HIV Reprograms Human Airway Basal Stem/Progenitor Cells to Acquire a Tissue-Destructive Phenotype

Nancy P.Y. Chung, Xuemei Ou, K. M.Faisal Khan, Jacqueline Salit, Robert J. Kaner, Ronald Crystal

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

While highly active anti-retroviral therapy has dramatically improved the survival of HIV-infected individuals, there is an increased risk for other co-morbidities, such as COPD, manifesting as emphysema. Given that emphysema originates around the airways and that human airway basal cells (BCs) are adult airway stem/progenitor cells, we hypothesized that HIV reprograms BCs to a distinct phenotype that contributes to the development of emphysema. Our data indicate that HIV binds to but does not replicate in BCs. HIV binding to BCs induces them to acquire an invasive phenotype, mediated by upregulation of MMP-9 expression through activation of MAPK signaling pathways. This HIV-induced “destructive” phenotype may contribute to degradation of extracellular matrix and tissue damage relevant to the development of emphysema commonly seen in HIV+ individuals.

Original languageEnglish
Pages (from-to)1091-1100
Number of pages10
JournalCell Reports
Volume19
Issue number6
DOIs
Publication statusPublished - 9 May 2017
Externally publishedYes

Fingerprint

Stem cells
Stem Cells
Emphysema
HIV
Tissue
Phenotype
Matrix Metalloproteinases
Chemical activation
Cells
Degradation
Chronic Obstructive Pulmonary Disease
Extracellular Matrix
Up-Regulation
Morbidity
Survival

Keywords

  • airway basal stem/progenitor cells
  • HIV
  • matrix metalloproteinase-9
  • MMP-9
  • reprogramming

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

HIV Reprograms Human Airway Basal Stem/Progenitor Cells to Acquire a Tissue-Destructive Phenotype. / Chung, Nancy P.Y.; Ou, Xuemei; Khan, K. M.Faisal; Salit, Jacqueline; Kaner, Robert J.; Crystal, Ronald.

In: Cell Reports, Vol. 19, No. 6, 09.05.2017, p. 1091-1100.

Research output: Contribution to journalArticle

Chung, Nancy P.Y. ; Ou, Xuemei ; Khan, K. M.Faisal ; Salit, Jacqueline ; Kaner, Robert J. ; Crystal, Ronald. / HIV Reprograms Human Airway Basal Stem/Progenitor Cells to Acquire a Tissue-Destructive Phenotype. In: Cell Reports. 2017 ; Vol. 19, No. 6. pp. 1091-1100.
@article{8b1ef7d3c3774cf7a4121479bb224376,
title = "HIV Reprograms Human Airway Basal Stem/Progenitor Cells to Acquire a Tissue-Destructive Phenotype",
abstract = "While highly active anti-retroviral therapy has dramatically improved the survival of HIV-infected individuals, there is an increased risk for other co-morbidities, such as COPD, manifesting as emphysema. Given that emphysema originates around the airways and that human airway basal cells (BCs) are adult airway stem/progenitor cells, we hypothesized that HIV reprograms BCs to a distinct phenotype that contributes to the development of emphysema. Our data indicate that HIV binds to but does not replicate in BCs. HIV binding to BCs induces them to acquire an invasive phenotype, mediated by upregulation of MMP-9 expression through activation of MAPK signaling pathways. This HIV-induced “destructive” phenotype may contribute to degradation of extracellular matrix and tissue damage relevant to the development of emphysema commonly seen in HIV+ individuals.",
keywords = "airway basal stem/progenitor cells, HIV, matrix metalloproteinase-9, MMP-9, reprogramming",
author = "Chung, {Nancy P.Y.} and Xuemei Ou and Khan, {K. M.Faisal} and Jacqueline Salit and Kaner, {Robert J.} and Ronald Crystal",
year = "2017",
month = "5",
day = "9",
doi = "10.1016/j.celrep.2017.04.026",
language = "English",
volume = "19",
pages = "1091--1100",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "6",

}

TY - JOUR

T1 - HIV Reprograms Human Airway Basal Stem/Progenitor Cells to Acquire a Tissue-Destructive Phenotype

AU - Chung, Nancy P.Y.

AU - Ou, Xuemei

AU - Khan, K. M.Faisal

AU - Salit, Jacqueline

AU - Kaner, Robert J.

AU - Crystal, Ronald

PY - 2017/5/9

Y1 - 2017/5/9

N2 - While highly active anti-retroviral therapy has dramatically improved the survival of HIV-infected individuals, there is an increased risk for other co-morbidities, such as COPD, manifesting as emphysema. Given that emphysema originates around the airways and that human airway basal cells (BCs) are adult airway stem/progenitor cells, we hypothesized that HIV reprograms BCs to a distinct phenotype that contributes to the development of emphysema. Our data indicate that HIV binds to but does not replicate in BCs. HIV binding to BCs induces them to acquire an invasive phenotype, mediated by upregulation of MMP-9 expression through activation of MAPK signaling pathways. This HIV-induced “destructive” phenotype may contribute to degradation of extracellular matrix and tissue damage relevant to the development of emphysema commonly seen in HIV+ individuals.

AB - While highly active anti-retroviral therapy has dramatically improved the survival of HIV-infected individuals, there is an increased risk for other co-morbidities, such as COPD, manifesting as emphysema. Given that emphysema originates around the airways and that human airway basal cells (BCs) are adult airway stem/progenitor cells, we hypothesized that HIV reprograms BCs to a distinct phenotype that contributes to the development of emphysema. Our data indicate that HIV binds to but does not replicate in BCs. HIV binding to BCs induces them to acquire an invasive phenotype, mediated by upregulation of MMP-9 expression through activation of MAPK signaling pathways. This HIV-induced “destructive” phenotype may contribute to degradation of extracellular matrix and tissue damage relevant to the development of emphysema commonly seen in HIV+ individuals.

KW - airway basal stem/progenitor cells

KW - HIV

KW - matrix metalloproteinase-9

KW - MMP-9

KW - reprogramming

UR - http://www.scopus.com/inward/record.url?scp=85019184652&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019184652&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2017.04.026

DO - 10.1016/j.celrep.2017.04.026

M3 - Article

VL - 19

SP - 1091

EP - 1100

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 6

ER -