Host Genomics of the HIV-1 Reservoir Size and Its Decay Rate During Suppressive Antiretroviral Treatment,JAIDS: Journal of Acquired Immune Deficiency Syndromes

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Host Genomics of the HIV-1 Reservoir Size and Its Decay Rate During Suppressive Antiretroviral Treatment
JAIDS: Journal of Acquired Immune Deficiency Syndromes ( IF 2.9 ) Pub Date : 2020-12-01 , DOI: 10.1097/qai.0000000000002473
Christian W. Thorball ₁ , Alessandro Borghesi _{1,

2} , Nadine Bachmann _{3,

4} , Chantal Von Siebenthal _{3,

4} , Valentina Vongrad _{3,

4} , Teja Turk _{3,

4} , Kathrin Neumann _{3,

4} , Niko Beerenwinkel _{5,

6} , Jasmina Bogojeska ₇ , Volker Roth ₈ , Yik Lim Kok _{3,

4} , Sonali Parbhoo _{8,

9} , Mario Wieser ₈ , Jürg Böni ₄ , Matthieu Perreau ₁₀ , Thomas Klimkait ₁₁ , Sabine Yerly ₁₂ , Manuel Battegay ₁₃ , Andri Rauch ₁₄ , Patrick Schmid ₁₅ , Enos Bernasconi ₁₆ , Matthias Cavassini ₁₇ , Roger D. Kouyos _{3,

4} , Huldrych F. Günthard _{3,

4} , Karin J. Metzner _{3,

4} , Jacques Fellay _{1,

18} ,

Affiliation

School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland;
Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy;
Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland;
Institute of Medical Virology, University of Zurich, Zurich, Switzerland;
Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland;
SIB Swiss Institute of Bioinformatics, Basel, Switzerland;
IBM Research–Zurich, Rüschlikon, Switzerland;
Department of Mathematics and Computer Science, University of Basel, Basel, Switzerland;
Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA;
Division of Immunology and Allergy, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland;
Division Infection Diagnostics, Department Biomedicine—Petersplatz, University of Basel, Basel, Switzerland;
Division of Infectious Diseases and Laboratory of Virology, University Hospital Geneva, University of Geneva, Geneva, Switzerland;
Department of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland;
Department of Infectious Diseases, University Hospital Bern, Bern, Switzerland;
Division of Infectious Diseases, Cantonal Hospital of St. Gallen, St. Gallen, Switzerland;
Infectious Diseases Service, Regional Hospital of Lugano, Lugano, Switzerland;
Division of Infectious Diseases, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland; and
Precision Medicine Unit, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.

Background:

The primary hurdle for the eradication of HIV-1 is the establishment of a latent viral reservoir early after primary infection. Here, we investigated the potential influence of human genetic variation on the HIV-1 reservoir size and its decay rate during suppressive antiretroviral treatment.

Setting:

Genome-wide association study and exome sequencing study to look for host genetic determinants of HIV-1 reservoir measurements in patients enrolled in the Swiss HIV Cohort Study, a nation-wide prospective observational study.

Methods:

We measured total HIV-1 DNA in peripheral blood mononuclear cells from study participants, as a proxy for the reservoir size at 3 time points over a median of 5.4 years, and searched for associations between human genetic variation and 2 phenotypic readouts: the reservoir size at the first time point and its decay rate over the study period. We assessed the contribution of common genetic variants using genome-wide genotyping data from 797 patients with European ancestry enrolled in the Swiss HIV Cohort Study and searched for a potential impact of rare variants and exonic copy number variants using exome sequencing data generated in a subset of 194 study participants.

Results:

Genome-wide and exome-wide analyses did not reveal any significant association with the size of the HIV-1 reservoir or its decay rate on suppressive antiretroviral treatment.

Conclusions:

Our results point to a limited influence of human genetics on the size of the HIV-1 reservoir and its long-term dynamics in successfully treated individuals.

中文翻译：

抑制抗逆转录病毒治疗期间HIV-1储库大小及其衰减率的宿主基因组学。

背景：

消除HIV -1的主要障碍是在初次感染后尽早建立潜在的病毒库。在这里，我们调查了人类遗传变异对HIV -1储库大小及其在抑制性抗逆转录病毒治疗期间的衰变率的潜在影响。

设置：

全基因组关联研究和外显子组测序研究旨在寻找瑞士HIV队列研究（一项全国性前瞻性观察性研究）的患者中HIV -1储库测量的宿主遗传决定因素。

方法：

我们测量了研究参与者外周血单个核细胞中的总HIV -1 DNA，作为中值5.4年的3个时间点的储库大小的代表，并研究了人类遗传变异与2个表型读数之间的关联：储库大小研究期间的第一个时间点及其衰减率。我们使用来自瑞士HIV队列研究的797名欧洲血统患者的全基因组基因分型数据，对常见遗传变异的贡献进行了评估，并利用在一个子集中产生的外显子组测序数据，研究了罕见变异和外显子拷贝数变异的潜在影响。 194名研究参与者。