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Published on: January 24, 2016
Inhibition of STAT 1 phosphorylation by human parainfluenza virus type 3 C protein
Achut G Malur1, Santanu Chattopadhyay, Ratan K Maitra
1Cleveland Clinic Foundation, Section Virology NN-10, Department of Molecular Biology, 9500 Euclid Avenue, Cleveland, OH 44195-5178, USA.
Abstract:
The P mRNA of the viruses belonging to the subfamily Paramyxovirinae possesses a unique property of giving rise to several accessory proteins by a process that involves the utilization of overlapping open reading frames (the C proteins) and by an "RNA-editing" mechanism (the V proteins). Although these proteins are considered accessory, numerous studies have highlighted the importance of these proteins in virus transcription and interferon signaling, including our previous observation on the role of human parainfluenza virus type 3 (HPIV 3) C protein in the transcription of viral genome (Malur et al., Virus Res. 99:199-204, 2004). In this report, we have addressed its role in interferon signaling by generating a stable cell line, L-C6, by using the lentiviral expression system which expresses HPIV 3 C protein. The L-C6 cells were efficient in abrogating both alpha and gamma interferon-induced antiviral states and demonstrated a drastic reduction in the formation of gamma-activated factor complexes in the cell extracts. Western blot analysis subsequently revealed a defect in the phosphorylation of STAT 1 in these cells. Taken together, our results indicate that HPIV 3 C protein is capable of counteracting the interferon signaling pathway by specifically inhibiting the activation of STAT 1.
Insights
The human parainfluenza virus type 3 C protein inhibits the interferon signaling pathway. This accessory protein prevents STAT 1 activation, crucial for antiviral responses.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Paramyxovirinae subfamily viruses produce accessory proteins (C and V proteins) from P mRNA.
- The human parainfluenza virus type 3 (HPIV 3) C protein is known to play a role in viral transcription.
- Accessory proteins are increasingly recognized for their importance in virus transcription and interferon signaling.
Purpose of the Study:
- To investigate the role of the HPIV 3 C protein in interferon signaling.
- To generate a stable cell line expressing HPIV 3 C protein for experimental analysis.
Main Methods:
- Generation of a stable lentiviral expression cell line (L-C6) for HPIV 3 C protein.
- Assessment of interferon-induced antiviral states in L-C6 cells.
- Analysis of gamma-activated factor complex formation and STAT 1 phosphorylation via Western blot.
Main Results:
- L-C6 cells showed abrogated alpha and gamma interferon-induced antiviral states.
- A significant reduction in gamma-activated factor complex formation was observed.
- Western blot analysis revealed a defect in STAT 1 phosphorylation in L-C6 cells.
Conclusions:
- HPIV 3 C protein effectively counteracts the interferon signaling pathway.
- The C protein specifically inhibits STAT 1 activation, a key component of interferon signaling.
- This study elucidates a novel mechanism by which HPIV 3 evades host antiviral defenses.
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