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HIV infection drives interferon signaling within intestinal SARS-CoV-2 target cells.
Fardoos, Rabiah; Asowata, Osaretin E; Herbert, Nicholas; Nyquist, Sarah K; Zungu, Yenzekile; Singh, Alveera; Ngoepe, Abigail; Mbano, Ian M; Mthabela, Ntombifuthi; Ramjit, Dirhona; Karim, Farina; Kuhn, Warren; Madela, Fusi G; Manzini, Vukani T; Anderson, Frank; Berger, Bonnie; Pers, Tune H; Shalek, Alex K; Leslie, Alasdair; Kløverpris, Henrik N.
  • Fardoos R; Africa Health Research Institute, Durban, South Africa.
  • Asowata OE; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
  • Herbert N; Africa Health Research Institute, Durban, South Africa.
  • Nyquist SK; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
  • Zungu Y; Africa Health Research Institute, Durban, South Africa.
  • Singh A; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
  • Ngoepe A; Institute for Medical Engineering & Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.
  • Mbano IM; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Mthabela N; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.
  • Ramjit D; Program in Computational and Systems Biology, MIT, Cambridge, Massachusetts, USA.
  • Karim F; Africa Health Research Institute, Durban, South Africa.
  • Kuhn W; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
  • Madela FG; Africa Health Research Institute, Durban, South Africa.
  • Manzini VT; Africa Health Research Institute, Durban, South Africa.
  • Anderson F; Africa Health Research Institute, Durban, South Africa.
  • Berger B; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
  • Pers TH; Africa Health Research Institute, Durban, South Africa.
  • Shalek AK; Africa Health Research Institute, Durban, South Africa.
  • Leslie A; Africa Health Research Institute, Durban, South Africa.
  • Kløverpris HN; ENT Department, General Justice Gizenga Mpanza Regional Hospital (Stanger Hospital), University of KwaZulu-Natal, Durban, South Africa.
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.
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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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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