This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Silvestri, L. S.
Right arrow Articles by Patton, J. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Silvestri, L. S.
Right arrow Articles by Patton, J. T.

 Previous Article  |  Next Article 

Journal of Virology, December 2005, p. 15165-15174, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15165-15174.2005

Rotavirus Glycoprotein NSP4 Is a Modulator of Viral Transcription in the Infected Cell

Lynn S. Silvestri,{dagger} M. Alejandra Tortorici,{ddagger} Rodrigo Vasquez-Del Carpio, and John T. Patton*

Laboratory of Infectious Diseases, NIAID, National Institutes of Health, Bethesda, Maryland 20892

Received 5 August 2005/ Accepted 21 September 2005

The outer shell of the rotavirus triple-layered virion is lost during cell entry, yielding a double-layered particle (DLP) that directs synthesis of viral plus-strand RNAs. The plus-strand RNAs act as templates for synthesis of the segmented double-stranded RNA (dsRNA) genome in viral inclusion bodies (viroplasms). The viral endoplasmic reticulum (ER)-resident glycoprotein NSP4 recruits progeny DLPs formed in viroplasms to the ER, where the particles are converted to triple-layered particles (TLPs) via budding. In this study, we have used short interfering RNAs to probe the role of NSP4 in the viral life cycle. Our analysis showed that knockdown of NSP4 expression had no marked effect on the expression of other viral proteins or on the replication of the dsRNA genome segments. However, NSP4 loss of function suppressed viroplasm maturation and caused a maldistribution of nonstructural and structural proteins that normally accumulate in viroplasms. NSP4 loss of function also inhibited formation of packaged virus particles, instead inducing the accumulation of empty particles. Most significant was the observation that NSP4 knockdown led to dramatically increased levels of viral transcription late in the infection cycle. These findings point to a multifaceted role for NSP4 in virus replication, including influencing the development of viroplasms, linking genome packaging with particle assembly, and acting as a modulator of viral transcription. By recruiting transcriptionally active or potentially active DLPs to the ER for conversion to quiescent TLPs, NSP4 acts as a feedback inhibitor down-regulating viral transcription when adequate levels of plus-strand RNAs are available to allow for productive infection.

* Corresponding author. Mailing address: Laboratory of Infectious Diseases, NIAID, National Institutes of Health, 50 South Dr., MSC 8026, Room 6314, Bethesda, MD 20892-8026. Phone: (301) 594-1615. Fax: (301) 496-8312. E-mail: jpatton{at}niaid.nih.gov.

{dagger} Present address: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702.

{ddagger} Present address: Virologie Moléculaire et Structurale, Unité Mixte de Recherche, CNRS-INRA, 91198 Gif-sur-Yvette, France.

Journal of Virology, December 2005, p. 15165-15174, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15165-15174.2005




This article has been cited by other articles:

  • Ayala-Breton, C., Arias, M., Espinosa, R., Romero, P., Arias, C. F., Lopez, S. (2009). Analysis of the Kinetics of Transcription and Replication of the Rotavirus Genome by RNA Interference. J. Virol. 83: 8819-8831 [Abstract] [Full Text]  
  • Zambrano, J. L., Diaz, Y., Pena, F., Vizzi, E., Ruiz, M.-C., Michelangeli, F., Liprandi, F., Ludert, J. E. (2008). Silencing of Rotavirus NSP4 or VP7 Expression Reduces Alterations in Ca2+ Homeostasis Induced by Infection of Cultured Cells. J. Virol. 82: 5815-5824 [Abstract] [Full Text]  
  • Rajasekaran, D., Sastri, N. P., Marathahalli, J. R., Indi, S. S., Pamidimukkala, K., Suguna, K., Rao, C. D. (2008). The flexible C terminus of the rotavirus non-structural protein NSP4 is an important determinant of its biological properties. J. Gen. Virol. 89: 1485-1496 [Abstract] [Full Text]  
  • Campagna, M., Budini, M., Arnoldi, F., Desselberger, U., Allende, J. E., Burrone, O. R. (2007). Impaired hyperphosphorylation of rotavirus NSP5 in cells depleted of casein kinase 1{alpha} is associated with the formation of viroplasms with altered morphology and a moderate decrease in virus replication. J. Gen. Virol. 88: 2800-2810 [Abstract] [Full Text]  
  • Bugarcic, A., Taylor, J. A. (2006). Rotavirus Nonstructural Glycoprotein NSP4 Is Secreted from the Apical Surfaces of Polarized Epithelial Cells. J. Virol. 80: 12343-12349 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»