Biosketch
David Knipe is a virologist recognized for his work on the mechanisms of herpesviral lytic and latent infection and foundational studies on viral epigenetics. In particular, his work on the mechanisms by which host cells attempt to epigenetically silence herpes simplex virus genomes and by which the virus manipulates those host responses to enable lytic versus latent infection have been fundamental in the field of viral epigenetics. Knipe was born in Lancaster, Ohio and grew up in rural Ohio. He received the BA degree in biology summa cum laude from Case Western Reserve University and the PhD degree in cell biology from Massachusetts Institute of Technology. His doctoral dissertation research with David Baltimore and Harvey Lodish defined the vesicular stomatitis viral mRNAs and the mechanisms of VSV membrane protein biosynthesis and localization. He was a postdoctoral fellow with Bernard Roizman at the University of Chicago, initiating his work on the molecular genetics of HSV. He has been a faculty member at Harvard Medical School since 1979 and is currently Higgins Professor of Microbiology and Head of the Virology Program. He is a member of the American Academy of Microbiology and the National Academy of Sciences.
Research Interests
David Knipe's laboratory is interested in the mechanisms by which DNA viruses infect cells and defy and manipulate the host epigenetic silencing mechanisms to undergo a lytic or latent infection in different cell types. Using herpes simplex virus, they have shown that the host cell loads the incoming HSV DNA genome with heterochromatin to silence it, but in non-neuronal cells the virus uses its proteins to reverse the silencing by degrading host restriction factors and shielding the replication process within nuclear replication compartments. The Knipe lab has defined three host restriction factors that serve to load or maintain heterochromatin on viral genomes and the mechanisms by which HSV blocks their activity. In sensory neurons the viral proteins cannot reverse the epigenetic silencing, and the viral latency-associated transcript, a long non-coding RNA, promotes facultative heterochromatin, so the viral genome is primed for reactivation. These studies have provided foundational work for the new field of viral epigenetics. Their understanding of the mechanisms of viral interactions with the host cell has also allowed them to design replication-defective mutant viruses that constitute a genital herpes vaccine in clinical trials and vaccine vectors and immunotherapeutic viruses in preclinical trials.
Membership Type
Member
Election Year
2021
Primary Section
Section 44: Microbial Biology
Secondary Section
Section 26: Genetics