ACE2, TMPRSS2, and L-SIGN Expression in Placentae From HIV-Positive Pregnancies Exposed to Antiretroviral Therapy-Implications for SARS-CoV-2 Placental Infection.


Journal

The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675

Informations de publication

Date de publication:
08 Dec 2021
Historique:
pubmed: 22 4 2021
medline: 21 12 2021
entrez: 21 4 2021
Statut: ppublish

Résumé

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binding receptor ACE2 and the spike protein priming protease TMPRSS2 are coexpressed in human placentae. It is unknown whether their expression is altered in the context of HIV infection and antiretroviral therapy (ART). We compared mRNA levels of SARS-CoV-2 cell-entry mediators ACE2, TMPRSS2, and L-SIGN by quantitative polymerase chain reaction in 105 placentae: 45 from pregnant women with HIV (WHIV) on protease inhibitor (PI)-based ART, 17 from WHIV on non-PI-based ART, and 43 from HIV-uninfected women. ACE2 levels were lower, while L-SIGN levels were higher, in placentae from WHIV on PI-based ART compared to those on non-PI-based ART and to HIV-uninfected women. TMPRSS2 levels were similar between groups. Black race was significantly associated with lower expression of ACE2 and higher expression of L-SIGN. ACE2 levels were significantly higher in placentae of female fetuses. We identified pregnant women of black race and WHIV on PI-based ART to have relatively lower expression of placental ACE2 than those of white race and HIV-uninfected women. This may potentially contribute to altered susceptibility to COVID-19 in these women, favorably by reduced viral entry or detrimentally by loss of ACE2 protection against hyperinflammation.

Sections du résumé

BACKGROUND BACKGROUND
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binding receptor ACE2 and the spike protein priming protease TMPRSS2 are coexpressed in human placentae. It is unknown whether their expression is altered in the context of HIV infection and antiretroviral therapy (ART).
METHODS METHODS
We compared mRNA levels of SARS-CoV-2 cell-entry mediators ACE2, TMPRSS2, and L-SIGN by quantitative polymerase chain reaction in 105 placentae: 45 from pregnant women with HIV (WHIV) on protease inhibitor (PI)-based ART, 17 from WHIV on non-PI-based ART, and 43 from HIV-uninfected women.
RESULTS RESULTS
ACE2 levels were lower, while L-SIGN levels were higher, in placentae from WHIV on PI-based ART compared to those on non-PI-based ART and to HIV-uninfected women. TMPRSS2 levels were similar between groups. Black race was significantly associated with lower expression of ACE2 and higher expression of L-SIGN. ACE2 levels were significantly higher in placentae of female fetuses.
CONCLUSIONS CONCLUSIONS
We identified pregnant women of black race and WHIV on PI-based ART to have relatively lower expression of placental ACE2 than those of white race and HIV-uninfected women. This may potentially contribute to altered susceptibility to COVID-19 in these women, favorably by reduced viral entry or detrimentally by loss of ACE2 protection against hyperinflammation.

Identifiants

pubmed: 33880537
pii: 6242371
doi: 10.1093/infdis/jiab166
pmc: PMC8083191
doi:

Substances chimiques

CLEC4M protein, human 0
Cell Adhesion Molecules 0
HIV Protease Inhibitors 0
Lectins, C-Type 0
RNA, Messenger 0
Receptors, Cell Surface 0
Angiotensin-Converting Enzyme 2 EC 3.4.17.23
Serine Endopeptidases EC 3.4.21.-
TMPRSS2 protein, human EC 3.4.21.-

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

S631-S641

Subventions

Organisme : CIHR
ID : PJT148684
Pays : Canada

Informations de copyright

© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

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Auteurs

Smriti Kala (S)

Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.

Ksenia Meteleva (K)

Department of Immunology and Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.

Lena Serghides (L)

Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
Department of Immunology and Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada.

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