Fardoos, R;
Asowata, OE;
Herbert, N;
Nyquist, SK;
Zungu, Y;
Singh, A;
Ngoepe, A;
... Kløverpris, HN; + view all
(2021)
HIV infection drives interferon signaling within intestinal SARS-CoV-2 target cells.
JCI Insight
, 6
(16)
, Article e148920. 10.1172/jci.insight.148920.
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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 singlecell 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 HIVassociated intestinal mucosal changes on SARS-CoV-2 infection dynamics, disease severity, and vaccine responses remains unclear and requires further investigation.
| Type: | Article |
|---|---|
| Title: | HIV infection drives interferon signaling within intestinal SARS-CoV-2 target cells |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1172/jci.insight.148920 |
| Publisher version: | http://dx.doi.org/10.1172/jci.insight.148920 |
| Language: | English |
| Additional information: | © 2021, Fardoos et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10134360 |
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