UTMB researchers identify proteins that block immune response to COVID-19

Released October 6, 2020

Researchers from the The University of Texas Medical Branch at Galveston have discovered SARS-CoV-2 proteins that suppress the body’s immune response, thereby enabling infection and transmission of the disease.

The findings, recently published in the major research journal, Cell Reports, are paramount to understanding the biology of Covid-19 and to developing new vaccines against the disease.

“The outcome of any infection is determined by pathogen amplification and immune response inside our body. In the case of COVID patients, it is important to understand how SARS-CoV-2 replicates and how our immune system develops protective immunity, the two sides of the equation upon viral infection,” said Pei-Yong Shi, professor at Department of Biochemistry & Molecular Biology at UTMB. “In this study, we performed an unbiased screen of viral proteins from SARS-CoV-2 for their abilities to suppress interferon response. Such information is critical to understand how the virus shuts off host immune system to facilitate viral amplification in COVID-19 patients.”

“Interferon is the first line of defense when we encounter viral infection. We found that multiple viral proteins could suppress interferon production and signaling through different mechanisms,” said Hongjie Xia, the UTMB research scientist, senior co-author of the study.  “Our study has provided knowledge for new approaches for live-attenuated vaccine development. For example, we can now engineer mutant viruses that cannot suppress host immune response. Such mutant viruses could be used to prime our immune system as vaccine candidates. Since these mutant viruses could not fight against immune system, they would be rapidly eliminated by our immune response without causing disease.”

“The study also showed that the same proteins from different coronaviruses, such as SARS-CoV-2, MARS-CoV, and SARS-CoV-2, have different levels of potency in inhibiting interferon response. Such differences may partially account for distinct disease outcomes among various coronavirus infections,” said Vineet Menachery, assistant professor at UTMB, who collaborated on the study. “Future studies are needed to further evaluate the current findings in the context complete virus in infection animal models.”

“This is another example of collaborative team science at UTMB,” said Dr. Ben Raimer, president ad interim of UTMB. “The collective effort from multidisciplinary teams is essential to deliver this exciting study. UTMB will continue pursuing team science to translate the knowledge for development of new diagnosis, vaccine, and therapeutics.”

Other authrs include UTMB’s Zengguo, Xuping Xie, Xianwen Zhang, and John Yun-Chung Chen.

To implement this study, the UTMB team has received grants from National Institutes of Health and philanthropic support from the Sealy & Smith Foundation, the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation; the John S. Dunn Foundation; the Amon G. Carter Foundation; the Gillson Longenbaugh Foundation; the Summerfield G. Roberts Foundation.