PT  - JOURNAL ARTICLE
AU  - Dinesh Devadoss
AU  - Shashi P. Singh
AU  - Arpan Acharya
AU  - Kieu Chinh Do
AU  - Palsamy Periyasamy
AU  - Marko Manevski
AU  - Neerad Mishra
AU  - Carmen Tellez
AU  - Sundaram Ramakrishnan
AU  - Steve Belinsky
AU  - Siddappa Byrareddy
AU  - Shilpa Buch
AU  - Hitendra S. Chand
AU  - Mohan Sopori
TI  - Lung Bronchial Epithelial Cells are HIV Targets for Proviral Genomic Integration
AID  - 10.1101/2020.06.01.126821
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.06.01.126821
4099  - http://biorxiv.org/content/early/2020/06/01/2020.06.01.126821.short
4100  - http://biorxiv.org/content/early/2020/06/01/2020.06.01.126821.full
AB  - In the era of highly active anti-retroviral therapy (HAART), obstructive lung diseases (OLDs) are common among the people living with HIV (PLWH); however, the mechanism by which HIV induces OLDs is unclear. Although human bronchial epithelial cells (HBECs) express HIV coreceptors and are critical in regulating lung immune responses, their role in transmitting HIV remains unclear. Herein, we present evidence that HIV-1 infects normal HBECs and the viral DNA is integrated in the genome to establish the viral latency. To prove that HIV productively infects HBECs, we demonstrate: (a) along with CXCR4, HBECs express the HIV-receptor CD4, and are induced to express CCR5 by IL-13 treatment; (b) following infection with HIV, HBECs produce HIV-p24 and contain the latent HIV provirus, which is activated by endotoxin and/or vorinostat; (c) DNA from HIV-1 infected HBECs contains the HIV-specific gag and nef genes, along with Alu sequences, confirming the integration of HIV in the host DNA; (d) the lung epithelial cells of HIV-infected subjects and SHIV-infected cynomolgus macaques are positive for HIV-specific transcripts. Thus, these studies suggest that HIV establishes latency in lung epithelial cells, making them potential HIV reservoirs. The long-living lung epithelial cells, activated by commonly encountered lung infections, might represent an ideal HIV target/reservoir, contributing to OLDs and other HIV-associated lung comorbidities.Competing Interest StatementThe authors have declared no competing interest.