参加。
    OBJECTIVE: In China, more than 30% of patients have not initiated treatment within 30 days of HIV diagnosis. Delayed initiation has a detrimental influence on disease outcomes and increases HIV transmission. The study aims to evaluate the effectiveness of a nurse-led antiretroviral therapy initiation nudging intervention for people newly diagnosed with HIV in China to find the optimal intervention implementation strategy.
    METHODS: A Hybrid Type II sequential multiple assignment randomized trial will be conducted at four Centers for Disease Control and Prevention in Hunan, China. This study will recruit 447 people newly diagnosed with HIV aged ≥18 years and randomly assign them into two intervention groups and one control group. On top of the regular counselling services and referrals, intervention groups will receive a 4-week, 2-phase intervention based on the dual-system theory and the nudge theory. The control group will follow the currently recommended referral procedures. The primary outcomes are whether treatment is initiated, as well as the length of time it takes. The study outcomes will be measured at the baseline, day 15, day 30, week 12, week 24 and week 48. Generalized estimating equations and survival analysis will be used to compare effectiveness and explore factors associated with antiretroviral therapy initiation. Both qualitative and quantitative information will be collected to assess implementation outcomes.
    CONCLUSIONS: Existing strategies mostly target institutional-level factors, with little consideration given to patients\' decision-making. To close this gap, we aim to develop an effective theory-driven nudging strategy to improve early ART initiation.
    CONCLUSIONS: This nurse-led study will help to prevent delayed initiation by employing implementation science strategies for people newly diagnosed with HIV. This study contributes to the United Nations\' objective of ending the AIDS pandemic by 2030.
    BACKGROUND: Chinese Clinical Trial Registry ChiCTR2300070140. The trial was prospectively registered before the first participant was recruited.
    UNASSIGNED: The nudging intervention was finalized through the Nominal Group Technique where we invited five experts in the related field and five people living with HIV to participate.
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  • 文章类型: Journal Article
    人类免疫缺陷病毒(HIV)仍然是一个至关重要的全球健康问题,迫切需要有效的诊断和监测工具。
    这项研究探索了健康个体唾液代谢组的区别,艾滋病毒感染者,和那些接受高活性抗逆转录病毒治疗(HAART)。利用LC-MS/MS进行详尽的代谢组学分析,我们分析了90例HIV感染者的口腔唾液样本,根据外周血中的CD4计数水平进行分类。
    正交偏最小二乘判别分析(OPLS-DA)和其他分析强调了HIV感染者的显着代谢改变,特别是在能量代谢途径中。值得注意的是,后HAART代谢谱表明大量存在外源代谢物和氨基酸途径的变化,如精氨酸,脯氨酸,和赖氨酸降解。关键代谢产物如柠檬酸,L-谷氨酸,和L-组氨酸被鉴定为疾病进展或恢复的潜在指标。差异代谢物选择和功能富集分析,结合接收机工作特性(ROC)和随机森林分析,确定HIV感染不同阶段的潜在生物标志物。此外,我们的研究检查了口腔代谢物和微生物之间的相互作用,如单纯疱疹病毒1型(HSV1),细菌,和感染艾滋病毒的人身上的真菌,揭示关键的互动。
    本调查旨在帮助了解HIV感染和HAART开始后发生的代谢变化,同时初步提出了通过唾液代谢组学进行诊断和治疗监测的新途径。
    UNASSIGNED: The human immunodeficiency virus (HIV) remains a critical global health issue, with a pressing need for effective diagnostic and monitoring tools.
    UNASSIGNED: This study explored distinctions in salivary metabolome among healthy individuals, individuals with HIV, and those receiving highly active antiretroviral therapy (HAART). Utilizing LC-MS/MS for exhaustive metabolomics profiling, we analyzed 90 oral saliva samples from individuals with HIV, categorized by CD4 count levels in the peripheral blood.
    UNASSIGNED: Orthogonal partial least squares-discriminant analysis (OPLS-DA) and other analyses underscored significant metabolic alterations in individuals with HIV, especially in energy metabolism pathways. Notably, post-HAART metabolic profiles indicated a substantial presence of exogenous metabolites and changes in amino acid pathways like arginine, proline, and lysine degradation. Key metabolites such as citric acid, L-glutamic acid, and L-histidine were identified as potential indicators of disease progression or recovery. Differential metabolite selection and functional enrichment analysis, combined with receiver operating characteristic (ROC) and random forest analyses, pinpointed potential biomarkers for different stages of HIV infection. Additionally, our research examined the interplay between oral metabolites and microorganisms such as herpes simplex virus type 1 (HSV1), bacteria, and fungi in individuals with HIV, revealing crucial interactions.
