2024-03-28T08:47:02Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/133442022-11-10T14:47:22Zcom_20.500.12105_15322com_20.500.12105_2051com_20.500.12105_2152com_20.500.12105_2144com_20.500.12105_2145col_20.500.12105_16978col_20.500.12105_2153col_20.500.12105_2146
Repisalud
author
Filgueiras-Rama, David
author
Vasilijevic, Jasmina
author
Jalife, Jose
author
Noujaim, Sami F
author
Alfonso, Jose Manuel
author
Nicolas-Avila, Jose A.
author
Gutierrez, Celia
author
Zamarreño, Noelia
author
Hidalgo, Andres
author
Bernabe, Alejandro
author
Cop, Christopher Pablo
author
Ponce-Balbuena, Daniela
author
Guerrero-Serna, Guadalupe
author
Calle, Daniel
author
Desco, Manuel
author
Ruiz-Cabello, Jesus
author
Nieto, Amelia
author
Falcon, Ana
funder
Fundación La Caixa
funder
European Molecular Biology Organization
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Centro de Investigación Biomedica en Red - CIBER
funder
Fundación ProCNIC
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Frankel Cardiovascular Centre, Michigan Medicine (Estados Unidos)
funder
NIH - National Heart, Lung, and Blood Institute (NHLBI) (Estados Unidos)
2021-09-02T07:56:40Z
2021-09-02T07:56:40Z
2021-02
Cardiovasc Res. 2021; 117(3):876-89
1755-3245
http://hdl.handle.net/20.500.12105/13344
32346730
10.1093/cvr/cvaa117
Cardiovascular research
Human influenza A virus (hIAV) infection is associated with important cardiovascular complications, although cardiac infection pathophysiology is poorly understood. We aimed to study the ability of hIAV of different pathogenicity to infect the mouse heart, and establish the relationship between the infective capacity and the associated in vivo, cellular and molecular alterations.
We evaluated lung and heart viral titres in mice infected with either one of several hIAV strains inoculated intranasally. 3D reconstructions of infected cardiac tissue were used to identify viral proteins inside mouse cardiomyocytes, Purkinje cells, and cardiac vessels. Viral replication was measured in mouse cultured cardiomyocytes. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used to confirm infection and study underlying molecular alterations associated with the in vivo electrophysiological phenotype. Pathogenic and attenuated hIAV strains infected and replicated in cardiomyocytes, Purkinje cells, and hiPSC-CMs. The infection was also present in cardiac endothelial cells. Remarkably, lung viral titres did not statistically correlate with viral titres in the mouse heart. The highly pathogenic human recombinant virus PAmut showed faster replication, higher level of inflammatory cytokines in cardiac tissue and higher viral titres in cardiac HL-1 mouse cells and hiPSC-CMs compared with PB2mut-attenuated virus. Correspondingly, cardiac conduction alterations were especially pronounced in PAmut-infected mice, associated with high mortality rates, compared with PB2mut-infected animals. Consistently, connexin43 and NaV1.5 expression decreased acutely in hiPSC-CMs infected with PAmut virus. YEM1L protease also decreased more rapidly and to lower levels in PAmut-infected hiPSC-CMs compared with PB2mut-infected cells, consistent with mitochondrial dysfunction. Human IAV infection did not increase myocardial fibrosis at 4-day post-infection, although PAmut-infected mice showed an early increase in mRNAs expression of lysyl oxidase.
Human IAV can infect the heart and cardiac-specific conduction system, which may contribute to cardiac complications and premature death.
eng
Human influenza A virus causes myocardial and cardiac-specific conduction system infections associated with early inflammation and premature death.
journal article
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URL
https://repisalud.isciii.es/bitstream/20.500.12105/13344/1/HumanInfluenzaAVirus_2021.pdf
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URL
https://repisalud.isciii.es/bitstream/20.500.12105/13344/4/HumanInfluenzaAVirus_2021.pdf.txt
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HumanInfluenzaAVirus_2021.pdf.txt