IMMUNOLOGICAL AND VIROLOGICAL EVENTS IN EARLY HIV INFECTION

HIV 感染早期的免疫学和病毒学事件

• 批准号: 8691648
• 负责人: JAMES Ivan MULLINS
• 金额: $ 246.27万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8691648
• 关键词: Acute; Antigens; Area; Biological; Biometry; Clinical; Couples; Data; Dimensions; Drug Formulations; Elements; Enrollment; Evaluation; Event; Evolution; Genetic; Goals; HIV; HIV Infections; HIV vaccine; HIV-1; Heterosexuals; Immune; Immune response; Immunity; Immunogenetics; Individual; Infection; Infection prevention; Leadership; Research Project Grants; Site; Technology; Therapeutic Intervention; Ursidae Family; Vaccines; Viral; Virus; Work; design; fitness; insight; pathogen; programs; repository; transmission process

DESCRIPTION (provided by applicant): The overriding goals of this competing renewal application are to understand the interactions between host immunity and viral replication, evolution and fitness, during and beyond acute HIV-1 infection. Our work is targeted to the goals of enhancing control and prevention of infection. The first 5 years of support for this work have been very productive, yielding important insight into early infection host-pathogen dynamics, the impact on viral fitness that occurs as a result of immune escape, the dynamics and cellular site of virus in HIV-1 exposed individuals that remain seronegative, therapeutic interventions, and the use of this data in the formulation of state-of-the-art vaccine immunogen designs. Our program is unique in that we focus on in-depth, multifaceted analysis of subjects that were enrolled while in acute HIV-1 B infection and then followed longitudinally for many years. Our additional foci on donor-recipient partner pairs and viral fitness represent state of the art leadership in these areas. In this renewal, we have added a new Project and the new dimension of evaluation of initially HIV-discordant couples and subsequent heterosexual transmission involving HIV-1 subtypes A, C and D. Our studies are critically important to the continuation of our growing understanding of primary HIV infection and to the design of protective HIV vaccines. State-of-the-art immunological, genetic and virologic technologies will be brought to bear to further dissect the biological mechanisms underlying host control, in three highly interactive research projects. Our Program is composed of three Projects that combine the areas of viral evolution and adaptation to host immunogenetics and cellular immune responses. We also have four Cores, covering the essential elements of Administration, Clinical, Virological and Repository, and Biostatistics functions.

描述（由申请人提供）：在急性HIV-1感染期间和之后，这种竞争性更新申请的重要目标是了解宿主免疫和病毒复制，进化和健身之间的相互作用。我们的工作针对增强感染控制和预防感染的目标。对这项工作的最初5年的支持非常有生产力，从而对早期感染宿主 - 病原体动力学进行了重要的见解，由于免疫逃生而对病毒适应性的影响，HIV-1中病毒的动力学和细胞部位发生的影响暴露的个体，这些个体仍然是血清神经，治疗性干预措施，以及该数据在制定最先进的疫苗免疫原设计中的使用。我们的计划是独一无二的，因为我们专注于对急性HIV-1 B感染期间入学的受试者的深入，多方面的分析，然后纵向进行了很多年。我们对捐助者伴侣对和病毒健身的额外重点代表了这些领域的艺术领导状况。在此续约中，我们添加了一个新项目以及对最初的HIV访问夫妇的评估以及随后涉及HIV-1亚型A，C和D的异性传播的新维度。我们的研究对我们对我们对我们对我们对日益了解的了解至关重要原发性HIV感染和保护性HIV疫苗的设计。在三个高度互动的研究项目中，将采用最先进的免疫，遗传和病毒学技术，以进一步剖析宿主控制的生物学机制。我们的计划由三个项目组成，这些项目结合了病毒进化和适应以托管免疫遗传学和细胞免疫反应。我们也有四个核心，涵盖了给药，临床，病毒学和存储库以及生物统计学功能的基本要素。

项目成果

Functional properties and epitope characteristics of T-cells recognizing natural HIV-1 variants.

T 细胞识别天然 HIV-1 变异体的功能特性和表位特征。

• DOI: 10.1016/j.vaccine.2009.08.093
• 发表时间: 2009
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: Malhotra,U;Nolin,J;Horton,H;Li,F;Corey,L;Mullins,JI;McElrath,MJ
• 通讯作者: McElrath,MJ

HIV Env conserved element DNA vaccine alters immunodominance in macaques.

• DOI: 10.1080/21645515.2017.1339852
• 发表时间: 2017-12-02
• 期刊: Human vaccines & immunotherapeutics
• 影响因子: 4.8
• 作者: Hu X;Valentin A;Rosati M;Manocheewa S;Alicea C;Chowdhury B;Bear J;Broderick KE;Sardesai NY;Gall SL;Mullins JI;Pavlakis GN;Felber BK
• 通讯作者: Felber BK

Broad and Gag-biased HIV-1 epitope repertoires are associated with lower viral loads.

• DOI: 10.1371/journal.pone.0001424
• 发表时间: 2008-01-09
• 期刊: PLOS ONE
• 影响因子: 3.7
• 作者: Rolland, Morgane;Heckerman, David;Deng, Wenjie;Rousseau, Christine M.;Coovadia, Hoosen;Bishop, Karen;Goulder, Philip J. R.;Walker, Bruce D.;Brander, Christian;Mullins, James I.
• 通讯作者: Mullins, James I.

A sensitive real-time PCR based assay to estimate the impact of amino acid substitutions on the competitive replication fitness of human immunodeficiency virus type 1 in cell culture.

• DOI: 10.1016/j.jviromet.2012.10.016
• 发表时间: 2013-04
• 期刊: Journal of virological methods
• 影响因子: 3.1
• 作者: Liu Y;Holte S;Rao U;McClure J;Konopa P;Swain JV;Lanxon-Cookson E;Kim M;Chen L;Mullins JI
• 通讯作者: Mullins JI

Lack of resistance to integrase inhibitors among antiretroviral-naive subjects with primary HIV-1 infection, 2007-2013.

• DOI: 10.3851/imp2780
• 发表时间: 2015
• 期刊: Antiviral therapy
• 影响因子: 1.2
• 作者: Stekler JD;McKernan J;Milne R;Tapia KA;Mykhalchenko K;Holte S;Maenza J;Stevens CE;Buskin SE;Mullins JI;Frenkel LM;Collier AC
• 通讯作者: Collier AC