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J. Virol. doi:10.1128/JVI.01859-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The Transdominant Endogenous Retrovirus enJS56A1 Associates with and Blocks Intracellular Trafficking of the JSRV Gag

Institute of Comparative Medicine, University of Glasgow Veterinary School, Glasgow, Scotland

^* To whom correspondence should be addressed. Email: m.palmarini{at}vet.gla.ac.uk.

	Abstract

The sheep genome harbors approximately 20 endogenous retroviruses (enJSRVs) highly related to the exogenous Jaagsiekte sheep retrovirus (JSRV). One of the enJSRV loci, enJS56A1, acts as a unique restriction factor by blocking JSRV in a transdominant fashion at a late stage of the retroviral cycle. To better understand the molecular basis of this restriction (termed JLR for JSRV late restriction), we functionally characterized JSRV and enJS56A1 Gag proteins. We identified the putative JSRV membrane binding and late domains, and determined their lack of involvement JLR. In addition, by using enJS56A1 truncation mutants we established that the entire Gag is necessary to restrict JSRV exit. By using differentially tagged viruses, we observed by confocal microscopy colocalization between JSRV and enJS56A1 Gag proteins. By co-immunoprecipitation and molecular complementation analysis we also revealed intracellular association and likely coassembly between JSRV and enJS56A1 Gag. Interestingly, JSRV and enJS56A1 Gag showed a distinct intracellular targeting: JSRV exhibited pericentrosomal accumulation of Gag staining while enJS56A1 did not accumulate in this region. Furthermore, the number of cells displaying pericentrosomal JSRV Gag is drastically reduced in the presence of enJS56A1. We identified amino acid residue R21 in JSRV Gag as the primary determinant of centrosome targeting. We conclude that JLR is dependent on Gag-Gag interaction between enJS56A1 and JSRV leading to altered cellular localization of the latter.

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