Newswise — New Brunswick, NJ — Scientists have discovered a molecular pathway that counteracts the ability of some viruses to evade the immune response. The research is newly published in Nature Immunology by researchers at Rutgers Robert Wood Johnson Medical School’s Child Health Institute of New Jersey and the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine. The team’s findings raise hope in generating better immune responses to viral infections, such as COVID-19, as well as to cancers which also develop strategies to evade immune recognition.

The goal of the immune system is to recognize and eliminate viruses and other pathogens before they cause disease. In the constant battle between viruses and their hosts, viruses often develop ways to thwart the immune response, replicate successfully, and result in illness. This is particularly true in viruses such as SARS-CoV-2, for which many people may be infected but never become sick, or herpes viruses which may establish latent, or quiet, states of infection.

This new research uncovered why some viruses are recognized and specifically eliminated by the immune system despite viral strategies to escape recognition. The study identified a new route that cell proteins, known as major histocompatibility complex of class I or MHC-I proteins, involved in recognizing viruses take to “rescue” recognition of foreign viral proteins even if the virus is trying evade the immune response. This rescue pathway is functional in cells that specialize in antigen presentation, the process that alerts the immune system to infections and also plays a role in determining if the immune system will react to cancer.

Gaëtan Barbet, PhD, a newly recruited assistant professor of pediatrics at the medical school’s Child Health Institute, has spent the past 16 years studying the biology of dendritic cells, macrophages and monocytes and how these antigen presenting cells orchestrate the immune response. Dr. Barbet is investigating how these cells shape the immune responses at mucosal surfaces in the body, like the lungs and gut. Dr. Barbet conducted this work with principal investigator Julie Magarian Blander, PhD, the Gladys and Roland Harriman Professor of Immunology in Medicine at the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine, and Priyanka Nair-Gupta, PhD, a former doctoral student in Dr. Blander’s lab.

“Some patients with an immunodeficiency disorder called Bare Lymphocyte Syndrome (BLS) have mutations in proteins, such as TAP, the transporter associated with antigen presentation, which is involved in recognizing viruses and other pathogens” says Dr. Barbet. “These results show that the immune system can use alternative routes, to recognize viruses, and could explain why some patients who have mutations in TAP are no more susceptible to viral infections than the rest of the population.”

“The idea of developing TAP-independent responses raises hope for multiple human diseases including cancer where MHC-I antigen-presenting functions often altered in tumor cells to evade the immune system,” adds Dr. Blander, who is an expert on innate immunity and inflammation. “Ultimately, we want to understand how to manipulate this TAP-independent response in order to better enhance anti-viral or anti-cancer responses or to better design vaccine strategies.”

The team’s research was supported in-part by funding from the National Institutes of Health, and the Crohn’s and Colitis Foundation. In addition to Dr. Blander, Dr. Nair-Gupta and Dr. Barbet, the group of investigators on this work included colleagues from Weill Cornell Medicine; the Icahn School of Medicine at Mount Sinai; New York University; and Goethe University, Frankfurt, Germany

Journal Link: Nature Immunology