Press Release

Influenza A Virus Discovered in Heart Muscle Tissue Causing Damage Long After It Has Cleared from the Lungs

Strategies to inhibit necrotic cell death or to prevent mitochondrial damage should be pursued as possible therapies to reduce cardiac damage during influenza infections

(Rockville, Maryland)—January 27, 2021—Scientists from the J. Craig Venter Institute (JCVI) have discovered that Influenza A virus (IAV) is found in heart tissue after it has been cleared from the lungs in mouse models. Live IAV present during convalescence does not actively replicate, preventing development of antiviral inflammatory responses, thus cloaking it from the immune system. Undetected, the virus continues to disrupt mitochondrial function, causing a metabolic breakdown and promoting cell death.

In response to the findings, senior author and JCVI assistant professor Norberto Gonzalez-Juarbe, Ph.D. stated, “Recent studies have pointed towards a direct link between influenza patients and later cardiac events, so we set out to try and understand the molecular mechanisms involved. While we expected to find myocardium (heart muscle) damage, we did not expect to find active IAV during convalescence.”

Wild-type and MLKL deficient mice—which lack the ability to undergo programmed necrosis, i.e. necroptosis—were infected with either the “2009 pandemic” strain or a laboratory Influenza A strain. The present study focused on the pandemic strain as previous clinical reports showed a higher rate of adverse cardiac events during each of the last influenza pandemics.

Once the infection had cleared the lungs, specimen heart tissue was analyzed using immunofluorescence microscopy and plaque assays which showed the presence of viable IAV particles in the myocardium. Further analysis on the global proteome and phosphoproteome was performed using mass spectrometry. This showed that both the proteome and phosphoproteome were significantly altered in IAV-infected mouse hearts, regardless of strain.

The proteome is the complete complement of proteins that can be expressed whereas the phosphoproteome is a subset of proteins that contain a phosphate group used in cell signaling networks. Disrupting cell signaling interferes with cellular function, metabolism, and immune responses.

The necroptosis deficient mice had increased survival and reduced weight loss post-IAV infection, as well as increased antioxidant and mitochondrial function, indicating partial protection to IAV infection. These observations suggest inhibition of necroptosis or prevention of mitochondrial damage as possible therapeutic interventions to reduce cardiac damage during influenza infections.

Given these findings, additional research is warranted on the effects of other pulmonary pandemic viruses on cardiac health. This is even more relevant given the current widespread observations of adverse cardiac events in COVID-19 patients.

Additional study participants include Dr. Peter H. Dube research group at The University of Texas Health Science Center at San Antonio.

The complete study, Influenza causes MLKL-driven cardiac proteome remodeling during convalescence, is found in the journal Circulation Research.

About J. Craig Venter Institute

The J. Craig Venter Institute (JCVI) is a not-for-profit research institute in Rockville, Maryland and La Jolla, California. dedicated to the advancement of the science of genomics; the understanding of its implications for society; and communication of those results to the scientific community, the public, and policymakers. Founded by J. Craig Venter, PhD, the JCVI is home to approximately 150 scientists and staff with expertise in human and evolutionary biology, genetics, bioinformatics/informatics, information technology, high-throughput DNA sequencing, genomic and environmental policy research, and public education in science and science policy. The JCVI is a 501(c)(3) organization. For additional information, please visit www.JCVI.org.

Media Contact

Matthew LaPointe, mlapointe@jcvi.org301-795-7918