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The Stereotypic Response of the Pulmonary Vasculature to Respiratory Viral Infections: Findings in Mouse Models of SARS-CoV-2, Influenza A and Gammaherpesvirus Infections


De Neck, Simon; Penrice-Randal, Rebekah; Clark, Jordan J; Sharma, Parul; Bentley, Eleanor G; Kirby, Adam; Mega, Daniele F; Han, Ximeng; Owen, Andrew; Hiscox, Julian A; Stewart, James P; Kipar, Anja (2023). The Stereotypic Response of the Pulmonary Vasculature to Respiratory Viral Infections: Findings in Mouse Models of SARS-CoV-2, Influenza A and Gammaherpesvirus Infections. Viruses, 15(8):1637.

Abstract

The respiratory system is the main target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 19 (COVID-19) where acute respiratory distress syndrome is considered the leading cause of death. Changes in pulmonary blood vessels, among which an endothelialitis/endotheliitis has been particularly emphasized, have been suggested to play a central role in the development of acute lung injury. Similar vascular changes are also observed in animal models of COVID-19. The present study aimed to determine whether the latter are specific for SARS-CoV-2 infection, investigating the vascular response in the lungs of mice infected with SARS-CoV-2 and other respiratory viruses (influenza A and murine gammaherpesvirus) by in situ approaches (histology, immunohistology, morphometry) combined with RNA sequencing and bioinformatic analysis. Non-selective recruitment of monocytes and T and B cells from larger muscular veins and arteries was observed with all viruses, matched by a comparable transcriptional response. There was no evidence of endothelial cell infection in any of the models. Both the morphological investigation and the transcriptomics approach support the interpretation that the lung vasculature in mice mounts a stereotypic response to alveolar and respiratory epithelial damage. This may have implications for the treatment and management of respiratory disease in humans.

Abstract

The respiratory system is the main target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 19 (COVID-19) where acute respiratory distress syndrome is considered the leading cause of death. Changes in pulmonary blood vessels, among which an endothelialitis/endotheliitis has been particularly emphasized, have been suggested to play a central role in the development of acute lung injury. Similar vascular changes are also observed in animal models of COVID-19. The present study aimed to determine whether the latter are specific for SARS-CoV-2 infection, investigating the vascular response in the lungs of mice infected with SARS-CoV-2 and other respiratory viruses (influenza A and murine gammaherpesvirus) by in situ approaches (histology, immunohistology, morphometry) combined with RNA sequencing and bioinformatic analysis. Non-selective recruitment of monocytes and T and B cells from larger muscular veins and arteries was observed with all viruses, matched by a comparable transcriptional response. There was no evidence of endothelial cell infection in any of the models. Both the morphological investigation and the transcriptomics approach support the interpretation that the lung vasculature in mice mounts a stereotypic response to alveolar and respiratory epithelial damage. This may have implications for the treatment and management of respiratory disease in humans.

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Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Veterinärwissenschaftliches Institut > Institute of Veterinary Pathology
Dewey Decimal Classification:570 Life sciences; biology
Scopus Subject Areas:Health Sciences > Infectious Diseases
Life Sciences > Virology
Uncontrolled Keywords:Virology, Infectious Diseases
Language:English
Date:27 July 2023
Deposited On:22 Nov 2023 09:03
Last Modified:29 Jun 2024 01:39
Publisher:MDPI Publishing
ISSN:1999-4915
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.3390/v15081637
PubMed ID:37631979
Other Identification Number:PMCID: PMC10458810
  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)