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Vincent Racaniello

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Vincent R. Racaniello
Born (1953-01-02) January 2, 1953 (age 71)
Paterson, New Jersey
Alma materCornell University (B.A.) (1974)
Mount Sinai Medical Center (Ph.D) (1980)
MIT (Post-doctoral)
Known forCD155 (poliovirus receptor, PVR)
Scientific career
FieldsMicrobiology
Immunology
Virology
InstitutionsColumbia University College of Physicians & Surgeons

Vincent R. Racaniello (born January 2, 1953) is a Higgins Professor in the Department of Microbiology and Immunology at Columbia University's College of Physicians and Surgeons.[1] He is a co-author of a textbook on virology, Principles of Virology.[2][3]

Racaniello has received the Irma T. Hirschl, Searle Scholars, Eli Lilly, Julius Youngner and NIH Merit awards. He has also been a Harvey Society Lecturer at Rockefeller University, the Hilleman Lecturer at the University of Chicago, and university lecturer at Columbia University. Spring of 2022, ETH Zurich awarded Racaniello the Richard R. Ernst award and lecture for his scientific communication work.[4] He was also the keynote speaker for the American Society for Virology, at its 2018 meeting.[5] Racaniello has served on the editorial boards of scientific journals, including the Journal of Virology,[6] and is a community editor for the open access journal PLOS Pathogens.[7] He also served as the 2015 president of the American Society for Virology.

Racaniello is the host of various podcasts, including This Week in Virology.

Early life and education

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Racaniello was born in Paterson, New Jersey. He graduated from Cornell University in 1974 (BA, biological sciences) and completed his PhD in the laboratory of Peter Palese in 1980,[8] studying genetic reassortment of influenza virus. As a post-doctoral fellow in David Baltimore's laboratory at the Massachusetts Institute of Technology (1979–1982), Racaniello used recombinant DNA technology to clone and sequence the genome of the small RNA animal virus poliovirus. Using these tools, he generated the first infectious clone of an animal RNA virus.[9] Construction of the infectious clone revolutionized modern virology.

Research

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Racaniello established his own research laboratory at Columbia University in the fall of 1982.[10] The aim of his laboratory is to understand replication and pathogenesis of small RNA animal viruses, picornaviruses. The reproductive cycle of a virus begins with its attachment to and entry into the cytoplasm of a cell. His laboratory identified CD155 (poliovirus receptor, PVR); a cell surface protein, and member of the immunoglobin superfamily as the protein that mediates this process.[11][12] Understanding how the interaction between virus and cell alters the viral particle and how virus entry is facilitated by the interaction has helped understand the means by which poliovirus infection is initiated.[13][14]

Humans are the only known natural host for poliovirus. The study of viral disease is therefore only feasible with the generation of a small animal model. Though not susceptible to poliovirus infection, murine cells do allow for efficient replication of poliovirus RNA introduced into the cytoplasm. Taking advantage of this observation, Racaniello's laboratory constructed the first small animal model of poliomyelitis. Mice producing the human CD155 protein were generated and infected with poliovirus.[15] These mice exhibited all symptoms and pathology of poliomyelitis observed in humans, including flaccid paralysis and spinal cord lesions. These mice today are used not only to continue to understand poliovirus pathogenesis but as a means to test the safety of stocks of the polio vaccine.

Poliomyelitis is a disease of the central nervous system; however, it is believed that CD155 is present on the surface of most if not all cells of the body. An element present within the virus RNA was hypothesized to govern viral tropism which tissues the virus infected. Newborn mice producing PVR were infected with wild-type poliovirus and a chimeric poliovirus in which this element was replaced with the same region from hepatitis C virus, a liver specific virus, or coxsackievirus B3, a virus that infects the heart or meninges. Mice infected with any of these viruses exhibited symptoms of poliomyelitis. Therefore, this region of poliovirus does not determine tissue tropism of the virus.[16]

Secretion of interferon is one means the body uses to ward off pathogens, including viral diseases. However, poliovirus is able to replicate when interferon is added to medium used to culture mammalian cells. Racaniello's laboratory believes that this resistance is dictated by the 2A protein of poliovirus.[17][18] Racaniello's laboratory continues to investigate how poliovirus circumvents the immune response of the host, enhancing our understanding of its pathogenesis and why it is a disease of the central nervous system.

