HIV infection drives interferon signaling within intestinal SARS-CoV-2 target cells

Research output: Contribution to journalJournal articlepeer-review

Standard

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.

In: JCI insight, Vol. 6, No. 16, e148920, 2021.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Fardoos, R, Asowata, OE, Herbert, N, Nyquist, SK, Zungu, Y, Singh, A, Ngoepe, A, Mbano, IM, Mthabela, N, Ramjit, D, Karim, F, Kuhn, W, Madela, FG, Manzini, VT, Anderson, F, Berger, B, Pers, TH, Shalek, AK, Leslie, A & Kløverpris, HN 2021, 'HIV infection drives interferon signaling within intestinal SARS-CoV-2 target cells', JCI insight, vol. 6, no. 16, e148920. https://doi.org/10.1172/jci.insight.148920

APA

Fardoos, R., Asowata, O. E., Herbert, N., Nyquist, S. K., Zungu, Y., Singh, A., Ngoepe, A., Mbano, I. M., Mthabela, N., Ramjit, D., Karim, F., Kuhn, W., Madela, F. G., Manzini, V. T., Anderson, F., Berger, B., Pers, T. H., Shalek, A. K., Leslie, A., & Kløverpris, H. N. (2021). HIV infection drives interferon signaling within intestinal SARS-CoV-2 target cells. JCI insight, 6(16), [e148920]. https://doi.org/10.1172/jci.insight.148920

Vancouver

Fardoos R, Asowata OE, Herbert N, Nyquist SK, Zungu Y, Singh A et al. HIV infection drives interferon signaling within intestinal SARS-CoV-2 target cells. JCI insight. 2021;6(16). e148920. https://doi.org/10.1172/jci.insight.148920

Author

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. / HIV infection drives interferon signaling within intestinal SARS-CoV-2 target cells. In: JCI insight. 2021 ; Vol. 6, No. 16.

Bibtex

@article{19b81fcef2f74744a28a03261ea25d2f,
title = "HIV infection drives interferon signaling within intestinal SARS-CoV-2 target cells",
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. ",
author = "Rabiah Fardoos and Asowata, {Osaretin E.} and Nicholas Herbert and Nyquist, {Sarah K.} and Yenzekile Zungu and Alveera Singh and Abigail Ngoepe and Mbano, {Ian M.} and Ntombifuthi Mthabela and Dirhona Ramjit and Farina Karim and Warren Kuhn and Madela, {Fusi G.} and Manzini, {Vukani T.} and Frank Anderson and Bonnie Berger and Pers, {Tune H.} and Shalek, {Alex K.} and Alasdair Leslie and Kl{\o}verpris, {Henrik N.}",
note = "Funding Information: HNK is supported by the Wellcome Trust (202485/Z/16/Z). AL is supported by the Wellcome Trust (210662/Z/18/Z). This work was supported through the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative (grant DEL-15-006). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS) Alliance for Accelerating Excellence in Science in Africa and supported by the New Partnership for Africa{\textquoteright}s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (grant 107752/Z/15/Z) and the United Kingdom government. HNK and AS were supported by SANTHE. AKS was supported, in part, by the Searle Scholars Program, the Beckman Young Investigator Program, the NIH (5U24AI118672, 2R01HL095791, 2U19AI089992, 1R01HL134539, 1R01AI138546), a Sloan Fellowship in Chemistry, and the Bill and Melinda Gates Foundation. The views expressed in this publication are those of the authors and not necessarily those of AAS, NEPAD Agency, Wellcome Trust, or the United Kingdom government. Publisher Copyright: {\textcopyright} 2021, Fardoos et al.",
year = "2021",
doi = "10.1172/jci.insight.148920",
language = "English",
volume = "6",
journal = "JCI Insight",
issn = "2379-3708",
publisher = "American Society for Clinical Investigation",
number = "16",

}

RIS

TY - JOUR

T1 - HIV infection drives interferon signaling within intestinal SARS-CoV-2 target cells

AU - Fardoos, Rabiah

AU - Asowata, Osaretin E.

AU - Herbert, Nicholas

AU - Nyquist, Sarah K.

AU - Zungu, Yenzekile

AU - Singh, Alveera

AU - Ngoepe, Abigail

AU - Mbano, Ian M.

AU - Mthabela, Ntombifuthi

AU - Ramjit, Dirhona

AU - Karim, Farina

AU - Kuhn, Warren

AU - Madela, Fusi G.

AU - Manzini, Vukani T.

AU - Anderson, Frank

AU - Berger, Bonnie

AU - Pers, Tune H.

AU - Shalek, Alex K.

AU - Leslie, Alasdair

AU - Kløverpris, Henrik N.

N1 - Funding Information: HNK is supported by the Wellcome Trust (202485/Z/16/Z). AL is supported by the Wellcome Trust (210662/Z/18/Z). This work was supported through the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative (grant DEL-15-006). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS) Alliance for Accelerating Excellence in Science in Africa and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (grant 107752/Z/15/Z) and the United Kingdom government. HNK and AS were supported by SANTHE. AKS was supported, in part, by the Searle Scholars Program, the Beckman Young Investigator Program, the NIH (5U24AI118672, 2R01HL095791, 2U19AI089992, 1R01HL134539, 1R01AI138546), a Sloan Fellowship in Chemistry, and the Bill and Melinda Gates Foundation. The views expressed in this publication are those of the authors and not necessarily those of AAS, NEPAD Agency, Wellcome Trust, or the United Kingdom government. Publisher Copyright: © 2021, Fardoos et al.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1172/jci.insight.148920

DO - 10.1172/jci.insight.148920

M3 - Journal article

C2 - 34252054

AN - SCOPUS:85113353006

VL - 6

JO - JCI Insight

JF - JCI Insight

SN - 2379-3708

IS - 16

M1 - e148920

ER -

ID: 279195276