Abstract

Coronaviruses are enveloped RNA viruses that cause a variety of diseases in humans and animals. Coronavirus RNA transcription involves interactions between the leader RNA and the intergenic sequences (IGS) where subgenomic mRNA synthesis is initiated. It has been proposed that the leader-IGS interaction is mediated by direct RNA-RNA interactions between complementary sequences. Using a mutant of mouse hepatitis virus (MHV) called JHM2c, a subset of subgenomic mRNA species were found that resulted from initiation at various sites in the IGS where no sequence complementarity to the leader exists. This lead to the hypothesis that protein-RNA and protein-protein interactions, rather than RNA-RNA interactions are the driving force for the initiation of mRNA transcription. The heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is a potential cellular factor involved in the regulation of MHV RNA transcription and experiments to test the involvement of hnRNP-A1 in coronavirus transcription are proposed.
The first aim will define the interactions between hnRNP-A1 and the cis-acting sequences of MHV RNA both in vitro and in vivo, and then determine the functional significance of this protein-RNA interaction in the regulation of MHV RNA transcription.
The second aim will characterize the interactions between hnRNP-A1 and the MHV RNA polymerase and nucleocapsid proteins, and then determine the functional significance of these protein-protein interactions in the regulation of MHV RNA transcription.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI047188-03
Application #
6511237
Study Section
Virology Study Section (VR)
Program Officer
Beisel, Christopher E
Project Start
2000-03-15
Project End
2004-02-28
Budget Start
2002-03-01
Budget End
2003-02-28
Support Year
3
Fiscal Year
2002
Total Cost
$249,060
Indirect Cost

  Institution

Name
University of Arkansas for Medical Sciences
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
Little Rock
State
AR
Country
United States
Zip Code
72205

  Publications

Cai, Yingyun; Liu, Yin; Zhang, Xuming (2007) Suppression of coronavirus replication by inhibition of the MEK signaling pathway. J Virol 81:446-56
Liu, Yin; Zhang, Xuming (2006) Persistent coronavirus infection of progenitor oligodendrocytes. Adv Exp Med Biol 581:379-84
Cai, Yingyun; Liu, Yin; Zhang, Xuming (2006) Induction of transcription factor Egr-1 gene expression in astrocytoma cells by Murine coronavirus infection. Virology 355:152-63
Yu, Dongdong; Zhang, Xuming (2006) Differential induction of proinflammatory cytokines in primary mouse astrocytes and microglia by coronavirus infection. Adv Exp Med Biol 581:407-10
Liu, Yin; Zhang, Xuming (2005) Expression of cellular oncogene Bcl-xL prevents coronavirus-induced cell death and converts acute infection to persistent infection in progenitor rat oligodendrocytes. J Virol 79:47-56
Liu, Yin; Cai, Yingyun; Zhang, Xuming (2003) Induction of caspase-dependent apoptosis in cultured rat oligodendrocytes by murine coronavirus is mediated during cell entry and does not require virus replication. J Virol 77:11952-63
Cai, Yingyun; Liu, Yin; Yu, Dongdong et al. (2003) Down-regulation of transcription of the proapoptotic gene BNip3 in cultured astrocytes by murine coronavirus infection. Virology 316:104-15
Popova, Rada; Zhang, Xuming (2002) The spike but not the hemagglutinin/esterase protein of bovine coronavirus is necessary and sufficient for viral infection. Virology 294:222-36
Zhang, X (2001) Heterogeneity of subgenomic mRNAs of a mutant mouse hepatitis virus strain JHM2C. Adv Exp Med Biol 494:541-6
Zhang, X (2001) Identification of a noncanonical transcription initiation site for transcription of a subgenomic mRNA of mouse hepatitis virus. Adv Exp Med Biol 494:563-70

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