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CD4 is expressed on a heterogeneous subset of hematopoietic progenitors,which persistently harbor CXCR4 and CCR5-tropic HIV proviral genomes in vivo
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نویسنده
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sebastian n.t. ,zaikos t.d. ,terry v. ,taschuk f. ,mcnamara l.a. ,onafuwa-nuga a. ,yucha r. ,signer r.a.j. ,riddell j. ,bixby d. ,markowitz n. ,morrison s.j. ,collins k.l.
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منبع
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plos pathogens - 2017 - دوره : 13 - شماره : 7
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چکیده
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Latent hiv infection of long-lived cells is a barrier to viral clearance. hematopoietic stem and progenitor cells are a heterogeneous population of cells,some of which are long-lived. cxcr4-tropic hivs infect a broad range of hspc subtypes,including hematopoietic stem cells,which are multi-potent and long-lived. however,ccr5-tropic hiv infection is limited to more differentiated progenitor cells with life spans that are less well understood. consistent with emerging data that restricted progenitor cells can be long-lived,we detected persistent hiv in restricted hspc populations from optimally treated people. further,genotypic and phenotypic analysis of amplified env alleles from donor samples indicated that both cxcr4- and ccr5-tropic viruses persisted in hspcs. rna profiling confirmed expression of hiv receptor rna in a pattern that was consistent with in vitro and in vivo results. in addition,we characterized a cd4highhspc sub-population that was preferentially targeted by a variety of cxcr4- and ccr5-tropic hivs in vitro. finally,we present strong evidence that hiv proviral genomes of both tropisms can be transmitted to cd4-negative daughter cells of multiple lineages in vivo. in some cases,the transmitted proviral genomes contained signature deletions that inactivated the virus,eliminating the possibility that coincidental infection explains the results. these data support a model in which both stem and non-stem cell progenitors serve as persistent reservoirs for cxcr4- and ccr5-tropic hiv proviral genomes that can be passed to daughter cells. © 2017 public library of science. all rights reserved.
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آدرس
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program in cellular and molecular biology,university of michigan,ann arbor,mi,united states,medical scientist training program,university of michigan,ann arbor,mi, United States, department of microbiology and immunology university of michigan,ann arbor,mi, United States, division of infectious disease,department of internal medicine university of michigan,ann arbor,mi, United States, division of infectious disease,department of internal medicine university of michigan,ann arbor,mi,united states,department of microbiology,university of pennsylvania school of medicine,philadelphia,pa, United States, department of microbiology and immunology university of michigan,ann arbor,mi,united states,division of bacterial diseases,national center for immunization and respiratory diseases,centers for disease control and prevention,atlanta,ga, United States, division of infectious disease,department of internal medicine university of michigan,ann arbor,mi, United States, division of infectious disease,department of internal medicine university of michigan,ann arbor,mi, United States, howard hughes medical institute,university of texas southwestern medical center,dallas,tx,united states,children’s research institute,university of texas southwestern medical center,dallas,tx,united states,department of pediatrics,university of texas southwestern medical center,dallas,tx,united states,division of regenerative medicine,department of medicine,moores cancer center,university of california,san diego,la jolla,ca, United States, iv,division of infectious disease,department of internal medicine university of michigan,ann arbor,mi, United States, division of oncology,department of internal medicine,university of michigan,ann arbor,mi, United States, division of infectious diseases,henry ford hospital,detroit,mi, United States, howard hughes medical institute,university of texas southwestern medical center,dallas,tx,united states,children’s research institute,university of texas southwestern medical center,dallas,tx,united states,department of pediatrics,university of texas southwestern medical center,dallas,tx, United States, program in cellular and molecular biology,university of michigan,ann arbor,mi,united states,medical scientist training program,university of michigan,ann arbor,mi,united states,department of microbiology and immunology university of michigan,ann arbor,mi,united states,division of infectious disease,department of internal medicine university of michigan,ann arbor,mi, United States
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Authors
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