University of Minnesota
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MICaB Faculty

Wade Bresnahan
Wade A. Bresnahan, Ph.D.

Associate Professor

Department of Microbiology

University of Texas Medical Branch, Galveston, 1997, Ph.D.

612-626-5876 office
612-626-5879 lab

E-mail:bresn013@umn.edu


Research Interests:

Molecular mechanisms of human cytomegalovirus replication and pathogenesis

My laboratory is focused on understanding the mechanisms of human cytomegalovirus (HCMV) replication and pathogenesis. The long term goal of my laboratory is to provide a molecular understanding of HCMV replication and pathogenesis that will lead to the development of novel approaches or therapeutics to help fight HCMV infection. HCMV is a ubiquitous herpesvirus that infects greater than 70% of the world’s population. Although HCMV infection is usually sub-clinical in healthy individuals, it is a major health problem for neonates, infants, and immunocompromised individuals. HCMV is the most common cause of viral induced birth defects in the US, with over 40,000 infants infected at birth each year. HCMV pathology in adults is most frequently encountered in immunocompromised individuals such as transplant recipients and AIDS patients. HCMV is the single most important infectious agent affecting organ transplant recipients; with at least two-thirds of these patients developing an HCMV-infection 1-4 months after transplantation. The increasing use of therapeutic immunosuppression, organ transplantation and the incidence of AIDS have focused our attention upon the HCMV life cycle, with a view towards achieving a thorough understanding of virus/cell interactions and viral replication processes, and thereby identifying approaches to attenuate primary and/or reactivated HCMV infection. Our research focuses on three areas of HCMV biology that include: 1) the identification and functional characterization of viral tegument proteins, 2) identifying the mechanisms by which HCMV subverts the host innate immune system, and 3) using genomic approaches to study HCMV gene regulation.

One major interest of our laboratory is to identify the mechanisms by which HCMV subverts the host’s innate antiviral defenses. Results from our laboratory indicate that HCMV rapidly and effectively blocks the induction of IFN-b and chemokines following infection of the host cell. The inhibition of IFN-b presumably inhibits the cells ability to induce interferon responsive genes and mount an effective antiviral response, thereby providing HCMV a mechanism to evade the host immune system and persist within the host. Using numerous biochemical and genetic approaches we have determined that the HCMV immediate early-2 gene product IE86 effectively blocks the induction of IFN-b and chemokines following HCMV infection. We are currently working to identify the molecular mechanism by which IE86 blocks the induction of these proteins.

A second interest in the laboratory involves determining what role HCMV tegument proteins play during HCMV replication. Tegument proteins are packaged within the virus particle and delivered to the host cell immediately upon infection. These tegument proteins are key regulators of viral and cellular gene expression, modulators of the host anti-viral response, and are critical for “kick starting” the viral infection. Our laboratory has taken biochemical and genetic approaches to decipher the functions of individual HCMV tegument proteins and examine what role they play in viral replication and pathogenesis

Selected Recent Publications:

  • Phillips, S.L., and W.A. Bresnahan. 2012. The human cytomegalovirus (HCMV) tegument protein UL94 is essential for secondary envelopment of HCMV virions. J. Virology, 86(5) 2523-2532.
  • Cygnar, D., S. Hagemeier, D. Kronemann, and W.A. Bresnahan. 2012. The cellular protein SPT6 is required for efficient replication of human cytomegalovirus. J. Virology. 86(4) 2011-2020.
  • Phillips, S.L., D. Cygnar, A. Thomas, and W.A. Bresnahan.  2012. Interaction between the human cytomegalovirus tegument proteins UL94 and UL99 is essential for virus replication. J. Virology, 86(18) 9995-10005.
  • Taylor, R.T., K.J. Lubick, S.J. Robertson, J.P. Broughton, M.E. Bloom, W.A. Bresnahan, and S.M. Best.  2011. TRIM79a, an interferon-stimulated gene product, restricts Tick-Borne Encephalitis virus replication by degrading the viral RNA polymerase. Cell Host and Microbe, 10(3) 185-196.
  • Phillips, S.L. and W.A. Bresnahan. 2011. Identification of binary interactions between human cytomegalovirus virion proteins. J. Virology, 85:440-7.
  • Kronneman, D., S.R. Hagemeier, D. Cygnar, S. Phillips, W.A. Bresnahan. 2010. Binding of the HCMV tegument protein UL69 to UAP56/URH49 is not required for efficient human cytomegalovirus replication. J. Virology. 84:9649-54.
  • DeFilippis, V.R., T. Sali, D. Alvarado, L. White, W.A. Bresnahan, and K. J. Fruh.  2010.  Human cytomegalovirus induces the interferon response via cytoplasmic dsDNA but not glycoprotein B.  J. Virology. 84:8913-25.
  • Taylor, R.T., and W.A. Bresnahan. 2006. Human Cytomegalovirus IE86 Attenuates Virus and TNFα-induced NFκB-Dependent Gene Expression. J. Virol. 80:10763-71.