David M. Knipe

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David M. Knipe is the Higgins Professor of Microbiology and Molecular Genetics at the Harvard Medical School in Boston, Massachusetts^[1] and co-chief editor of the reference book Fields Virology.^[2]

Knipe has received several honors and awards including NIH Merit Award, Fellow of the American Academy of Microbiology, American Cancer Society Faculty Research Award,

Knipe was educated at Case Western Reserve University, receiving a B.A. summa cum laude in biology in 1972. He conducted research with Dr. Robert Goldman and showed that microfilaments in mammalian cells were actin filaments through the binding of heavy meromyosin to decorate the microfilaments in permeabilized cells.^[3] He continued his studies in cell biology at the Massachusetts Institute of Technology, earning his Ph.D. in 1976; his thesis research focused on vesicular stomatitis virus (VSV) under the supervision of Dr. David Baltimore and Dr. Harvey Lodish. Knipe first separated and translated the VSV mRNAs in vitro to identify their coding potential. He then showed that the VSV glycoprotein (G) and membrane (M) proteins are assembled into virions by two separate pathways. The pathway for G protein helped defined the secretory pathway for membrane glycoprotein assembly and the pathway for the M protein defined a cytosolic pathway for membrane protein assembly (4 JV papers).

Following the completion of his academic studies, he trained as post-doctoral fellow on molecular genetics of herpes simplex virus at the University of Chicago with Dr. Bernard Roizman. Knipe developed a cotransfection method for marker rescue mapping of mutations and introduction of new sequences into the HSV genome and showed that the ICP4 gene mapped in the repeated sequences of the short component of the viral genome.^[4] This methodology was used to map viral glycoproteins, plaque morphology, and drug resistance markers, and to construct a genital herpes vaccine candidate.^[5]

In 1979, Knipe joined the faculty at Harvard Medical School as an assistant professor of microbiology and molecular genetics and established his own lab to study herpes simplex viruses. He showed that HSV replicates its DNA in defined compartments in the infected cell nucleus.^[6][7] This work revealed that intranuclear proteins are localized to specific sites to carry out their functions, much as cytoplasmic proteins were known to localize to specific sites. . Led to new area of study of intranuclear compartmentalization of DNA virus replication. Knipe's research has shown that host cell DNA repair and recombination proteins are localized to the viral replication compartments and that some of these inhibit viral replication while some are essential for viral replication.^[8]

Showed that host factors could be sequestered in the nucleus away from host response genes in viral compartments so that host innate responses are inhibited.

Knipe defined the structure of viral chromatin during lytic and latent infection and developed a model for HSV latency in which chromatin plays an important role in whether HSV undergoes a lytic or latent infection in different cell types.

Defined the structure of the heterochromatin associated with the HSV genome during latent infection and showed that the HSV latency-associated transcript promotes the assembly of this heterochromatin on the viral genome, causing silencing of the viral genome in a form, facultative heterochromatin, that can be switched to euchromatin during reactivation.

Knipe first showed with Bob Finberg that replication-defective viral mutants could serve as a safe vaccine, by showing that HSV mutants could serve as a herpes vaccine (. Extended by others to adeno and pox viruses.