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VGTI in the News

The Art of Self- Defence (Nature) (click to download)

Klaus Früh, Ph.D.

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), simian varicella virus (SVV), 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.

In addition, Früh and his colleagues are applying the tools of functional genomics – chemogenomics, transcriptomics, proteomics, interactomics and small interfering RNA - to search in a systematic fashion for host targets that are modified during infection by Dengue virus and related flaviruses such as West Nile Virus. 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.

These studies also contribute to the development of improved vaccine vectors as well as novel immunomodulatory therapies. A particular focus of this translational research is the development of CMV as a new vaccine vector, a joint effort with Louis Picker, Jay Nelson and Patrizia Caposio. CMV-vectors are unique in their ability to induce lifelong immunity against heterologous pathogens. Since CMV vectors provided unparalleled protection against simian immunodefiency virus (SIV), current efforts are directed towards developing CMV vectors as new prophylactic and therapeutic vaccines against AIDS. In this context, the Früh lab investigates the molecular mechanisms that allow CMV to overcome pre-existing immunity and establish secondary persistent infections. Additional research is directed towards increasing the safety while maintaining the immunogenicity of CMV vectored vaccines.

Biography
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.