Unveiling the Antiviral Potential of chicken Poly (ADP-ribose) polymerases Against Influenza A Virus
Creators: name: Bandi, Jyothsna
Publisher: name: Lancaster University
Year: 2025

description: The Influenza A Virus (IAV) continues to pose a significant global health
 risk due to its capacity to trigger seasonal epidemics and occasional
 pandemics. Although vaccines and antiviral medications are available, the
 emergence of drug-resistant strains necessitates the development of novel
 therapeutic approaches. Poly (ADP-ribose) polymerases (PARPs) are a family
 of enzymes that participate in diverse cellular processes, such as DNA
 repair and immune response. Recent research has emphasized the potential
 of targeting PARPs as a novel antiviral strategy. This study aims to
 investigate the antiviral properties of the chicken PARP (chPARP) against
 IAV infection.
 
 
 To identify potential antiviral PARP candidates, we employed a
 bioinformatic approach to analyse the PARP family in chickens, which is a
 susceptible host for IAV infection. We focused on chPARP due to its unique
 structural features and potential role in antiviral immunity. To further
 investigate the antiviral mechanism of chPARP, we performed transcriptomic
 analysis to identify differentially expressed genes in IAV-infected cells
 treated with chPARPs. Our findings provides a comprehensive understanding
 of the role of PARP proteins in IAV infection. Bioinformatic analysis of
 chicken PARP genes revealed diverse domain organizations, evolutionary
 divergence, and potential antiviral roles. 
 
 RNA-seq analysis of IAV-infected cells identified over 3,700
 differentially expressed genes, including significant upregulation of
 several PARP family members, particularly PARP14. Functional studies on
 chPARP14 demonstrated its antiviral activity, with some truncated forms
 exhibiting reduced viral replication. Notably, full-length chPARP14 and
 chPARP14ΔCWC exhibited the most significant antiviral effects. While human
 PARP14 homologues showed varying antiviral activity, with some even
 exhibiting proviral effects, certain constructs, such as huPARP14ΔMACD,
 displayed potent antiviral activity. These findings highlight the
 potential of targeting PARPs, particularly chPARP14, for developing novel
 antiviral strategies. However, further research with increased sample
 sizes and 
 
 employing alternative approaches, such as chemical inhibition, RNA
 interference, and gene editing, is crucial to fully elucidate the role of
 PARPs in antiviral defence. This work has significant implications for our
 understanding of viral pathogenesis and the development of novel antiviral
 strategies. The identification of chPARP14 as a key player in antiviral
 defence, coupled with the observation that specific domains within the
 protein contribute to its antiviral activity, suggests novel therapeutic
 targets for combating IAV and potentially other viral infections.
 Furthermore, the study highlights the importance of considering
 species-specific variations in antiviral responses, as observed 
 
 in the differing antiviral activities of chicken and human PARP14
 homologues. These findings lay the groundwork for future investigations
 into the specific mechanisms of PARP14-mediated antiviral activity and the
 development of strategies to modulate its activity for therapeutic
 purposes.