Research after poliovirus

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Even though global eradication of poliovirus was initiated in 1988, and poliovirus infection continues throughout the world today, Racaniello's laboratory has begun to investigate the reproductive cycle and pathogenesis of other picornaviruses similar to poliovirus. These viruses include enteroviruses D68 (EV-D68) and 70 (EV70), human rhinovirus, coxsackievirus A21 and echovirus 1. Infectious clones of EV70 and several serotypes of rhinoviruses were generated.[19][20][21] These reagents have been used to understand how host range of a virus can be altered and to identify cellular proteins necessary for replication of the viral RNA. Racaniello has also begun to study how these viruses evade the host innate immune system, in particular interferon type I response. Infection of cultured cells with human rhinovirus 1A results in the cleavage of the integral component IPS-1 (MAVS, Cardif).[22] In addition a small animal model of virus echovirus 1 pathogenesis has been established.[23]

Racaniello is also interested in picornavirus evolution and movement. To this means, he intends to isolate and identify picornaviruses found in the wild throughout the Northeastern United States.

Racaniello's laboratory continues to pursue the fundamental principles of virus biology.[24] Together with a long-term collaborator, Racaniello's lab has determined that neurotropism of Zika virus and enterovirus D 68 are not a recently acquired phenotypes. Results from their studies examining Zika virus infection of the neonatal mouse brain revealed that cortical developmental pathologies associated with virus infection may result from architecture defects of the developing brain. Data from their research understanding the mechanism of enterovirus D68 associated acute flaccid myelitis suggests multiple means by which paralysis may result from virus infection.[25][26]

In collaboration with members of the Center for Infection and Immunology at Columbia, Rosenfeld and Racaniello described a cross-reactive anti-enterovirus antibody response.[27] These results challenge the idea that enterovirus infections are modulated solely by a homotypic humoral immune response.

Science beyond the laboratory

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Understanding that the World Wide Web is a primary scientific tool, Racaniello is one of the co-creators of BioCrowd,[28] a social network designed to bring together scientists of all disciplines. Racaniello's virology blog,[29] and podcasts This Week in Virology;[30] This Week in Parasitism[31] with colleagues Dickson Despommier and Daniel O. Griffin;[32] This Week in Microbiology[33] with Michelle Swanson, Michael Schmidt, Petra Levin and Elio Schaechter; This Week in Evolution[34] with Nels Elde;[35] Immune with Stephanie Langel, Brianne Barker and Cynthia Leifer;[36] and This Week in Neuroscience also unify science with technology. His blog, podcasts, specialized pages on Influenza 101[37] and Virology 101[38] aim to bring microbiology to non-scientists. Continuing to bring virology to those outside of the field, Racaniello established a library containing podcasts of lectures he has recently given at Columbia University.[39] He has also begun teaching virology via livestream on YouTube.[40] Additionally, every Wednesday evening with Amy Rosenfeld, Racaniello conducts a livestream "Q&A with A&V: Answering your COVID-19 questions".[41] He also has a new weekly livestream show "Office Hours with Earth's Virology Professor".[42]

Patents

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Racaniello is listed as inventor on at least 12 patents.[43]

