Jacob S. Yount, PhD  Associate Professor Department of Microbial Infection and Immunity  The Ohio State University, College of Medicine Co-Director, Viruses and Emerging Pathogens Program OSU Infectious Diseases Institute

Some Influenza Complications May Be Due to Genetic Lack of an Immune Protein

MedicalResearch.com Interview with:

Jacob S. Yount, PhD  Associate Professor Department of Microbial Infection and Immunity  The Ohio State University, College of Medicine Co-Director, Viruses and Emerging Pathogens Program OSU Infectious Diseases Institute

Dr. Yount

Jacob S. Yount, PhD
Associate Professor
Department of Microbial Infection and Immunity
The Ohio State University, College of Medicine
Co-Director, Viruses and Emerging Pathogens Program
OSU Infectious Diseases Institute

MedicalResearch.com: What is the background for this study?

Response: Genetic defects in a human protein known as IFITM3 are linked to hospitalization and death upon influenza virus infections.  IFITM3 is an immune system protein that can inhibit virus entry into cells and it is produced as an early response to virus infections.  In order to better study the role of IFITM3 during infections, we engineered a mouse model that lacks this protein.  

MedicalResearch.com: What are the main findings? 

Response: We found that these mice are more susceptible to infection with every flu strain that we tested.  In addition, we found that when IFITM3 is lacking, virus can more readily disseminate from the lung to the heart and replicate to high levels in heart tissue.  This high virus load in the heart was accompanied by cardiac fibrosis and electrical dysfunction.  This is an important finding because heart complications of influenza virus infection are somewhat common in severe infections.

Our results suggest for the first time that IFITM3 deficiencies may underlie some of these complications and also provide one of the first animal models to be able to study infection of the heart by influenza virus.

MedicalResearch.com: What should readers take away from your report?

Response: There are complications of influenza virus infections beyond the standard respiratory infections that most people think of.  Possible infection of the heart is just one more reason to continue to research the basic biology of influenza virus infections. Further, it is one more reason that individuals should consider seasonal flu vaccination. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: Our IFITM3 deficient mouse model can now be used to better understand molecular pathways activated by influenza virus when it disseminates to the heart.  We can use this model to dissect how the virus induces cardiac fibrosis and how this might be prevented or treated.

MedicalResearch.com: Is there anything else you would like to add?

Response: This work was done in collaboration with several laboratories, including the cardiology laboratory of Dr. Murugesan Rajaram, who was a driving force for this work.  Dr. Rajaram also taught Adam Kenney, a PhD student who is the lead author of this work, how to perform EKGs on mice.

Citation: Adam D. Kenney, Temet M. McMichael, Alexander Imas, Nicholas M. Chesarino, Lizhi Zhang, Lisa E. Dorn, Qian Wu, Omar Alfaour, Foued Amari, Min Chen, Ashley Zani, Mahesh Chemudupati, Federica Accornero, Vincenzo Coppola, Murugesan V. S. Rajaram, Jacob S. Yount. IFITM3 protects the heart during influenza virus infection. Proceedings of the National Academy of Sciences, 2019; 201900784 DOI: 10.1073/pnas.1900784116

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Last Modified: Sep 10, 2019 @ 5:19 pm

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