Interplay between miR27a and PPARγ-DUSP1 regulates BPXV mRNA translation via modulating p38α MAPK-MNK1-eIF4E signaling pathway.

Authors

Garvit Kumar, Assim Verma, Shweta Dhanda, Himanshu Kamboj, Riyesh Thachamvally, Shoor Vir Singh, Ram Kumar, Naveen Kumar

Published in

Virus research. Pages 199811. Sep 29, 2026. Epub Sep 29, 2026.

Abstract

In this study, we demonstrate that activation of PPARγ (Peroxisome Proliferator-Activated Receptor Gamma), a nuclear receptor and transcription factor, by its agonist Rosiglitazone significantly suppresses replication of Buffalopox virus (BPXV). Time-of-addition and step-specific assays revealed that rosiglitazone primarily inhibits viral genome replication and protein synthesis, while showing no measurable effect on viral attachment, entry, or release in infected cells. Mechanistic investigations identified miR-27a, an endogenous negative regulator of PPARγ, as a proviral factor displaying an inverse expression pattern with PPARγ during infection. At 12 hours post-infection, corresponding to the peak of viral mRNA translation, miR-27a expression was maximal whereas PPARγ levels were markedly reduced, suggesting a critical regulatory axis controlling viral translation. Activation of PPARγ suppressed the p38α MAPK-MNK1-eIF4E signaling pathway required for cap-dependent viral mRNA translation. Notably, the antiviral effect of rosiglitazone was abolished in p38α-knockout cells, confirming the involvement of p38α signaling. Although PPARγ did not directly interact with p38α, it induced the expression of DUSP1, a known negative regulator of p38α activity. Pharmacological inhibition of DUSP1 restored viral replication in rosiglitazone-treated cells, supporting a PPARγ-DUSP1-mediated mechanism. Furthermore, rosiglitazone significantly reduced BPXV-induced mortality and pock lesion formation on the chorioallantoic membrane of specific pathogen-free embryonated chicken eggs. Importantly, prolonged viral passage in the presence of the inhibitor did not lead to the emergence of resistant variants, underscoring the potential of rosiglitazone as a host-directed antiviral strategy with a low likelihood of inducing antiviral resistance.

PMID:
42810689
Bibliographic data and abstract were imported from PubMed on 30 Sep 2026.

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