Nuclear Localization of Flavivirus RNA Synthesis in Infected Cells

Uchil, Pradeep Devappa and Kumar, Anil VA and Satchidanandam, Vijaya (2006) Nuclear Localization of Flavivirus RNA Synthesis in Infected Cells. In: Journal Of Virology, 80 (11). pp. 5451-5464.

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Abstract

Flaviviral replication is believed to be exclusively cytoplasmic, occurring within virus-induced membrane-bound replication complexes in the host cytoplasm. Here we show that a significant proportion (20%) of the total RNA-dependent RNA polymerase (RdRp) activity from cells infected with West Nile virus, Japanese encephalitis virus (JEV), and dengue virus is resident within the nucleus. Consistent with this, the major repticase proteins NS3 and NS5 of JEV also localized within the nucleus. NS5 was found distributed throughout the nucleoplasm, but NS3 was present at sites of active flaviviral RNA synthesis, colocalizing with NS5, and visible as distinct foci along the inner periphery of the nucleus by confocal and immunoelectron microscopy. Both these viral repticase proteins were also present in the nuclear matrix, colocalizing with the peripheral lamina, and revealed a well-entrenched nuclear location for the viral replication complex. In keeping with this observation, antibodies to either NS3 or NS5 coimmunoprecipitated the other protein from isolated nuclei along with newly synthesized viral RNA. Taken together these data suggest an absolute requirement for both of the replicase proteins for nucleus-localized synthesis of flavivirus RNA. Thus, we conclusively demonstrate for the first time that the host cell nucleus functions as an additional site for the presence of functionally active flaviviral replicase complex.

Item Type:	Journal Article
Publication:	Journal Of Virology
Publisher:	American Society For Microbiology
Additional Information:	Copyright of his article belongs to American Society For Microbiology.
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	02 Apr 2009 06:29
Last Modified:	19 Sep 2010 04:59
URI:	http://eprints.iisc.ac.in/id/eprint/17986

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