Vincent Racaniello
Encyclopedia
Vincent R. Racaniello is a Higgins Professor in the Department of Microbiology and Immunology at Columbia University
Columbia University
Columbia University in the City of New York is a private, Ivy League university in Manhattan, New York City. Columbia is the oldest institution of higher learning in the state of New York, the fifth oldest in the United States, and one of the country's nine Colonial Colleges founded before the...

’s College of Physicians and Surgeons. He is one of four virologists who has recently authored Principles of Animal Virology, a respected textbook
used by many teaching virology to undergraduate, medical and post-graduate students. As
an esteemed member of the scientific community, Racaniello has received several
awards including Irma T. Hirschl, Searle Scholars, Eli Lilly and NIH Merit. He has also
been a Harvey Society Lecturer at Rockefeller University
Rockefeller University
The Rockefeller University is a private university offering postgraduate and postdoctoral education. It has a strong concentration in the biological sciences. It is also known for producing numerous Nobel laureates...

, the Hilleman Lecturer at the
University of Chicago, and University Lecturer at Columbia University. Racaniello has served on the editorial boards of scientific journals, including the Journal of Virology, and is a community editor for the open access journal PLOS Pathogens.

Education

Racaniello graduated from Cornell University
Cornell University
Cornell University is an Ivy League university located in Ithaca, New York, United States. It is a private land-grant university, receiving annual funding from the State of New York for certain educational missions...

 in 1974 (BA, biological sciences) and completed his PhD in the laboratory of Peter Palese
Peter Palese
Peter Palese, Ph.D, is an American microbiologist and Professor and Chair of the Department of Microbiology at the Mount Sinai Medical Center in New York City, and an expert in the field of RNA viruses....

 in 1980, studying genetic reassortment of influenza virus. As a post-doctoral fellow in David Baltimore
David Baltimore
David Baltimore is an American biologist, university administrator, and Nobel laureate in Physiology or Medicine. He served as president of the California Institute of Technology from 1997 to 2006, and is currently the Robert A. Millikan Professor of Biology at Caltech...

's laboratory at MIT (1979–1982), Racaniello used recombinant DNA
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...

 technology to clone and sequence the genome of the small RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

 animal virus poliovirus
Poliovirus
Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and member of the family of Picornaviridae.Poliovirus is composed of an RNA genome and a protein capsid. The genome is a single-stranded positive-sense RNA genome that is about 7500 nucleotides long. The viral particle is...

. Using these tools he generated the first infectious clone of an animal RNA virus (Science, 1981: 214 916-919). Construction of the infectious clone revolutionized modern virology
Virology
Virology is the study of viruses and virus-like agents: their structure, classification and evolution, their ways to infect and exploit cells for virus reproduction, the diseases they cause, the techniques to isolate and culture them, and their use in research and therapy...

.

Research

Racaniello established his own research laboratory at Columbia University in the fall of
1982. The aim of his laboratory is to understand replication and pathogenesis of small
RNA animal viruses Picornaviruses. The life cycle of a virus begins with its attachment
to and entry into the cytoplasm of a cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

. His laboratory identified CD155
CD155
CD155 also known as the poliovirus receptor is a protein that in humans is encoded by the PVR gene.- Function :CD155 is a Type I transmembrane glycoprotein in the immunoglobulin superfamily...

 (poliovirus
receptor, PVR); a cell surface protein, and member of the immunoglobin superfamily as
the protein that mediates this process (PNAS, 1986: 83 7845-7849; Cell, 1989: 56
855-865). Understanding how the interaction between virus and cell alters the viral
particle and how virus entry is facilitated by the interaction has helped elucidate the
means by which poliovirus infection is initiated (JBC, 2000: 275 23809-23096; JV, 2001:
75 4984-4989) .

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
Poliomyelitis
Poliomyelitis, often called polio or infantile paralysis, is an acute viral infectious disease spread from person to person, primarily via the fecal-oral route...

