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. His laboratory identified CD155 (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. 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 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 (J Clin Invest, 2004: 113 1743-1753).
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 (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.
Read more about this topic: Vincent Racaniello
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