References

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  1. ^ "Department of Microbiology and Immunology at Columbia University's College of Physicians and Surgeons".
  2. ^ S. J. Flint L.; V. R. Racaniello; G.F. Rall; A.M. Skalka (August 2015). Principles of Animal Virology - 4th Edition. ASM Press. ISBN 978-1-55581-443-4.
  3. ^ "This Week in Virology". TWiV 662: Principals of Principles, Fifth Edition. 11 September 2020. Retrieved 16 September 2020.
  4. ^ "Richard R Ernst".
  5. ^ "Asv 2018".
  6. ^ "Journal of Virology". American Society for Microbiology. Retrieved 22 August 2014.
  7. ^ "PLOS Pathogens". PLOS. Retrieved 22 August 2014.
  8. ^ "Palese Laboratory". Icahn School of Medicine at Mount Sinai. Retrieved 22 August 2014.
  9. ^ Racaniello, Vincent R.; David Baltimore (1981-11-20). "Cloned Poliovirus Complementary DNA is Infectious in Mammalian Cells". Science. New Series. 214 (4523): 916–919. Bibcode:1981Sci...214..916R. doi:10.1126/science.6272391. JSTOR 1686330. PMID 6272391.
  10. ^ "Vincent Racaniello, Ph.D." Columbia Faculty Profile: Vincent Racaniello. Department of Microbiology & Immunology, Columbia University. Retrieved 22 August 2014.
  11. ^ Mendelsohn, Cathy; Barbara Johnson; Kathryn Ann Lionetti; Peter Nobis; Eckard Wimmer; Vincent R. Racaniello (1986-10-15). "Transformation of a Human Poliovirus Receptor Gene into Mouse Cells". Proceedings of the National Academy of Sciences of the United States of America. 83 (20): 7845–7849. Bibcode:1986PNAS...83.7845M. doi:10.1073/pnas.83.20.7845. JSTOR 28192. PMC 386819. PMID 3020560.
  12. ^ Mendelsohn, Cathy L; Eckard Wimmer; Vincent R Racaniello (1989). "Cellular receptor for poliovirus: molecular cloning, nucleotide sequence, and expression of a new member of the immunoglobulin superfamily". Cell. 56 (5): 855–865. doi:10.1016/0092-8674(89)90690-9. PMID 2538245. S2CID 44296539.
  13. ^ Tsang, S. K.; B. M. McDermott; V. R. Racaniello; J. M. Hogle (2001-06-01). "Kinetic Analysis of the Effect of Poliovirus Receptor on Viral Uncoating: the Receptor as a Catalyst". Journal of Virology. 75 (11): 4984–4989. doi:10.1128/JVI.75.11.4984-4989.2001. ISSN 0022-538X. PMC 114901. PMID 11333877.
  14. ^ McDermott, B. M.; A. H. Rux; R. J. Eisenberg; G. H. Cohen; V. R. Racaniello (2000-07-28). "Two Distinct Binding Affinities of Poliovirus for Its Cellular Receptor". Journal of Biological Chemistry. 275 (30): 23089–23096. doi:10.1074/jbc.M002146200. PMID 10770940.
  15. ^ Ren, R. B.; F. Costantini; E. J. Gorgacz; J. J. Lee; V. R. Racaniello (1990-10-19). "Transgenic mice expressing a human poliovirus receptor: a new model for poliomyelitis". Cell. 63 (2): 353–362. doi:10.1016/0092-8674(90)90168-E. ISSN 0092-8674. PMID 2170026. S2CID 11946113.
  16. ^ Kauder, Steven E.; Vincent R. Racaniello (2004-06-15). "Poliovirus tropism and attenuation are determined after internal ribosome entry". Journal of Clinical Investigation. 113 (12): 1743–1753. doi:10.1172/JCI21323. ISSN 0021-9738. PMC 420511. PMID 15199409.
  17. ^ O'Neill, R. E.; V. R. Racaniello (December 1989). "Inhibition of translation in cells infected with a poliovirus 2Apro mutant correlates with phosphorylation of the alpha subunit of eucaryotic initiation factor 2". Journal of Virology. 63 (12): 5069–5075. doi:10.1128/JVI.63.12.5069-5075.1989. ISSN 0022-538X. PMC 251168. PMID 2555543.
  18. ^ Morrison, J. M.; V. R. Racaniello (2009-05-01). "Proteinase 2Apro Is Essential for Enterovirus Replication in Type I Interferon-Treated Cells". Journal of Virology. 83 (9): 4412–4422. doi:10.1128/JVI.02177-08. ISSN 0022-538X. PMC 2668472. PMID 19211759.
  19. ^ Kim, M. S.; V. R. Racaniello (2007-08-15). "Enterovirus 70 Receptor Utilization Is Controlled by Capsid Residues That Also Regulate Host Range and Cytopathogenicity". Journal of Virology. 81 (16): 8648–8655. doi:10.1128/JVI.01569-06. ISSN 0022-538X. PMC 1951352. PMID 17537857.
  20. ^ Harris, J. R.; V. R. Racaniello (2005-05-01). "Amino Acid Changes in Proteins 2B and 3A Mediate Rhinovirus Type 39 Growth in Mouse Cells". Journal of Virology. 79 (9): 5363–5373. doi:10.1128/JVI.79.9.5363-5373.2005. ISSN 0022-538X. PMC 1082767. PMID 15827151.
