David M. Knipe

David M. Knipe
Born Lancaster, Ohio
Citizenship American
Nationality United States
Fields Virology
Microbiology
Immunobiology
Institutions Harvard Medical School
Alma mater Case Western Reserve University B.A.
Massachusetts Institute of Technology Ph.D.
University of Chicago Post-doctoral training
Known for Herpes simplex virus research
Fields Virology

David M. Knipe is the Higgins Professor of Microbiology and Molecular Genetics and interim Co-Chair in the Department of Microbiology and Immunobiology at the Harvard Medical School in Boston, Massachusetts[1] and co-chief editor of the reference book Fields Virology.[2] He had previously served as Chair of the Program in Virology at Harvard Medical School from 2004 through 2016.

Education

Knipe was educated at Case Western Reserve University, receiving a B.A. summa cum laude in biology in 1972. At CWRU, he conducted research with Dr. Robert D. Goldman and showed that microfilaments in mammalian cells were actin filaments through the binding of purified 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][5][6][7]

Following the completion of his graduate studies, he trained as post-doctoral fellow on molecular genetics of herpes simplex virus (HSV) 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.[8] This methodology was used to map viral glycoproteins, plaque morphology, and drug resistance markers, and to construct a genital herpes vaccine candidate.[9]

Research

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 HSV. He showed that HSV replicates its DNA in defined compartments in the infected cell nucleus.[10][11] They further showed that the viral genome associated with the nuclear lamina for immediate-early transcription. 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. This led to new areas 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.[12] He discovered the molecular basis of herpes simplex virus lytic and latent infection through the definition of epigenetic regulatory mechanisms in which: viral proteins promote euchromatin modifications on viral chromation and transcription of lytic genes in epithelial cells; and the viral latency-associated transcript promotes heterochromatin modifications on viral chromatin and silencing of lytic genes in neurons.[13][14][15] He defined the structure of viral chromatin during latent infection of neurons and the mechanisms by which viral DNA is kept silenced during latent infection.[16][17][18] He has also defined the cellular proteins that recognize herpesviral DNA in the nucleus and initiate innate signaling and restrict viral gene expression and identified viral proteins that block host innate responses.[19][20][21][22] His work has shown that replication-defective viruses can serve as a genital herpes vaccine and as a vaccine vector—one of these genital herpes vaccines is the leading candidate in phase I clinical trials.[9][23][24]

Awards and honors

Knipe has received several honors and awards including:

Personal life

Knipe is married to Suzanne Knipe; they have two daughters and three grandchildren.