    UNASSIGNED: This investigation seeks to contribute understanding into the metabolic shifts occurring in HIV infection and following the initiation of HAART, while tentatively proposing novel avenues for diagnostic and treatment monitoring through salivary metabolomics.
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  • 文章类型: Journal Article
    尚无关于应用随机生存森林(RSF)模型预测HIV相关B细胞淋巴瘤的疾病进展的报道。
    纳入2012-2019年南京市第二医院收治的44例HIV相关B细胞淋巴瘤患者。RSF模型被用来寻找生存的预测因子,并将RSF模型的结果与Cox模型的结果进行了比较。使用R软件(4.1.1版)分析数据。
    一个-,2-,3年生存率为74.5%,57.7%,48.6%,分别,中位生存期为59.0个月.前三个最重要的生存预测因子包括乳酸脱氢酶(LDH),绝对单核细胞计数(AMC),和白细胞(WBC)计数。高危患者的中位生存期仅为4.0个月。RSF模型的曲线下面积(AUC)在1年、2年和3年保持在0.90以上。RSF模型显示出比Cox模型(25.4%)更低的预测错误率(21.9%)。
    乳酸脱氢酶,AMC,WBC计数是HIV相关B细胞淋巴瘤患者最重要的预后预测因子。需要更大的前瞻性和/或多中心研究来验证此RSF模型。
    UNASSIGNED: There have been no reports about the application of random survival forest (RSF) model to predict disease progression of HIV-associated B-cell lymphoma.
    UNASSIGNED: A total of 44 patients with HIV-associated B-cell lymphoma who were referred to Nanjing Second Hospital from 2012 to 2019 were included. The RSF model was used to find predictors of survival, and the results of the RSF model were compared with those of the Cox model. The data were analyzed using R software (version 4.1.1).
    UNASSIGNED: One-, 2-, and 3-year survival rates were 74.5%, 57.7%, and 48.6%, respectively, and the median survival was 59.0 months. The first 3 most important predictors of survival included lactate dehydrogenase (LDH), absolute monocyte count (AMC), and white blood cells (WBCs) count. The median survival of high-risk patients was only 4.0 months. Areas under the curve (AUCs) of the RSF model remained at more than 0.90 at 1, 2, and 3 years. The RSF model displayed a lower prediction error rate (21.9%) than the Cox model (25.4%).
    UNASSIGNED: Lactate dehydrogenase, AMC, and WBCs count are the most important prognostic predictors for patients with HIV-associated B-cell lymphoma. Much larger prospective and/or multicentre studies are required to validtae this RSF model.
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  • 文章类型: Journal Article
    弓形虫是一种机会性病原体,可以侵入血脑屏障并仅在低炎症反应的情况下驻留在大脑中。当感染艾滋病毒时,免疫系统严重受损,导致潜伏弓形虫感染的重新激活,可以模仿中风的临床表现。我们报告了一例65岁的女性患者,她突然出现右肢体无力,行走困难,没有其他典型症状的麻木,怀疑急性缺血性中风。HIV血清学结果呈阳性,这加快了机会性感染的诊断工作。结合影像学检查和宏基因组学对脑脊液进行下一代测序,HIV相关的脑弓形体病得到证实。患者接受了弓形虫病和HIV的治疗。发病六个月后,患者可以独立行走,但仍表现出右上肢无力。在HIV感染患者中,脑弓形虫病,特别是表现为孤立的中风样发作,构成了更重大的挑战,强调需要进行更彻底的调查,以减少误诊的可能性。
    Toxoplasma gondii is an opportunistic pathogen that can intrude into the blood-brain barrier and reside in the brain only with low inflammatory reaction. When infected with HIV, the immune system becomes severely compromised and leads to the reactivation of latent toxoplasmosis infection, which can mimic the clinical manifestation of stroke. We report a case of a 65-year-old female patient who presented with sudden right limb weakness, walking difficulty, and numbness without other typical symptoms, raising suspicion of acute ischemic stroke. The HIV serology returned positive, which expedited the diagnostic workup for opportunistic infection. Combining imageological examination and metagenomics next-generation sequencing of cerebrospinal fluid, HIV-associated cerebral toxoplasmosis was confirmed. The patient underwent treatment for toxoplasmosis and HIV. Six months after onset, the patient can walk independently but still exhibits weakness in the right upper limb. In HIV-infected patients, cerebral toxoplasmosis, particularly presenting as isolated stroke-like episodes, poses a more significant challenge, emphasizing the need for more thorough investigations to reduce the potential for misdiagnosis.
