Researchers are identifying pathways to fight the flu and the genes needed for immune protection against the flu

Researchers have identified the TDRD7 gene as a key regulator against the influenza A virus (IAV), which causes respiratory tract infections in 5 to 20 percent of the human population. These discoveries may contribute to the development of new therapeutic interventions against influenza virus infection. The study, conducted by the Icahn School of Medicine at Mount Sinai in collaboration with other institutions, was published in Achievements of science October 5.

IAV is responsible for 250,000-500,000 deaths per year worldwide. When IAV infects a host, an immunological response is initiated, consisting of a series of molecular processes. IAV can infect several different species, as well as physiological and genetic differences may contribute to different host responses among these species, although some responses are shared.

“Identifying key protective processes and key regulators in different species may facilitate the development of treatments for IAV in humans,” said Bin Zhang, Ph.D., director of the Center for Modeling Transformative Diseases, Willard Johnson Professor of Neurogenetics, and Mount Sinai’s Icahn Professor of Genetics and Genomic Sciences, who supervised the study.

The study used RNA sequencing for analysis gene expression over time in cells and tissues collected from IAV-infected humans, ferrets, and mice, identifying several key tissue- and species-specific defense processes. One gene that plays a key role in immunological defense mechanisms against IAV in all species was TDRD7, which encodes a Tudor domain-containing protein, a type of protein that has been shown to be involved in epigenetic regulation. In light of this discovery, the researchers conducted subsequent experiments to inhibit TDRD7 function, which resulted in increased viral replication in IAV-infected models.

“Determining both general and species-specific responses to influenza is essential for the development of effective treatments for influenza and may help further research into other respiratory infections such as COVID-19,” said Christian Forst, Ph.D., associate professor in the Department of Genetics and Genomic Sciences. , and microbiology, at Icahn Mount Sinai and first author of the study.