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| Name |
Knipe, David M. |
| Location
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Harvard Medical School |
| Primary Field
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Microbial Biology |
| Secondary Field
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Genetics |
 Election Citation
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David Knipe studies the mechanisms by which DNA viruses infect cells and defy and manipulate the host epigenetic silencing mechanisms to undergo infection in different cell types.
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Research Interests
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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.
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