Viruses are masters at manipulating their host environment. Because they depend on host cells for their replication and on the host organism for their spread through the population, they have learned to manipulate the infected organism for their survival. The host, on the other hand, has developed highly efficient countermeasures against viral infection. In many cases a balance has been established; the host is able to control the viral pathogenicity but is unable to eradicate the virus, allowing it to continue infecting other individuals.
A prime example of this type of chronic infection under constant immune pressure is infection by viruses of the herpesvirus family. A large portion of the genomes of herpesviruses is devoted to changing the host environment of both the single host cell and the entire host organism. Klaus Früh and his staff have characterized several mechanisms in herpes simplex virus (HSV), human and rhesus cytomegalovirus (CMV) and Kaposi's sarcoma herpesvirus (KSHV) by which these viruses sabotage major antiviral pathways such as antigen presentation by histocompatibility-complex molecules or interferon-induced virus-tethering molecules. More recently, his also began studying how human-pathogenic poxviruses such as cowpox and monkeypox viruses evade stimulation of the adaptive cellular immune response by T lymphocytes. Zoonotic infection by these viruses are increasing due to waning anti-poxvirus immunity in endemic regions.
These studies involve the entire spectrum of modern molecular, cellular biology and biochemistry. In addition, Früh and his colleagues are applying the tools of functional genomics - DNA microarrays, mass-spectrometry, small interfering RNA - to search in a systematic fashion for host targets that are modified by virus infection. Applying these tools to in vitro systems that reflect important features of given viral infections, they identified novel host cell gene products that are crucial for viral survival or antiviral defense.
Because the importance of immune escape during a viral infection can't be studied in humans, Früh's team has begun analyzing the immune escape pathways of rhesus cytomegalovirus and monkeypox virus. The impact of mechanisms on viral pathogenesis is studied in animal models in collaboration with Louis Picker, Scott Wong and Mark Slifka. These studies will not only throw light on the importance of these viral immunomodulators for infection, but also contribute to the development of improved vaccine and gene therapy vectors as well as novel immunomodulatory therapies.
Klaus Früh received his Ph.D. from the University of Heidelberg in 1990. From 1991 to 1994 he was a postdoctoral scientist at the Scripps Research Institute in La Jolla, California. In 1994 he joined the R.W. Johnson Pharmaceutical Research Institute, where he directed the antiviral pharmaceutical research program. In 2000 he joined the OHSU Vaccine and Gene Therapy Institute as associate professor and ONPRC as associate scientist, at the same time becoming director of the Microarray Shared Resource. He was promoted to Professor and Senior Scientist in 2005.
Alzhanova, D., Edwards, D.M., Hammarlund, E., Scholz, I.G., Horst, D., Wagner, M.J., Upton, C., Wiertz, E.J., Slifka, M.K., and Früh, K. (2009). Cowpox virus inhibits Transporter associated with Antigen Processing to evade T cell recognition. Cell Host & Microbe in press.
Mansouri, M., Viswanathan, K., Douglas, J.L., Hines, J., Gustin, J., Moses, A.V., and Früh, K. (2009). Molecular mechanism of BST2/Tetherin downregulation by K5/MIR2 of Kaposi's sarcoma herpesvirus. J Virol, in press.
Hammarlund, E., Dasgupta, A., Pinilla, C., Norori, P., Früh, K., and Slifka, M.K. (2008). Monkeypox virus evades antiviral CD4+ and CD8+ T cell responses by suppressing cognate T cell activation. Proc Natl Acad Sci U S A 105, 14567-14572.
Mansouri, M., Rose, P.P., Moses, A.V., and Früh, K. (2008). Remodeling of endothelial adherens junctions by Kaposi's sarcoma-associated herpesvirus. J Virol 82, 9615-9628.
Powers, C.J., and Früh, K. (2008). Signal peptide-dependent inhibition of MHC class I heavy chain translation by rhesus cytomegalovirus. PLoS Pathog 4, e1000150.
Bartee, E., McCormack, A., and Früh, K. (2006). Quantitative membrane proteomics reveals new cellular targets of viral immune modulators. PLoS Pathog 2, e107.
See a full listing of Dr. Frueh's publications.