Define Function of Viral Genome at Single Nucleotide Resolution

Speaker

Ren Sun
Professor
UCLA

Abstract

We have established a methodology to mutagenize every base pair of an entire viral genome and quantitatively monitor enrichment or diminishment of each genotype under specified growth conditions. The method enables generation of functional genomic maps under particular conditions (in vitro and in vivo) at a single nucleotide or single amino acid level. We have demonstrated the feasibility with four viruses: HIV, HCV, ZIKV and influenza virus. Recently we applying the method to simultaneously measured the replication fitness and interferon (IFN) sensitivity of mutations across the entire genome of influenza A virus. By incorporating eight IFN-sensitive mutations, we generated a Hyper Interferon Sensitive (HIS) virus as a vaccine candidate. HIS virus is highly attenuated in IFN-competent hosts but able to induce transient IFN responses, elicits robust humoral and cellular immune responses, and provides protection against homologous and heterologous viral challenges. 

In general, the method will accelerate the characterization of virus-host interactions, such as the interaction with each component of the host immune system. We are combining the high throughput genetic study with high resolution structural study to reveal the intricate molecular interactions. The systematic understanding of the viral fitness and structure will guide the rationale design of vaccine and anti-viral drugs. 

Biography

Dr. Ren Sun obtained his Bachelor of Science from Fudan University, Doctor of Philosophy in Molecular Biophysics and Biochemistry and postdoctoral training at Yale University. He joined the faculty of University of California at Los Angeles (UCLA) in 1997. Currently, he is a Distinguished Professor of Pharmacology at the David Geffen School of Medicine and Distinguished Professor of Bioengineering at Samueli School of Engineering. He has served as an Associate Dean of the medical school from 2007 to 2019. Currently he is the Associate Vice Provost for Internationalization at UCLA. 

Dr. Sun studies viruses that cause major health problems, including herpesviruses, influenza virus and HIV. He integrates genomics, immunology, molecular biology and structural biology to define the molecular mechanisms underlying viral replication to develop new vaccines.