tetano
Editor, Senior Moderator
Sci Adv
. 2022 May 13;8(19):eabm5371.
doi: 10.1126/sciadv.abm5371. Epub 2022 May 11.
Influenza virus replication in cardiomyocytes drives heart dysfunction and fibrosis
Adam D Kenney[SUP] 1 2 [/SUP], Stephanie L Aron[SUP] 3 [/SUP], Clara Gilbert[SUP] 3 [/SUP], Naresh Kumar[SUP] 1 [/SUP], Peng Chen[SUP] 4 [/SUP], Adrian Eddy[SUP] 1 2 [/SUP], Lizhi Zhang[SUP] 1 2 [/SUP], Ashley Zani[SUP] 1 2 [/SUP], Nahara Vargas-Maldonado[SUP] 1 [/SUP], Samuel Speaks[SUP] 1 [/SUP], Jeffrey Kawahara[SUP] 1 2 [/SUP], Parker J Denz[SUP] 1 2 [/SUP], Lisa Dorn[SUP] 4 [/SUP], Federica Accornero[SUP] 4 [/SUP], Jianjie Ma[SUP] 5 [/SUP], Hua Zhu[SUP] 5 [/SUP], Murugesan V S Rajaram[SUP] 1 [/SUP], Chuanxi Cai[SUP] 5 [/SUP], Ryan A Langlois[SUP] 3 [/SUP], Jacob S Yount[SUP] 1 2 [/SUP]
Affiliations
Abstract
Cardiac dysfunction is a common complication of severe influenza virus infection, but whether this occurs due to direct infection of cardiac tissue or indirectly through systemic lung inflammation remains unclear. To test the etiology of this aspect of influenza disease, we generated a novel recombinant heart-attenuated influenza virus via genome incorporation of target sequences for miRNAs expressed in cardiomyocytes. Compared with control virus, mice infected with miR-targeted virus had significantly reduced heart viral titers, confirming cardiac attenuation of viral replication. However, this virus was fully replicative in the lungs and induced similar systemic inflammation and weight loss compared to control virus. The miR-targeted virus induced fewer cardiac conduction irregularities and significantly less fibrosis in mice lacking interferon-induced transmembrane protein 3 (IFITM3), which serve as a model for influenza-associated cardiac pathology. We conclude that robust virus replication in the heart is required for pathology, even when lung inflammation is severe.
. 2022 May 13;8(19):eabm5371.
doi: 10.1126/sciadv.abm5371. Epub 2022 May 11.
Influenza virus replication in cardiomyocytes drives heart dysfunction and fibrosis
Adam D Kenney[SUP] 1 2 [/SUP], Stephanie L Aron[SUP] 3 [/SUP], Clara Gilbert[SUP] 3 [/SUP], Naresh Kumar[SUP] 1 [/SUP], Peng Chen[SUP] 4 [/SUP], Adrian Eddy[SUP] 1 2 [/SUP], Lizhi Zhang[SUP] 1 2 [/SUP], Ashley Zani[SUP] 1 2 [/SUP], Nahara Vargas-Maldonado[SUP] 1 [/SUP], Samuel Speaks[SUP] 1 [/SUP], Jeffrey Kawahara[SUP] 1 2 [/SUP], Parker J Denz[SUP] 1 2 [/SUP], Lisa Dorn[SUP] 4 [/SUP], Federica Accornero[SUP] 4 [/SUP], Jianjie Ma[SUP] 5 [/SUP], Hua Zhu[SUP] 5 [/SUP], Murugesan V S Rajaram[SUP] 1 [/SUP], Chuanxi Cai[SUP] 5 [/SUP], Ryan A Langlois[SUP] 3 [/SUP], Jacob S Yount[SUP] 1 2 [/SUP]
Affiliations
- PMID: 35544568
- DOI: 10.1126/sciadv.abm5371
Abstract
Cardiac dysfunction is a common complication of severe influenza virus infection, but whether this occurs due to direct infection of cardiac tissue or indirectly through systemic lung inflammation remains unclear. To test the etiology of this aspect of influenza disease, we generated a novel recombinant heart-attenuated influenza virus via genome incorporation of target sequences for miRNAs expressed in cardiomyocytes. Compared with control virus, mice infected with miR-targeted virus had significantly reduced heart viral titers, confirming cardiac attenuation of viral replication. However, this virus was fully replicative in the lungs and induced similar systemic inflammation and weight loss compared to control virus. The miR-targeted virus induced fewer cardiac conduction irregularities and significantly less fibrosis in mice lacking interferon-induced transmembrane protein 3 (IFITM3), which serve as a model for influenza-associated cardiac pathology. We conclude that robust virus replication in the heart is required for pathology, even when lung inflammation is severe.