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  • 文章类型: Journal Article
    背景:怀孕期间和产后期间的急性HIV感染增加了垂直传播的风险。世界卫生组织(世卫组织)建议对有感染艾滋病毒风险的孕妇和产后妇女进行暴露前预防。然而,在孕妇和产后妇女中,实际实践与实施暴露前预防的理想目标之间存在显著差距。因此,重要的是要确定是什么影响妇女在怀孕期间和产后实施暴露前预防。这篇综述旨在汇总孕妇和产后妇女实施暴露前预防的障碍和促进因素。
    方法:一系列电子数据库,包括PubMed,CINAHLPlus与全文,Embase,和WebofScience,进行了潜在相关的定性研究。搜索期从数据库的建立延长至2023年3月16日。这篇评论使用了ENTREQ(增强定性研究综合报告的透明度)声明来指导定性综合的设计和报告。使用JoannaBriggs研究所关键评估清单评估纳入研究的方法学质量。JBI元聚合方法用于指导数据提取,并应用JBIConQual方法指导综合证据水平的评估。
    结果:在检索到的2042项研究中,12符合纳入标准。总人口样本包括447名参与者,包括231名孕妇和产后妇女,21名男性伴侣,75名医疗保健提供者(HCP)/医疗保健工作者(HCWs),18个决策者,37位母亲和65名育龄妇女。共有149个结果的可信度等级为“明确”或“模棱两可”。暴露前预防实施的障碍和促进者被分为七类,包括三个促进者类别:感知利益,保持与合作伙伴的关系,和外部支持,和四个障碍:药物相关的障碍,污名,提供商和设施级别的障碍,和风险感知的偏见。
    结论:本系统综述和荟萃综合分析了孕妇和产后妇女实施暴露前预防的障碍和促进因素。我们汇总了产妇暴露前预防实施的几个障碍,包括药物相关因素,污名,提供商和设施级别的障碍,和风险感知偏见。因此,可以根据这些要点制定改善暴露前预防服务的干预措施。
    CRD42023412631。
    BACKGROUND: Acute HIV infection during pregnancy and in the postpartum period increases the risk of vertical transmission. The World Health Organization (WHO) has recommended preexposure prophylaxis for pregnant and postpartum women at risk of acquiring HIV. However, there are significant gaps between the actual practice and the ideal goal of preexposure prophylaxis implementation among pregnant and postpartum women. Therefore, it is important to determine what influences women\'s implementation of preexposure prophylaxis during pregnancy and in the postpartum period. This review aims to aggregate barriers and facilitators to preexposure prophylaxis implementation among pregnant and postpartum women.
    METHODS: A range of electronic databases, including PubMed, CINAHL Plus with Full Text, Embase, and Web of Science, were searched for potentially relevant qualitative studies. The search period extended from the establishment of the databases to March 16, 2023. This review used the ENTREQ (Enhancing transparency in reporting of qualitative research synthesis) statement to guide the design and reporting of qualitative synthesis. The methodological quality of the included studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. The JBI meta-aggregation method was applied for guiding the data extraction, and the JBI ConQual method was applied for guiding the evaluation of the level of evidence for the synthesis.
    RESULTS: Of retrieved 2042 studies, 12 met the inclusion criteria. The total population sample included 447 participants, including 231 pregnant and postpartum women, 21 male partners, 75 healthcare providers (HCPs)/healthcare workers (HCWs), 18 policymakers, 37 mothers, and 65 women of childbearing age. A total of 149 findings with credibility ratings of \"unequivocal\" or \"equivocal\" were included in this meta-synthesis. Barriers and facilitators to preexposure prophylaxis implementation were coded into seven categories, including three facilitator categories: perceived benefits, maintaining relationships with partners, and external support, and four barriers: medication-related barriers, stigma, barriers at the level of providers and facilities, and biases in risk perception.
    CONCLUSIONS: This systematic review and meta-synthesis aggregated the barriers and facilitators of preexposure prophylaxis implementation among pregnant and postpartum women. We aggregated several barriers to maternal preexposure prophylaxis implementation, including medication-related factors, stigma, barriers at the level of providers and facilities, and risk perception biases. Therefore, intervention measures for improving preexposure prophylaxis services can be developed based on these points.
    UNASSIGNED: CRD42023412631.
