|
|
 |
|
|
Transcriptional attenuation of the type 1 interferon response by rhinovirus |
Co-P.I. Kurt Gustin
Abstract |
 |
| |
|
The dsRNA response is a critical defense pathway used by cells to defend against viral infection. Critical for the function of
this pathway is the production of IFN-beta, which requires the coordinated assembly of NF-kappaB, IRF-3 and ATF-2 on the
IFN-beta enhancer. NF-kappaB and IRF-3 are two transcription factors that are normally found in the cytoplasm, but upon
exposure to dsRNA translocate into the nucleus where they activate transcription of IFN-beta and other target genes. ATF-2 is
present constitutively in the nucleus and is phosphorylated and associates with c-jun in response to dsRNA exposure. Recently,
we found that infection of HeLa cells with rhinovirus type 14 (RV14) activates the cellular dsRNA response as evidenced by the
nuclear translocation of NF-kappaB and IRF-3 and phosphorylation of ATF-2. Despite this, no accumulation of IFN-beta mRNA is
observed, suggesting that rhinovirus has in place a mechanism that attenuates this response. The overall goals of this
proposal are to determine the underlying mechanisms responsible for inhibition of the dsRNA response by rhinovirus. The major
aim of this proposal is to utilize nuclear run-ons to determine if inhibition of IFN-beta mRNA accumulation is due to a block
in transcription initiation or to increased turnover in infected cells. If regulation is at the level of initiation,
experiments are proposed to examine the assembly and activation of transcription factors necessary for induction of IFN-beta
mRNA synthesis. This will include analyzing DNA binding of NF-kappaB, IRF-3 and ATF-2 on the IFN-beta enhancer. If we do not
observe an inhibition of transcription initiation this would suggest that RV14 induces the rapid turnover of IFN-beta mRNA.
This will be confirmed by measuring the half-life of IFN-beta mRNA in RV14-infected cells. In addition, we will identify the
sequences and trans-acting factors responsible for destabilizing the IFN-beta mRNA by mutagenesis and UV-crosslinking.
|
| |
|
|
|
| researchers |
| Gustavo Arrizabalaga |
 |
| Potassium sensing by the obligate intracellular parasite Toxoplasma gondii |
|
| More info... |
| |
| Lee Fortunato |
 |
| Human cytomegalovirus interactions with cellular p53 |
|
| More info... |
| |
| Mark McGuire |
 |
| The impact of lipid metabolism on staphylococcal mastitis |
|
| More info... |
| |
| Bruce Miller |
 |
| Maintenance of hyphal polarity and its role in Aspergillus pathogenesis |
|
| More info... |
| |
| Tanya Miura |
 |
| Regulation of the immune response to coronavirus infection in the lung |
|
| More info... |
| |
| pilot project researchers |
| Jill Johnson |
 |
| Role of Hsp90 in polarized cell morphogenesis in S. cerevisiae and C. albicans |
|
| More info... |
| |
| Carolyn Hovde Bohach |
 |
| The role of the large 'invasin-like' Y. pestis gene in pathogensis |
|
| More info... |
| |
| Scott Minnich |
 |
| The role of the large 'invasin-like' Y. pestis gene in pathogensis |
|
| More info... |
| |
|
