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

Josefsson, L and Palmer, S and Faria, NR and Lemey, P and Casazza, J and Ambrozak, D and Kearney, M and Shao, W and Kottilil, S and Sneller, M and Mellors, J and Coffin, JM and Maldarelli, F (2013) Single Cell Analysis of Lymph Node Tissue from HIV-1 Infected Patients Reveals that the Majority of CD4<sup>+</sup> T-cells Contain One HIV-1 DNA Molecule. PLoS Pathogens, 9 (6). ISSN 1553-7366

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Abstract

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.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Josefsson, L
Palmer, S
Faria, NR
Lemey, P
Casazza, J
Ambrozak, D
Kearney, M
Shao, W
Kottilil, S
Sneller, M
Mellors, Jjwm1@pitt.eduJWM1
Coffin, JM
Maldarelli, F
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorLuban, JeremyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 June 2013
Date Type: Publication
Journal or Publication Title: PLoS Pathogens
Volume: 9
Number: 6
DOI or Unique Handle: 10.1371/journal.ppat.1003432
Schools and Programs: School of Medicine > Medicine
Refereed: Yes
ISSN: 1553-7366
Date Deposited: 01 Jul 2014 16:20
Last Modified: 23 Jun 2021 22:55
URI: http://d-scholarship.pitt.edu/id/eprint/22125

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