  21. ^ Harris, J. R.; V. R. Racaniello (2003-04-15). "Changes in Rhinovirus Protein 2C Allow Efficient Replication in Mouse Cells". Journal of Virology. 77 (8): 4773–4780. doi:10.1128/JVI.77.8.4773-4780.2003. ISSN 0022-538X. PMC 152148. PMID 12663784.
  22. ^ Drahos, J.; V. R. Racaniello (2009-11-15). "Cleavage of IPS-1 in Cells Infected with Human Rhinovirus". Journal of Virology. 83 (22): 11581–11587. doi:10.1128/JVI.01490-09. ISSN 0022-538X. PMC 2772720. PMID 19740998.
  23. ^ Hughes, Scott A.; Harshwardhan M. Thaker; Vincent R. Racaniello (2003-12-23). "Transgenic Mouse Model for Echovirus Myocarditis and Paralysis". Proceedings of the National Academy of Sciences of the United States of America. 100 (26): 15906–15911. Bibcode:2003PNAS..10015906H. doi:10.1073/pnas.2535934100. JSTOR 3149104. PMC 307666. PMID 14673080.
  24. ^ Racaniello, Vincent. "Research Interests of the Racaniello Lab". Columbia University. Retrieved 23 August 2014.
  25. ^ Rosenfeld, Amy B.; David J. Doobin; Audrey L. Warren; Vincent R. Racaniello; Richard B. Vallee (2017-11-14). "Replication of early and recent Zika virus isolates throughout mouse brain development". Proceedings of the National Academy of Sciences of the United States of America. 114 (46): 12273–12278. Bibcode:2017PNAS..11412273R. doi:10.1073/pnas.1714624114. PMC 5699088. PMID 29087938.
  26. ^ Rosenfeld, Amy B.; Audrey L. Warren; Vincent R. Racaniello (2019-10-22). "Neurotropism of enterovirus D68 isolates is independent of sialic acid and is not a recently acquired phenotype". mBio. 10 (5): e02370-19. doi:10.1128/mBio.02370-19. PMC 6805996. PMID 31641090.
  27. ^ Rosenfeld, Amy B.; Edmund Qian Long Shen; Michaela Melendez; Nischay Mishra; W.Ian Lipkin; Vincent R. Racaniello (2022-01-18). "Cross-Reactive Antibody Responses against Nonpoliovirus Enteroviruses". mBio. 13 (1): e03660-21. doi:10.1128/mbio.03660-21. PMC 8764532. PMID 5038922.
  28. ^ "BioCrowd". BioCrowd. Retrieved 22 August 2014.
  29. ^ Racaniello, Vincent. "Virology blog about viruses and viral disease". Vincent Racaniello. Retrieved 22 August 2014.
  30. ^ Racaniello, Vincent. "TWIV this week in virology". Vincent Racaniello. Retrieved 22 August 2014.
  31. ^ "This Week in Parasitism". Microbe World. American Society for Microbiology. Archived from the original on 16 August 2014. Retrieved 22 August 2014.
  32. ^ "Dr. Dickson Despommier". Columbia University. Retrieved 22 August 2014.
  33. ^ "This Week in Microbiology". Microbe World. American Society for Microbiology. Retrieved 22 August 2014.
  34. ^ "This Week in Evolution". Microbe World. American Society for Microbiology. Retrieved 22 August 2014.
  35. ^ "Nels Elde". University of Utah. Retrieved 22 August 2014.
  36. ^ "Immune". Microbe World. American Society for Microbiology. Retrieved 22 August 2014.
  37. ^ Racaniello, Vincent (23 June 2009). "Influenza 101". Vincent Racaniello. Retrieved 22 August 2014.
  38. ^ Racaniello, Vincent (12 August 2009). "Virology 101". Vincent Racaniello. Retrieved 22 August 2014.
  39. ^ Racaniello, Vincent. "Virology – Biology W3310/4310". V. Racaniello. Retrieved 22 August 2014.
  40. ^ Racaniello, Vincent. "Virology Live". YouTube.
  41. ^ Racaniello, Vincent. "Q&A with A&V Livestream". YouTube.
  42. ^ Racaniello, Vincent. "Office Hours with Earth's Virology Professor". YouTube.
  43. ^ Patents
    • Almond, Jeffrey W.; Michael a Skinner; Vincent Racaniello; Philip D. Minor (1994-02-15), Attenuated polioviruses, retrieved 2014-08-24
    • Almond, Jeffrey William; Road London; Michael Anthony Skinner; Hills Road Biology; Vincent Racaniello; Surgeons of Columbia University 701; Philip David Minor; Blanche Lane South Mimms Control (1993-08-15), Attenuierte Viren., retrieved 2014-08-24{{citation}}: CS1 maint: numeric names: authors list (link)
    • Jeffrey, William Almond; a Skinner Michael; Racaniello Vincent; David Minor Philip (1989-09-27), Attenuated Viruses, retrieved 2014-08-24
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