HIV infection drives interferon signaling within intestinal SARS-CoV-2 target cells.
JCI Insight
; 6(16)2021 08 23.
Article
in English
| MEDLINE | ID: covidwho-1369457
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Serine Endopeptidases
/
HIV Infections
/
Angiotensin-Converting Enzyme 2
/
SARS-CoV-2
/
Intestinal Mucosa
Type of study:
Observational study
/
Prognostic study
Topics:
Vaccines
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
Jci.insight.148920
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