HIV infection drives interferon signaling within intestinal SARS-CoV-2 target cells.
Rabiah Fardoos, Osaretin E Asowata, Nicholas Herbert, Sarah K Nyquist, Yenzekile Zungu, Alveera Singh, Abigail Ngoepe, Ian M Mbano, Ntombifuthi Mthabela, Dirhona Ramjit, Farina Karim, Warren Kuhn, Fusi G Madela, Vukani T Manzini, Frank Anderson, Bonnie Berger, Tune H Pers, Alex K Shalek, Alasdair Leslie, Henrik N Kløverpris
Author Information
Rabiah Fardoos: Africa Health Research Institute, Durban, South Africa.
Osaretin E Asowata: Africa Health Research Institute, Durban, South Africa.
Nicholas Herbert: Africa Health Research Institute, Durban, South Africa.
Sarah K Nyquist: Institute for Medical Engineering & Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.
Yenzekile Zungu: Africa Health Research Institute, Durban, South Africa.
Alveera Singh: Africa Health Research Institute, Durban, South Africa.
Abigail Ngoepe: Africa Health Research Institute, Durban, South Africa.
Ian M Mbano: Africa Health Research Institute, Durban, South Africa.
Ntombifuthi Mthabela: Africa Health Research Institute, Durban, South Africa.
Dirhona Ramjit: Africa Health Research Institute, Durban, South Africa.
Farina Karim: Africa Health Research Institute, Durban, South Africa.
Warren Kuhn: ENT Department, General Justice Gizenga Mpanza Regional Hospital (Stanger Hospital), University of KwaZulu-Natal, Durban, South Africa.
Fusi G Madela: Discipline of General Surgery, Inkosi Albert Luthuli Central Hospital, University of KwaZulu-Natal, Durban, South Africa.
Vukani T Manzini: Discipline of General Surgery, Inkosi Albert Luthuli Central Hospital, University of KwaZulu-Natal, Durban, South Africa.
Frank Anderson: Discipline of General Surgery, Inkosi Albert Luthuli Central Hospital, University of KwaZulu-Natal, Durban, South Africa.
Bonnie Berger: Computer Science and Artificial Intelligence Laboratory and Department of Mathematics, MIT, Cambridge, Massachusetts, USA.
Tune H Pers: Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Alex K Shalek: Institute for Medical Engineering & Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.
Alasdair Leslie: Africa Health Research Institute, Durban, South Africa.
Henrik N Kløverpris: Africa Health Research Institute, Durban, South Africa.
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.