. Mice
producing the human CD155 protein were generated and infected with poliovirus (Cell,
1990: 63 353-62). These mice exhibited all symptoms and pathology of
poliomyelitis observed in humans including flaccid paralysis and spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...

 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
Polio vaccine
Two polio vaccines are used throughout the world to combat poliomyelitis . The first was developed by Jonas Salk and first tested in 1952. Announced to the world by Salk on April 12, 1955, it consists of an injected dose of inactivated poliovirus. An oral vaccine was developed by Albert Sabin...

.

Poliomyelitis is a disease of the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

; 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
Hepatitis C virus
Hepatitis C virus is a small , enveloped, positive-sense single-stranded RNA virus of the family Flaviviridae...

,
a liver specific virus, or coxsackievirus
Coxsackievirus
Coxsackievirus is a virus that belongs to a family of non enveloped linear positive-sense ssRNA viruses, Picornaviridae and the genus Enterovirus, which also includes poliovirus and echovirus. Enteroviruses are among the most common and important human pathogens and ordinarily its members are...

 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 (J Clin Invest,
2004: 113 1743-1753).

Secretion of interferon
Interferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...

 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 (JV, 1989: 63 5069-5075; JV, 2009: 83 4412-4422).
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

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 life cycle and pathogenesis of other picornaviruses similar to poliovirus.
These viruses include enterovirus
Enterovirus
Enteroviruses are a genus of ssRNA viruses associated with several human and mammalian diseases. Serologic studies have distinguished 66 human enterovirus serotypes on the basis of antibody neutralization tests. Additional antigenic variants have been defined within several of the serotypes on the...

 70 (EV70), human rhinovirus
Rhinovirus
Human rhinoviruses are the most common viral infective agents in humans and are the predominant cause of the common cold. Rhinovirus infection proliferates in temperatures between 33–35 °C , and this may be why it occurs primarily in the nose...

,
coxsackievirus
Coxsackievirus
Coxsackievirus is a virus that belongs to a family of non enveloped linear positive-sense ssRNA viruses, Picornaviridae and the genus Enterovirus, which also includes poliovirus and echovirus. Enteroviruses are among the most common and important human pathogens and ordinarily its members are...

 A21 and echovirus 1. Infectious clones of EV70 and several serotypes of
rhinoviruses were generated (JV, 2007: 81 8648-8655; JV, 2005: 79 5363-5373; JV, 2003:
77 4773-4780). 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
Interferon type I
Human type I interferons comprise a vast and growing group of IFN proteins.All type I IFNs bind to a specific cell surface receptor complex known as the IFN-α receptor that consists of IFNAR1 and IFNAR2 chains....

 response. Infection of cultured cells with human rhinovirus 1A results in the cleavage of the integral component IPS-1 (MAVS, Cardif) (JV, 2009: 83 11581-11587).
In addition a small animal model of virus echovirus 1 pathogenesis has been established
(PNAS, 2003: 100 15906-15011).

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.

Science beyond the laboratory

Understanding that the World Wide Web is a primary scientific tool, Racaniello is one of the co-creators of BioCrowd, a social network designed to bring together scientists of all disciplines. Racaniello's blog virology, virology 'twitter-like' site and net-casts 'This week in virology' and 'This week in parasitism' with colleague Dickson Despommier
Dickson Despommier
Dickson D. Despommier is a microbiologist, ecologist and Professor of Public Health in Environmental Health Sciences at Columbia University. He conducts research on intracellular parasitism and teaches courses on Parasitic Diseases, Medical Ecology and Ecology. In recent years, Despommier has...

and 'This week in Microbiology" with Cliff Mintz, Michael Schmidt and Stanley Maloy also unifies science with technology. Unlike BioCrowd however, his blog, net-casts, virus encyclopedia and specialized blogs 'influenza 101' and 'virology 101' are to bring microbiology to those outside of the field. Continuing to bring virology to those outside of the field, Racaniello has established a library containing podcasts of lectures he has recently given at Columbia University.
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