Severin O. Gudima, Ph.D.

Assistant Professor
Microbiology, Molecular Genetics and Immunology

Ph.D., Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia, 1991


Publications: Click here

Office: 5031C Wahl Hall West | Lab: 5001/5031 Wahl Hall West
913-588-6995 | email

Currently positions are available for highly motivated graduate students and postdocs with experience in molecular virology to study pathogenesis and mechanism of infection of human hepatitis B virus (HBV) and human hepatitis delta virus (HDV).


Research Interests

Human hepatitis B virus (HBV) infection is a major health risk. There are approximately 400 million carriers of persistent infection worldwide, of whom about 1 million die annually from HBV-induced liver cancer and chronic liver disease. Co- or super-infection with the sub-viral agent hepatitis delta virus (HDV) can lead to more severe pathology, increasing liver damage and risk of cirrhosis and hepatocellular carcinoma (HCC). Recent estimates revealed that 53% of all HCC cases worldwide are related to HBV infection. HCC is the 5th most frequent cancer, but it remains the 3rd leading cause of cancer-related death after the lung and stomach cancer.

The research in my laboratory is aimed to ascertain molecular mechanism of HBV/HDV infection with emphasis on pathogenesis. The goal of the first ongoing study is to understand how the virus-induced pathogenesis is linked to a particular genotype of HBV. Data available strongly indicate that infection with different HBV genotypes can lead to substantially different levels of liver damage and corresponding progression of the disease. We plan to compare aspects of replication, assembly, and also infectivity in primary human hepatocytes (PHH) and certain determinants of the host response for all known 8 HBV genotypes. The finding of the most infectious HBV genotype will be of significant importance to the HBV field. It has a great potential for three major applications. The peptides derived from the N-terminus of the PreS1 domain of the large envelope protein, which belongs to the more infectious genotype, would be more potent antiviral inhibitors, more efficiently interacting with the receptor(s) and preventing HBV and HDV spread. If the more infectious genotype displayed the ability to infect the majority of PHH, than it would be possible to conduct the microarray studies using the in vitro infection system of PHH and examine the host response. Such studies now are not feasible, since currently in a best situation only about 20% of hepatocytes can be infected. The use of the more infectious HBV genotype can also result in the establishment of HBV-susceptible cell lines. This will seriously reduce the need for primary human hepatocytes, which so far represent the most adequate cells susceptible to HBV infection. Overall, this study will: (i) facilitate the understanding of the molecular mechanism of HBV genotype-specific pathogenesis; (ii) have a serious impact on the understanding of virus-host interactions; (iii) have the potential to advance the development of new generation of anti-HBV antiviral peptides.

The second study is set to delineate the significance of the balance between HBV and HDV for outcome of infection, as will it become transient or chronic with possible risk of liver cancer. It is proposed to quantitatively examine what regulates competition or homeostasis between the two viruses during co-assembly, since both viruses share the same envelope. Also, using cultures of PHH, the patterns of co- and super-infection will be analyzed, addressing if the two viruses compete for susceptible cells, and if their replication rates become mutually affected. We expect that the outcome of the second study will: (i) facilitate building the model of HBV-HDV homeostasis; (ii) improve the understanding of the mechanisms of HBV/HDV co-assembly, co-replication and co-infection; (iii) ascertain the significance of interference between HBV and HDV in relation to pathogenesis; and (iv) re-valuate aspects of re-infection in relation to mechanism of chronic infection.

