Mary Wilson
Well-known member
11 May 2022
DOI: 10.1126/sciadv.abm5371
Adam D. Kenney1,2, Stephanie L. Aron3, Clara Gilbert3, Naresh Kumar1, Peng Chen4, Adrian Eddy1,2, Lizhi Zhang1,2, Ashley Zani1,2, Nahara Vargas-Maldonado1, Samuel Speaks1,1,2 1,2 4 4 5 5 Jeffrey Kawahara , Parker J. Denz , Lisa Dorn , Federica Accornero , Jianjie Ma , Hua Zhu, Murugesan V. S. Rajaram1, Chuanxi Cai5, Ryan A. Langlois3, Jacob S. Yount1,2*
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.
https://www.science.org/doi/pdf/10.1126/sciadv.abm5371
DOI: 10.1126/sciadv.abm5371
Adam D. Kenney1,2, Stephanie L. Aron3, Clara Gilbert3, Naresh Kumar1, Peng Chen4, Adrian Eddy1,2, Lizhi Zhang1,2, Ashley Zani1,2, Nahara Vargas-Maldonado1, Samuel Speaks1,1,2 1,2 4 4 5 5 Jeffrey Kawahara , Parker J. Denz , Lisa Dorn , Federica Accornero , Jianjie Ma , Hua Zhu, Murugesan V. S. Rajaram1, Chuanxi Cai5, Ryan A. Langlois3, Jacob S. Yount1,2*
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.
https://www.science.org/doi/pdf/10.1126/sciadv.abm5371