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  • 文章类型: Journal Article
    HIV-1复制在宿主细胞中受到严格调控,和各种限制因子在抑制病毒复制中具有重要作用。SAMHD1,一个众所周知的限制因素,通过水解细胞内dNTPs抑制HIV-1复制,从而限制了静止细胞中病毒cDNA的合成。在这项研究中,我们揭示了在病毒后cDNA合成阶段SAMHD1抑制的另一种独特机制。使用免疫沉淀和质谱分析,我们证明了SAMHD1和MX2/MxB之间的相互作用,干扰素诱导的抗病毒因子,抑制HIV-1cDNA核输入。内源性MX2表达的破坏显著削弱了SAMHD1抑制HIV-1的能力。已经鉴定了SAMHD1内与MX2结合的关键区域。值得注意的是,我们发现SAMHD1可以作为一个传感器,识别并结合传入的HIV-1核心,随后将其递送至由MX2形成的分子陷阱,从而阻断HIV-1核心结构的核进入。不能识别HIV-1核心的SAMHD1突变体显示出抗病毒活性的显著降低。HIV-1衣壳中的某些突变赋予对MX2抑制的抗性,同时维持对SAMHD1-MX2轴的抑制的易感性。总的来说,我们的研究确定了一个有趣的抗病毒模式,其中两个不同的限制因素,SAMHD1和MX2合作建立了一种偏离其行动的替代机制。这些发现为针对外源性病毒感染的复杂免疫防御网络提供了有价值的见解,并对靶向抗HIV疗法的开发具有意义。
    目的:与大多数直接与病毒成分结合以发挥其抗病毒作用的限制性因素相反,SAMHD1,真核生物中唯一已知的脱氧核苷酸三磷酸(dNTP)水解酶,通过减少可用于病毒cDNA合成的dNTP底物库来间接抑制静止细胞中的病毒复制。我们的研究为SAMHD1的抗病毒功能提供了新的视角。除了在dNTP水解中的作用外,SAMHD1与MX2合作抑制HIV-1核进口。在这个过程中,SAMHD1充当传入HIV-1核心的传感器,检测并结合它们,随后将复合物递送至由MX2形成的分子陷阱,从而固定病毒。这项研究不仅揭示了新的抗病毒途径SAMHD1,但也确定了一个独特的合作和两个不同的限制因素之间的相互作用。建立新的防御HIV-1感染的防线,这挑战了传统的制约因素独立行动的观点。总的来说,我们的发现进一步表明了宿主免疫防御网络的复杂性,并为促进宿主抗病毒免疫防御提供了潜在的靶点。
    HIV-1 replication is tightly regulated in host cells, and various restriction factors have important roles in inhibiting viral replication. SAMHD1, a well-known restriction factor, suppresses HIV-1 replication by hydrolyzing intracellular dNTPs, thereby limiting the synthesis of viral cDNA in quiescent cells. In this study, we revealed an additional and distinct mechanism of SAMHD1 inhibition during the postviral cDNA synthesis stage. Using immunoprecipitation and mass spectrometry analysis, we demonstrated the interaction between SAMHD1 and MX2/MxB, an interferon-induced antiviral factor that inhibits HIV-1 cDNA nuclear import. The disruption of endogenous MX2 expression significantly weakened the ability of SAMHD1 to inhibit HIV-1. The crucial region within SAMHD1 that binds to MX2 has been identified. Notably, we found that SAMHD1 can act as a sensor that recognizes and binds to the incoming HIV-1 core, subsequently delivering it to the molecular trap formed by MX2, thereby blocking the nuclear entry of the HIV-1 core structure. SAMHD1 mutants unable to recognize the HIV-1 core showed a substantial decrease in antiviral activity. Certain mutations in HIV-1 capsids confer resistance to MX2 inhibition while maintaining susceptibility to suppression by the SAMHD1-MX2 axis. Overall, our study identifies an intriguing antiviral pattern wherein two distinct restriction factors, SAMHD1 and MX2, collaborate to establish an alternative mechanism deviating from their actions. These findings provide valuable insight into the complex immune defense networks against exogenous viral infections and have implications for the development of targeted anti-HIV therapeutics.
