Single Cell Analysis of Lymph Node Tissue from HIV-1 Infected Patients Reveals that the Majority of CD4+ T-cells Contain One HIV-1 DNA Molecule

PLoS Pathogens

Sarah Palmer¹  Joseph Casazza¹  Mary Kearney²  Wei Shao²  Lina Josefsson³  Philippe Lemey³  John M. Coffin⁴  John Mellors⁴  Nuno R. Faria⁴  David Ambrozak⁴  Frank Maldarelli⁵  Shyamasundaran Kottilil⁶  Michael Sneller⁶ 

[1] Department of Diagnostics and Vaccinology, Swedish Institute for Communicable Disease Control, Solna, Sweden;Department of Microbiology and Immunology, Rega Institute, Katholieke Universiteit Leuven, Leuven, Belgium;Department of Microbiology, Tumor and Cell-biology, Karolinska Institutet, Solna, Sweden;HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Frederick, Maryland, United States of America;Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America;Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America

关键词: HIV-1;    T cells;    Lymph nodes;    Memory T cells;    Blood;    DNA recombination;    Blood plasma;    Microbial genetics;   

DOI  :  10.1371/journal.ppat.1003432

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Genetic recombination contributes to the diversity of human immunodeficiency virus (HIV-1). Productive HIV-1 recombination is, however, dependent on both the number of HIV-1 genomes per infected cell and the genetic relationship between these viral genomes. A detailed analysis of the number of proviruses and their genetic relationship in infected cells isolated from peripheral blood and tissue compartments is therefore important for understanding HIV-1 recombination, genetic diversity and the dynamics of HIV-1 infection. To address these issues, we used a previously developed single-cell sequencing technique to quantify and genetically characterize individual HIV-1 DNA molecules from single cells in lymph node tissue and peripheral blood. Analysis of memory and naïve CD4+ T cells from paired lymph node and peripheral blood samples from five untreated chronically infected patients revealed that the majority of these HIV-1-infected cells (>90%) contain only one copy of HIV-1 DNA, implying a limited potential for productive recombination in virus produced by these cells in these two compartments. Phylogenetic analysis revealed genetic similarity of HIV-1 DNA in memory and naïve CD4+ T-cells from lymph node, peripheral blood and HIV-1 RNA from plasma, implying exchange of virus and/or infected cells between these compartments in untreated chronic infection.

【 授权许可】

CC BY