TGF-β1 increases viral burden and promotes HIV-1 latency in primary differentiated human bronchial epithelial cells

Abstract Combination antiretroviral therapy (cART) has increased the life expectancy of HIV patients. However, the incidence of non-AIDS associated lung comorbidities, such as COPD and asthma, and that of opportunistic lung infections have become more common among this population. HIV proteins secre...

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Autores principales: S. Chinnapaiyan, R. K. Dutta, M. Nair, H. S. Chand, I. Rahman, H. J. Unwalla
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Publicado: Nature Portfolio 2019
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Acceso en línea:https://doaj.org/article/834ec782dc1b4dcebf44bd65ff31e1a1
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spelling oai:doaj.org-article:834ec782dc1b4dcebf44bd65ff31e1a12021-12-02T15:08:20ZTGF-β1 increases viral burden and promotes HIV-1 latency in primary differentiated human bronchial epithelial cells10.1038/s41598-019-49056-62045-2322https://doaj.org/article/834ec782dc1b4dcebf44bd65ff31e1a12019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-49056-6https://doaj.org/toc/2045-2322Abstract Combination antiretroviral therapy (cART) has increased the life expectancy of HIV patients. However, the incidence of non-AIDS associated lung comorbidities, such as COPD and asthma, and that of opportunistic lung infections have become more common among this population. HIV proteins secreted by the anatomical HIV reservoirs can have both autocrine and paracrine effects contributing to the HIV-associated comorbidities. HIV has been recovered from cell-free bronchoalveolar lavage fluid, alveolar macrophages, and intrapulmonary lymphocytes. We have recently shown that ex-vivo cultured primary bronchial epithelial cells and the bronchial brushings from human subjects express canonical HIV receptors CD4, CCR5 and CXCR4 and can be infected with HIV. Together these studies suggest that the lung tissue can serve as an important reservoir for HIV. In this report, we show that TGF-β1 promotes HIV latency by upregulating a transcriptional repressor BLIMP-1. Furthermore, we identify miR-9-5p as an important intermediate in TGF-β-mediated BLIMP-1 upregulation and consequent HIV latency. The transcriptionally suppressed HIV can be reactivated by common latency reactivating agents. Together our data suggest that in patients with chronic airway diseases, TGF-β can elevate the HIV viral reservoir load that could further exacerbate the HIV associated lung comorbidities.S. ChinnapaiyanR. K. DuttaM. NairH. S. ChandI. RahmanH. J. UnwallaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
S. Chinnapaiyan
R. K. Dutta
M. Nair
H. S. Chand
I. Rahman
H. J. Unwalla
TGF-β1 increases viral burden and promotes HIV-1 latency in primary differentiated human bronchial epithelial cells
description Abstract Combination antiretroviral therapy (cART) has increased the life expectancy of HIV patients. However, the incidence of non-AIDS associated lung comorbidities, such as COPD and asthma, and that of opportunistic lung infections have become more common among this population. HIV proteins secreted by the anatomical HIV reservoirs can have both autocrine and paracrine effects contributing to the HIV-associated comorbidities. HIV has been recovered from cell-free bronchoalveolar lavage fluid, alveolar macrophages, and intrapulmonary lymphocytes. We have recently shown that ex-vivo cultured primary bronchial epithelial cells and the bronchial brushings from human subjects express canonical HIV receptors CD4, CCR5 and CXCR4 and can be infected with HIV. Together these studies suggest that the lung tissue can serve as an important reservoir for HIV. In this report, we show that TGF-β1 promotes HIV latency by upregulating a transcriptional repressor BLIMP-1. Furthermore, we identify miR-9-5p as an important intermediate in TGF-β-mediated BLIMP-1 upregulation and consequent HIV latency. The transcriptionally suppressed HIV can be reactivated by common latency reactivating agents. Together our data suggest that in patients with chronic airway diseases, TGF-β can elevate the HIV viral reservoir load that could further exacerbate the HIV associated lung comorbidities.
format article
author S. Chinnapaiyan
R. K. Dutta
M. Nair
H. S. Chand
I. Rahman
H. J. Unwalla
author_facet S. Chinnapaiyan
R. K. Dutta
M. Nair
H. S. Chand
I. Rahman
H. J. Unwalla
author_sort S. Chinnapaiyan
title TGF-β1 increases viral burden and promotes HIV-1 latency in primary differentiated human bronchial epithelial cells
title_short TGF-β1 increases viral burden and promotes HIV-1 latency in primary differentiated human bronchial epithelial cells
title_full TGF-β1 increases viral burden and promotes HIV-1 latency in primary differentiated human bronchial epithelial cells
title_fullStr TGF-β1 increases viral burden and promotes HIV-1 latency in primary differentiated human bronchial epithelial cells
title_full_unstemmed TGF-β1 increases viral burden and promotes HIV-1 latency in primary differentiated human bronchial epithelial cells
title_sort tgf-β1 increases viral burden and promotes hiv-1 latency in primary differentiated human bronchial epithelial cells
publisher Nature Portfolio
publishDate 2019
url https://doaj.org/article/834ec782dc1b4dcebf44bd65ff31e1a1
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