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Severin O. Gudima, PhD

Severin Gudima portrait
Professor, Microbiology, Molecular Genetics and Immunology
sgudima@kumc.edu

Professional Background

Dr. Severin Gudima received extensive training in molecular biology and virology. He established his independent laboratory in the Department of Microbiology, Molecular Genetics and Immunology at KUMC in 2009. He is an internationally-recognized expert on human hepatitis B virus (HBV)/hepadnaviruses and human hepatitis delta virus (HDV), which is the sub-viral agent of the prototype hepadnavirus HBV that uses HBV envelope proteins (i.e., surface antigen of HBV, HBsAg) to form its virions and infect hepatocytes via HBV receptor. Both HBV and HDV remain significant human pathogens that can cause transient and chronic liver infections and inflict substantial liver pathogenesis, including chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC).


Research

Overview

My lab is working towards understanding (i) the mechanisms of HBV and HDV infections, (ii) determinants that are critical for maintenance of chronic infection state, and (iii) relationship between HBV and HDV infections and hepatocellular carcinoma (HCC). Since 2009, my lab made a number of significant findings that considerably advanced our understanding of the mechanisms regulating (i) chronic HBV and HDV infections, (ii) HBV-host, HDV-host and HBV-HDV interactions, and (iii) liver pathogenesis inflicted by either HBV or HDV.

Thus, we found that the cells of hepadnavirus-induced HCCs are susceptible in vivo to HDV infection.

We found that (i) the assembly and infectivity of HDV of genotype I can be fully supported by all HBV genotypes, and (ii) HBV envelope proteins were able to solely define both the number of HDV-infected hepatocytes and the number of HDV genomes that reached the nucleus post-entry and initiated HDV RNA genome replication.

We showed that fully functional HBV envelope proteins can be translated from HBV RNAs transcribed from HBV DNA that was naturally integrated into the human DNA, and these HBV envelope proteins can support the assembly of infectious HDV virions in the absence of ongoing HBV genome replication.

Using woodchucks chronically infected with WHV as the model of chronic HBV infection, we found that spread and super-infection of hepadnavirus continue during chronic infection and they are likely the important determinants of the maintenance of chronic hepadnavirus infection (including HBV).

We showed that HBV DNA integrant-derived RNAs (id-RNAs) can be considerably abundant as compared to HBV RNA species produced by HBV genome replication during chronic HBV infection in humans. Thus, id-RNAs may produce significant fraction of HBV envelope proteins (i.e., HBsAg) in cells bearing HBV DNA integrants, and thus can regulate the infectivity of HBV virions and their ability to support the virus spread and maintenance of chronic HBV infection, which calls for revision of the current model of HBV infection. It also became apparent that anti-HBV drugs fail to achieve loss of serum HBsAg in most cases, because major HBsAg amounts can be produced from id-RNAs regardless of HBV replication.

Using the woodchuck model of in vivo HDV infection, we showed that host "decides" if initial HDV infection will be cleared or it will become chronic by manipulating HDV properties, including its infectivity. Thus, if the infection will be cleared, HDV infectivity will be reduced to undetectable levels and the spread/super-infection will be blocked, but if infection becomes chronic, HDV infectivity will be considerable to support continuous spread/super-infection.