    OBJECTIVE: In contrast to most restriction factors that directly bind to viral components to exert their antiviral effects, SAMHD1, the only known deoxynucleotide triphosphate (dNTP) hydrolase in eukaryotes, indirectly inhibits viral replication in quiescent cells by reducing the pool of dNTP substrates available for viral cDNA synthesis. Our study provides a novel perspective on the antiviral functions of SAMHD1. In addition to its role in dNTP hydrolysis, SAMHD1 cooperates with MX2 to inhibit HIV-1 nuclear import. In this process, SAMHD1 acts as a sensor for incoming HIV-1 cores, detecting and binding to them, before subsequently delivering the complex to the molecular trap formed by MX2, thereby immobilizing the virus. This study not only reveals a new antiviral pathway for SAMHD1 but also identifies a unique collaboration and interaction between two distinct restriction factors, establishing a novel line of defense against HIV-1 infection, which challenges the traditional view of restriction factors acting independently. Overall, our findings further indicate the intricate complexity of the host immune defense network and provide potential targets for promoting host antiviral immune defense.
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  • 文章类型: Journal Article
    人类免疫缺陷病毒(HIV)感染仍然是一个全球性的公共卫生问题,和开发有效的预防性疫苗诱导强效中和抗体仍然是一个重大的挑战。本研究旨在探讨与DNA/rTV疫苗诱导的中和抗体相关的炎症相关蛋白。在这项研究中,我们使用Olink芯片分析了接受HIV候选疫苗(DNA引发和重组牛痘病毒rTV增强)的健康个体血浆中的炎症相关蛋白,并比较了中和抗体阳性(nab+)和阴性(nab-)组之间的差异.我们确定了25个差异表达因子,并对其进行了富集和相关性分析。我们的结果表明,nab和-nab-组之间artemin(ARTN)和C-C基序趋化因子配体23(CCL23)的表达存在显着差异。值得注意的是,CCL23的表达与中和抗体的ID50和CD4+T细胞应答的强度呈负相关.本研究丰富了我们对DNA/rTV疫苗诱导的免疫图景的认识,并为未来的HIV疫苗开发提供见解。
    Human immunodeficiency virus (HIV) infection is still a global public health issue, and the development of an effective prophylactic vaccine inducing potent neutralizing antibodies remains a significant challenge. This study aims to explore the inflammation-related proteins associated with the neutralizing antibodies induced by the DNA/rTV vaccine. In this study, we employed the Olink chip to analyze the inflammation-related proteins in plasma in healthy individuals receiving HIV candidate vaccine (DNA priming and recombinant vaccinia virus rTV boosting) and compared the differences between neutralizing antibody-positive (nab + ) and -negative(nab-) groups. We identified 25 differentially expressed factors and conducted enrichment and correlation analysis on them. Our results revealed that significant expression differences in artemin (ARTN) and C-C motif chemokine ligand 23 (CCL23) between nab+ and -nab- groups. Notably, the expression of CCL23 was negatively corelated to the ID50 of neutralizing antibodies and the intensity of the CD4+ T cell responses. This study enriches our understanding of the immune picture induced by the DNA/rTV vaccine, and provides insights for future HIV vaccine development.
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  • 文章类型: Journal Article
    趋化因子受体4(CXCR4)是GPCR家族的一种亚型受体蛋白,具有七跨膜结构,广泛分布于人体组织中。CXCR4与疾病有关(例如,HIV-1感染),癌症增殖和转移,炎症信号通路,和白血病,使其成为有希望的药物靶标。关于CXCR4拮抗剂的临床试验主要集中在肽和抗体,有一些小分子化合物,如AMD11070(2)和MSX-122(3),在癌症治疗中显示出希望。本文讨论了CXCR4的构效关系(SAR)及其在疾病中的作用,主要关注CXCR4拮抗剂的SAR。它还探讨了不同疾病类别中CXCR4结合的标准结构特征和靶标相互作用。此外,它研究了各种修饰策略,以提出CXCR4药物有效性的潜在改善.
    Chemokine receptor 4 (CXCR4) is a subtype receptor protein of the GPCR family with a seven-transmembrane structure widely distributed in human tissues. CXCR4 is involved in diseases (e.g., HIV-1 infection), cancer proliferation and metastasis, inflammation signaling pathways, and leukemia, making it a promising drug target. Clinical trials on CXCR4 antagonists mainly focused on peptides and antibodies, with a few small molecule compounds, such as AMD11070 (2) and MSX-122 (3), showing promise in cancer treatment. This perspective discusses the structure-activity relationship (SAR) of CXCR4 and its role in diseases, mainly focusing on the SAR of CXCR4 antagonists. It also explores the standard structural features and target interactions of CXCR4 binding in different disease categories. Furthermore, it investigates various modification strategies to propose potential improvements in the effectiveness of CXCR4 drugs.
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