UCI-led study reveals how lung cells protect themselves against RNA viral infection

Newswise — Irvine, CA – February 22, 2023 - A new University of California, Irvine-led study uncovers how a protein, APOBEC3B, could protects cells against many different types of RNA viruses like respiratory syncytial virus (RSV), SARS-CoV2, influenza virus, poliovirus and measles, helping to prevent disease. The study was published in Nature Communications.

Titled, “APOBEC3B drives PKR-mediated translation shutdown and protects stress granules in response to viral infection,” the study findings provide an understanding of how lung cells, in particular, protect themselves against RNA viral infection. This new discovery is essential to developing future therapies to limit viral infection and improve the health of patients with chronic lung disease.

Respiratory syncytial virus (RSV), SARS-CoV2, influenza virus, poliovirus, and measles—all single-stranded RNA viruses—are some examples of highly contagious diseases transmitted by respiratory aerosols that commonly infect lung cells.

“Patients with chronic lung diseases, such as asthma, cystic fibrosis, chronic obstructive pulmonary disease and interstitial lung diseases, are more susceptible to respiratory lung infections. These viral infections can further contribute to disease progression,” said Remi Buisson, PhD, assistant professor in the UCI School of Medicine Department of Biological Chemistry. “An exciting part of our finding fills a critical knowledge gap by illuminating how APOBEC3B can promote innate immune responses in host cells without generating mutations in the virus genomes and promoting viral evolution.”

In this study, graduate students Lavanya Manjunath and Sunwoo Oh, both at UCI School of Medicine in the Buisson Laboratory, utilized different RNA virus models, including Sendai virus, poliovirus, and Sindbis virus as tools to determine how APOBEC3B regulates innate immune signaling in response to viral infection. Moreover, they found that APOBEC3B is recruited to stress granules through its interaction with PABPC1 to prevent stress granule destabilization and protect mRNAs associated with stress granules from an RNA endonuclease RNase L that cleave RNAs in host cells.

“We propose that APOBEC3B, in addition to its canonical role to edit viral genomes, functions with PABPC1 as important innate immunity mediators, protecting cells at different steps of the innate immune response against viral infections,” said Buisson. 

More research is needed to develop strategies to prevent RNA viral infection.

“Our next steps are to determine the detailed mechanism of how APOBEC3B recognizes viral genome to promote an innate immune response and prevent viral replication,” said Buisson. “The goal is to identify how RNA viruses developed resistance mechanisms to counteract APOBEC3B functions and escape host cell defense.” 

The study was funded by support from the National Institutes of Health.

About the UCI School of Medicine: Each year, the UCI School of Medicine educates more than 400 medical students, and nearly 150 doctoral and master’s students. More than 700 residents and fellows are trained at UCI Medical Center and affiliated institutions. The School of Medicine offers an MD; a dual MD/PhD medical scientist training program; and PhDs and master’s degrees in anatomy and neurobiology, biomedical sciences, genetic counseling, epidemiology, environmental health sciences, pathology, pharmacology, physiology and biophysics, and translational sciences. Medical students also may pursue an MD/MBA, an MD/master’s in public health, or an MD/master’s degree through one of three mission-based programs: the Health Education to Advance Leaders in Integrative Medicine (HEAL-IM), the Leadership Education to Advance Diversity-African, Black and Caribbean (LEAD-ABC), and the Program in Medical Education for the Latino Community (PRIME-LC). The UCI School of Medicine is accredited by the Liaison Committee on Medical Accreditation and ranks among the top 50 nationwide for research. For more information, visit som.uci.edu.