Dr. Michael M.C. Lai @դh

Distinguished Research Fellow, IMB

Research

Molecular Biology and Pathogenesis of RNA Viruses

The primary research interests of my laboratory are the studies of the mechanisms of replication and pathogenesis of several medically important RNA viruses. My current interest is on four different viruses:

I. Coronavirus:

This virus family includes the SARS coronavirus, which causes severe acute respiratory syndrome. This virus contains the largest genome among RNA viruses. My laboratory has previously performed many pioneering studies on the structure and replication of this virus. We are currently focusing on studying the viral RNA replication processes regulated by viral ORF 1 proteins, and the functions of nonstructural protein (ORF8) of SARS coronavirus.

II. Hepatitis C virus (HCV):

This virus is one of the most common causes of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. My laboratory is interested in understanding the mechanism of viral RNA replication and pathogenesis. Currently we are focusing on studying the structure and mechanism of formation of the viral RNA replication complex, and identifying cellular factors involved in virus replication and pathogenesis. We are developing platform for screening antiviral agents.

III. Hepatitis delta virus (HDV):

This virus contains a small (1.7 kb) circular RNA genome, which is unique among animal viruses. It replicates by an RNA-dependent RNA replication mechanism via a rolling circle model, and yet it does not encode an RNA-dependent RNA polymerase (RdRP). Our recent findings showed that cellular DNA-dependent RNA polymerase II and polymerase I, together with a viral protein hepatitis delta antigen, carry out the different steps of HDV RNA replication. These observations suggest the capability of mammalian cells to perform RNA amplification even in the absence of RdRP. We are studying the roles of delta antigens on HDV RNA replication. Our recent findings showed that different post-translation forms of HDAg are required for the different steps of HDV RNA replication, suggesting a unique mechanism of regulation.

IV. Influenza A virus:

The genome of influenza A viruses consists of eight segments of single-stranded RNA with negative polarity that together encode 11 viral proteins. The interest in this virus was recently heightened by the outbreaks of avian influenza virus (H5N1) and potential threats of pandemic human influenza. To establish the capability of Taiwan scientific community to deal with the outbreaks of pandemic flu, we have launched the studies of influenza virus. We are establishing the reverse genetics system for the study of molecular biology of influenza viruses, particularly in focusing on the following issues: (i) conducting genetic studies to determine the roles of viral proteins/RNA sequences on viral replication or pathogenesis; (ii) studying virus-host interaction, to elucidate cellular factors involved in viral replication and pathogenesis; (iii). Studying the roles of modification of viral proteins on the biology of influenza A virus.