References

  1. ↑ "Department of Microbiology and Immunobiology | Faculty and Their Research". Retrieved January 15, 2015.
  2. ↑ "Fields Virology". Retrieved January 15, 2015.
  3. ↑ Goldman, R. D.; Knipe, D. M. (1973). "Functions of Cytoplasmic fibers in non-muscle cell motility". Cold Spring Harbor Symposium on Quantitative Biology. 37: 523–534. doi:10.1101/sqb.1973.037.01.063.
  4. ↑ Knipe, D. M.; Lodish, H. F.; Baltimore, D. (1977). "Localization of two cellular forms of the vesicular stomatitis viral glycoprotein". Journal of Virology. 21 (3): 1121–1127. PMC 515653Freely accessible. PMID 191639.
  5. ↑ Knipe, D. M.; Baltimore, D.; Lodish, H. F. (1977). "Separate pathways of maturation of the major structural proteins of vesicular stomatitis virus". Journal of Virology. 21 (3): 1128–1139. PMC 515654Freely accessible. PMID 191640.
  6. ↑ Knipe, D. M.; Lodish, H. F.; Baltimore, D. (1977). "Analysis of the defects of temperature-sensitive mutants of vesicular stomatitis virus: intracellular degradation of specific viral proteins". Journal of Virology. 21 (3): 1140–1148. PMC 515655Freely accessible. PMID 191641.
  7. ↑ Knipe, D. M.; Baltimore, D.; Lodish, H. F. (1977). "Maturation of viral proteins in cells infected with temperature-sensitive mutants of vesicular stomatitis virus". Journal of Virology. 21 (3): 1149–1158. PMC 515656Freely accessible. PMID 191642.
  8. ↑ Knipe, D. M.; Ruyechan, W. T.; Roizman, B.; Halliburton, I. W. (1978). "Molecular genetics of herpes simplex virus: Demonstration of regions of obligatory and nonobligatory identity within diploid regions of the genome by sequence replacement and insertion". Proceedings of the National Academy of Sciences. 75 (8): 3896–3900. doi:10.1073/pnas.75.8.3896. ISSN 0027-8424.
  9. 1 2 Da Costa, X. J.; Jones, C. A.; Knipe, D. M. (1999). "Immunization against genital herpes with a vaccine virus that has defects in productive and latent infection". Proceedings of the National Academy of Sciences. 96 (12): 6994–6998. doi:10.1073/pnas.96.12.6994. ISSN 0027-8424.
  10. ↑ Quinlan, Margaret P.; Chen, Lan Bo; Knipe, David M. (1984). "The intranuclear location of a herpes simplex virus DNA-binding protein is determined by the status of viral DNA replication". Cell. 36 (4): 857–868. doi:10.1016/0092-8674(84)90035-7. ISSN 0092-8674.
  11. ↑ Kops, Anne de Bruyn; Knipe, David M. (1988). "Formation of DNA replication structures in herpes virus-infected cells requires a viral DNA binding protein". Cell. 55 (5): 857–868. doi:10.1016/0092-8674(88)90141-9. ISSN 0092-8674.
  12. ↑ Taylor, T. J.; Knipe, D. M. (2004). "Proteomics of Herpes Simplex Virus Replication Compartments: Association of Cellular DNA Replication, Repair, Recombination, and Chromatin Remodeling Proteins with ICP8". Journal of Virology. 78 (11): 5856–5866. doi:10.1128/JVI.78.11.5856-5866.2004. ISSN 0022-538X.
  13. ↑ Wang, Q.-Y.; Zhou, C.; Johnson, K. E.; Colgrove, R. C.; Coen, D. M.; Knipe, D. M. (2005). "Herpesviral latency-associated transcript gene promotes assembly of heterochromatin on viral lytic-gene promoters in latent infection". Proceedings of the National Academy of Sciences. 102 (44): 16055–16059. doi:10.1073/pnas.0505850102. ISSN 0027-8424.
  14. ↑ Cliffe, A. R.; Knipe, D. M. (2008). "Herpes Simplex Virus ICP0 Promotes both Histone Removal and Acetylation on Viral DNA during Lytic Infection". Journal of Virology. 82 (24): 12030–12038. doi:10.1128/JVI.01575-08. ISSN 0022-538X.
  15. ↑ Knipe, David M.; Cliffe, Anna (2008). "Chromatin control of herpes simplex virus lytic and latent infection". Nature Reviews Microbiology. 6 (3): 211–221. doi:10.1038/nrmicro1794. ISSN 1740-1526.
  16. ↑ Cliffe, A. R.; Garber, D. A.; Knipe, D. M. (2009). "Transcription of the Herpes Simplex Virus Latency-Associated Transcript Promotes the Formation of Facultative Heterochromatin on Lytic Promoters". Journal of Virology. 83 (16): 8182–8190. doi:10.1128/JVI.00712-09. ISSN 0022-538X.
  17. ↑ Cliffe, A. R.; Coen, D. M.; Knipe, D. M. (2013). "Kinetics of Facultative Heterochromatin and Polycomb Group Protein Association with the Herpes Simplex Viral Genome during Establishment of Latent Infection". mBio. 4 (1): e00590–12–e00590–12. doi:10.1128/mBio.00590-12. ISSN 2150-7511.
  18. ↑ Knipe, David M.; Lieberman, Paul M.; Jung, Jae U.; McBride, Alison A.; Morris, Kevin V.; Ott, Melanie; Margolis, David; Nieto, Amelia; Nevels, Michael; Parks, Robin J.; Kristie, Thomas M. (2013). "Snapshots: Chromatin control of viral infection". Virology. 435 (1): 141–156. doi:10.1016/j.virol.2012.09.023. ISSN 0042-6822.
  19. ↑ Orzalli, M. H.; DeLuca, N. A.; Knipe, D. M. (2012). "Nuclear IFI16 induction of IRF-3 signaling during herpesviral infection and degradation of IFI16 by the viral ICP0 protein". Proceedings of the National Academy of Sciences. 109 (44): E3008–E3017. doi:10.1073/pnas.1211302109. ISSN 0027-8424.
  20. ↑ Orzalli, M. H.; Conwell, S. E.; Berrios, C.; DeCaprio, J. A.; Knipe, D. M. (2013). "Nuclear interferon-inducible protein 16 promotes silencing of herpesviral and transfected DNA". Proceedings of the National Academy of Sciences. 110 (47): E4492–E4501. doi:10.1073/pnas.1316194110. ISSN 0027-8424.
  21. ↑ Orzalli, Megan H.; Knipe, David M. (2014). "Cellular Sensing of Viral DNA and Viral Evasion Mechanisms". Annual Review of Microbiology. 68 (1): 477–492. doi:10.1146/annurev-micro-091313-103409. ISSN 0066-4227.
  22. ↑ Orzalli, Megan H.; Broekema, Nicole M.; Diner, Benjamin A.; Hancks, Dustin C.; Elde, Nels C.; Cristea, Ileana M.; Knipe, David M. (2015). "cGAS-mediated stabilization of IFI16 promotes innate signaling during herpes simplex virus infection". Proceedings of the National Academy of Sciences. 112 (14): E1773–E1781. doi:10.1073/pnas.1424637112. ISSN 0027-8424.
  23. ↑ Dudek, T. E.; Torres-Lopez, E.; Crumpacker, C.; Knipe, D. M. (2011). "Evidence for Differences in Immunologic and Pathogenesis Properties of Herpes Simplex Virus 2 Strains From the United States and South Africa". Journal of Infectious Diseases. 203 (10): 1434–1441. doi:10.1093/infdis/jir047. ISSN 0022-1899.
  24. ↑ Knipe, David M.; Corey, Lawrence; Cohen, Jeffrey I.; Deal, Carolyn D. (2014). "Summary and recommendations from a National Institute of Allergy and Infectious Diseases (NIAID) workshop on "Next Generation Herpes Simplex Virus Vaccines"". Vaccine. 32 (14): 1561–1562. doi:10.1016/j.vaccine.2014.01.052. ISSN 0264-410X.
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