Dr. Rongtuan Lin

Innate Immunity, Interferon Sginaling, Viral Evasion.

My laboratory focus on the molecular understanding of the positive and negative regulation of antiviral immunity and to manipulate the innate immune response as a therapeutic strategy to control virus infection and cancer. Virus infection is controlled in large part by the host antiviral immune response. In the past decade, our research, as well as the work of many others, has identified key elements of the immune system that sense and respond to incoming viruses. Currently, our research will focus on two major themes:

Given that viral RNA ligand-RIG-I interaction is the initial trigger of the innate and adaptive immune response, an attractive strategy for the development of an efficient and broad spectrum antiviral therapy to inhibit virus replication involves the use of natural or synthetic 5’pppRNAs that mimic the viral PAMPs to activate the innate host defense. We will investigate the potential of 5’pppRNA as a therapeutic antiviral agent against RNA virus infection and characterize RIG-I specific genes and the mechanisms responsible for the protective effect. 5’pppRNA mimics viral infection by binding to the same recognition receptor as viruses; it consequently triggers an immune response analogous to natural viral infection. Therefore, 5’pppRNA could be an excellent candidate for vaccine adjuvant. We will determine the ability of 5’pppRNA to boost the antiviral response as an adjuvant for vaccine development.

Recently we have demonstrated that antioxidant mechanisms play a key role in the regulation of the antiviral response. We will investigate the role and mechanisms of this pathway in potentiating viral infection and inhibition of the antiviral response. Our preliminary data demonstrate that a small molecule inhibitor of antioxidant pathway strongly inhibits Vesicular Stomatitis Virus (VSV) and Herpes simplex virus 1 infection. We will dissect the molecular mechanisms underlying this small molecule-mediated antiviral activity and evaluate its role in the control of neuropathic viral infections. Our ongoing study demonstrated that a small molecule activator of antioxidant pathway inhibits the innate immune response and potentiates VSV-mediated oncolysis in cancer cells. We will determine if enhancing VSV replication by this compound can be exploited by reducing cancer cell resistance to oncolytic viral therapy. Understanding these virus-host interactions will provide important insights concerning virus infection and disease.