HIV infection drives interferon signaling within intestinal SARS-CoV-2 target cells
Name
148920.2-20210816151034-covered-e0fd13ba177f913fd3156f593ead4cfd.pdf
Description
Published version
Size
2.82 MB
Format
Adobe PDF
Checksum (MD5)
152c34cd95f4036898bc32d91dec4fe9
Author(s)
Fardoos, Rabiah
Asowata, Osaretin E
Herbert, Nicholas
Nyquist, Sarah K
Zungu, Yenzekile
Singh, Alveera
Ngoepe, Abigail
Mbano, Ian M
Mthabela, Ntombifuthi
Ramjit, Dirhona
Date Issued
August 23, 2021
Journal
JCI Insight
Publisher
American Society for Clinical Investigation
Version
Final published version
Abstract
SARS-CoV-2 infects epithelial cells of the human gastrointestinal (GI) tract and causes related symptoms. HIV infection impairs gut homeostasis and is associated with an increased risk of COVID-19 fatality. To investigate the potential link between these observations, we analyzed single-cell transcriptional profiles and SARS-CoV-2 entry receptor expression across lymphoid and mucosal human tissue from chronically HIV-infected individuals and uninfected controls. Absorptive gut enterocytes displayed the highest coexpression of SARS-CoV-2 receptors ACE2, TMPRSS2, and TMPRSS4, of which ACE2 expression was associated with canonical interferon response and antiviral genes. Chronic treated HIV infection was associated with a clear antiviral response in gut enterocytes and, unexpectedly, with a substantial reduction of ACE2 and TMPRSS2 target cells. Gut tissue from SARS-CoV-2-infected individuals, however, showed abundant SARS-CoV-2 nucleocapsid protein in both the large and small intestine, including an HIV-coinfected individual. Thus, upregulation of antiviral response genes and downregulation of ACE2 and TMPRSS2 in the GI tract of HIV-infected individuals does not prevent SARS-CoV-2 infection in this compartment. The impact of these HIV-associated intestinal mucosal changes on SARS-CoV-2 infection dynamics, disease severity, and vaccine responses remains unclear and requires further investigation.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Chemistry
Koch Institute for Integrative Cancer Research at MIT
Ragon Institute of MGH, MIT and Harvard
Massachusetts Institute of Technology. Computational and Systems Biology Program
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Massachusetts Institute of Technology. Department of Mathematics
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1172/jci.insight.148920