Selected Publications

  • Gudima, S.O., Kazantseva, E.G., Kostuyk, D.A., Shchaveleva, I.L., Grishchenko, O.I., Memelova, L.V., Kochetkov, S.N. (1997) Deoxyribonucleotide-containing RNAs: a novel class of templates for HIV-1 reverse transcriptase. Nucl. Acids. Res. 25:4614-4618.
  • Gudima, S.O., K. Dingle, T.-T. Wu, Moraleda, G., Taylor, J. (1999) Characterization of the 5'-ends for polyadenylated RNAs synthesized during the replication of hepatitis delta virus.
    J. Virol. 73:6533-6539.
  • Gudima, S.O., Wu, S.-Y., Chiang, C.-M, Moraleda, G., Taylor, J. (2000) Origin of hepatitis delta virus mRNA. J. Virol. 74:7204-7210.
  • Chang, J., Moraleda, G., Gudima, S., Taylor, J. (2000) Efficient site-specific non-ribozyme opening on hepatitis delta virus genomic RNA in infected livers. J. Virol. 74:9889-9894.
  • Gudima, S., Chang, J., Moraleda, G., Azvolinsky, A., Taylor, J. (2002) Parameters of human hepatitis delta virus genome replication: the quantity, quality, and intracellular distribution of viral proteins and RNA. J. Virol. 76:3709-3719.
  • Gudima, S.O., Chang, J., and Taylor, J.M. (2004) Features affecting the ability of hepatitis delta virus RNAs to initiate RNA-directed RNA synthesis. J. Virol. 78:5737-5744.
  • Gudima, S.O., Chang, J., Taylor, J.M. (2005) Reconstitution in cultured cells of replicating HDV RNA from pairs of less than full-length RNAs. RNA 11:90-98.
  • Chang, J., Gudima, S.O., Tarn, C., Nie, X., Taylor, J.M. (2005) Development of a novel system to study hepatitis delta virus genome replication. J. Virol. 79:8182-8188.
  • Chang, J., Gudima, S.O., Taylor, J.M. (2005) Evolution of hepatitis delta virus RNA genome following long-term replication in cell culture. J. Virol. 79:13310-13316.
  • Chang, J, Nie, X., Gudima, S, Taylor, J. (2006) Replication of the hepatitis delta virus genome. In Recent Advances in RNA Virus Replication, ed. K.L. Hefferon, pp. 195-212.
  • Chang, J., Nie, X., Gudima, S., Taylor, J. (2006) Action of inhibitors on accumulation of processed hepatitis delta virus RNAs. J. Virol. 80:3205-3214.
  • Gudima, S.O., Chang, J., Taylor, J.M. (2006) Restoration in vivo, of defective hepatitis delta virus RNA genomes. RNA 12:1061-1073.
  • Gudima, S., He., Y., Meier, A., Chang, J., Chen, R., Jarnik, M., Nicolas, E., Bruss, V., Taylor, J. (2007) Assembly of hepatitis delta virus: particle characterization including ability to infect primary human hepatocytes. J. Virol. 81:3607-3617.
  • Gudima, S., Meier, A., Dunbrack, R., Taylor, J., Bruss, V. (2007) Two potentially important elements of the hepatitis B virus large envelope protein are dispensable for the infectivity of hepatitis delta virus. J. Virol. 81:4343-4347.
  • Chai, N., Gudima, S., Chang, J., Taylor, J. (2007) Immunoadhesins containing pre-S domains of hepatitis B virus large envelope protein are secreted and inhibit virus infection. J. Virol. 81:4912-4918.
  • Chai, N., Gudima, S., Chang, H, Chang, J, Taylor, J. (2007) Assembly of heptatitis B virus envelope proteins onto a lentivirus that infects primary human hepatocytes. J. Virol. 81:10897-10904.
  • Gudima, S., He, Y., Chai, N., Bruss, V., Urban S., Mason, W., Taylor, J. (2008) Primary human hepatocytes are susceptible to infection by hepatitis delta virus assembled with envelope proteins of woodchuck hepatitis virus. J. Virol. 82:7276-7283.
Last modified: May 16, 2014

Severin O. Gudima, Ph.D.

Contact

Severin O. Gudima, Ph.D.
Assistant Professor

5031C Wahl Hall West

P: (913) 588-6995
sgudima@kumc.edu

ID=x2721