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Journal of Virology, February 2001, p. 1476-1486, Vol. 75, No. 3
Laboratory of Molecular Neurovirology, Center
for Neurovirology and Cancer Biology, College of Science and
Technology, Temple University, Philadelphia, Pennsylvania
19122,1 Laboratory of Molecular & Cellular Pathology, School of Medicine,2 and
Laboratory of Comparative Pathology, Graduate School of
Veterinary Medicine,3 Hokkaido
University, and CREST, Japan Science and Technology
Corporation,4 Sapporo, Japan
Received 27 July 2000/Accepted 26 October 2000
In addition to encoding the structural and regulatory proteins,
many viruses encode auxiliary proteins, some of which have been shown
to play important roles in lytic and latent states of the viruses. The
human neurotropic JC virus (JCV) genome encodes an auxiliary protein
called Agno whose function remains unknown. Here, we investigated the
functional role of JCV Agno protein on transcription and replication of
the viral genome in glial cells. Results from transfection of human
glial cells showed that Agno protein suppresses both T-antigen-mediated
transcription of the viral late gene promoter and T-antigen-induced
replication of viral DNA. Affinity chromatography and
coimmunoprecipitation assays demonstrated that the Agno protein and T
antigen physically interact with each other. Through the use of a
series of deletion mutants, we demonstrated that the
T-antigen-interacting region of Agno protein is localized to its
amino-terminal half and the Agno-interacting domain of T antigen maps
to its central portion. Furthermore, utilizing various Agno deletion
mutants in functional studies, we confirmed the importance of the
Agno-T antigen interaction in the observed down-modulation of T antigen
function upon viral gene transcription and DNA replication by Agno
protein. Taken together these data suggest that the Agno protein of
JCV, which is produced late during the late phase of the lytic cycle,
can physically and functionally interact with the viral early protein, T antigen, and downregulate viral gene expression and DNA replication. The importance of these observations in the lytic cycle of JCV is discussed.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.3.1476-1486.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Interaction of JC Virus Agno Protein with T Antigen
Modulates Transcription and Replication of the Viral Genome in
Glial Cells
*
Corresponding author. Mailing address: Laboratory of
Molecular Neurovirology, Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, 1900 N. 12th St.,
015-96, Room 203, Philadelphia, PA 19122. Phone: (215) 204-0678. Fax:
(215) 204-0679. E-mail: kkhalili{at}astro.temple.edu.
Journal of Virology, February 2001, p. 1476-1486, Vol. 75, No. 3
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.3.1476-1486.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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