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Bovine herpesvirus 1 (BoHV-1) productive infection induces the generation of DNA double-strand breaks (DSBs), which may consequently lead to cell apoptosis. In response to DSBs, the DNA damage repair-related protein 53BP1 is recruited to the sites of DSBs, leading to the formation of 53BP1foci, which are crucial for the repair of damaged DNA and maintaining genomic integrity by repairing DSBs. In this study, we discovered that HMGA1 may play a significant role in counteracting virus infection-induced DNA damage, as the siRNA-mediated knockdown of HMGA1 protein expression or inhibition of HMGA1 activity by the chemical inhibitor Netropsin uniformly exacerbates the DNA damage induced by BoHV-1 productive infection. Interestingly, HMGA1 may positively regulate 53BP1 expression, and treatment with Netropsin reduced the accumulation of 53BP1 protein in the nucleus, suggesting that HMGA1 may potentially influence 53BP1's nuclear localization. However, this effect was reversed in the context of virus infection. Furthermore, Netropsin treatment restored the disruption of 53BP1 foci caused by virus infection, which is consistent with our findings that Netropsin enhances the nuclear accumulation of 53BP1. Collectively, these results indicate that HMGA1 is involved in countering DNA damage induced by virus infection. HMGA1 does indeed modulate the nuclear accumulation of 53BP1 protein, but this effect is counteracted by virus infection. Therefore, the biological function of HMGA1 in countering virus infection-induced DNA damage may be independent of its regulation of 53BP1 signaling. This is the first report suggesting that HMGA1 may be implicated in virus infection-induced DNA damage, although the precise mechanism remains to be elucidated. Furthermore, we report for the first time an interaction between HMGA1 and 53BP1, which is disrupted following virus infection. [ABSTRACT FROM AUTHOR]

Abstract Many viruses have been known to control key cellular signaling pathways to facilitate the virus infection. The possible involvement of signaling pathways in bovine herpesvirus type 1 (BoHV-1) infection is unknown. This study indicated that infection of MDBK cells with BoHV-1 induced an early-stage transient and a late-stage sustained activation of both phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen activated protein kinases/extracellular signal-regulated kinase 1/2 (MAPK/Erk1/2) signaling pathways. Analysis with the stimulation of UV-irradiated virus indicated that the virus binding and/or entry process was enough to trigger the early phase activations, while the late phase activations were viral protein expression dependent. Biphasic activation of both pathways was suppressed by the selective inhibitor, Ly294002 for PI3K and U0126 for MAPK kinase (MEK1/2), respectively. Furthermore, treatment of MDBK cells with Ly294002 caused a 1.5-log reduction in virus titer, while U0126 had little effect on the virus production. In addition, the inhibition effect of Ly294002 mainly occurred at the post-entry stage of the virus replication cycle. This revealed for the first time that BoHV-1 actively induced both PI3K/Akt and MAPK/Erk1/2 signaling pathways, and the activation of PI3K was important for fully efficient replication, especially for the post-entry stage.

Bovine herpesvirus 1(BoHV-1) is an important bovine pathogen that causes great economic loss to cattle farms worldwide. The virus-productive infection in bovine kidney (MDBK) cells results in ATP depletion. The mechanisms are not well understood. Mitochondrial fatty acid β-oxidation (FAO) is an important energy source in many tissues with high energy demand. Since carnitine palmitoyl-transferase 1 A (CPT1A) is the rate-limiting enzyme of FAO, we investigated the interactions between virus-productive infection and CPT1A signaling. Here, we found that virus-productive infection at the later stage significantly decreased CPT1A protein levels in all the detected cells, including MDBK, A549, and Neuro-2A cells, differentially altered the accumulation of CPT1A proteins in the nucleus and cytosol, and re-localized the protein in the nucleus. Etomoxir (ETO), an irreversible inhibitor of CPT1A, inhibited viral replication and partially interfered with the ability of BoHV-1 to alter CPT1A accumulation in the nucleus but not in the cytosol. Furthermore, ETO consistently reduced RNA levels of two viral regulatory proteins (bICP0 and bICP22) and protein expression of virion-associated proteins during productive infection, further supporting the important roles of CPT1A signaling in BoHV-1 productive infection. These data, for the first time, suggest that CPT1A is potentially involved in BoHV-1 productive infection. • BoHV-1 productive infection has effects on CPT1A protein expression and subcellular localization. • CPT1A signaling plays an important role in BoHV-1 productive infection. • BoHV-1 infection-induced nuclear accumulation of CPT1A was iterupted by CPT1A-specific inhibitor Etomoxir. [ABSTRACT FROM AUTHOR]

Phragmitesaustralis (P. australis), a worldwide distributed wetland grass, is traditionally used as food-making helper and spice in China. The pharmacological effect of this plant is poorly understood. Here, we demonstrated that lipopolysaccharide (LPS)-induced production of inflammatory mediators nitric oxide (NO) and reactive oxygen species (ROS), and the pro-inflammatory cytokines tumor necrosis factor-a (TNF-a) and interleukin-1β (IL-1β) in RAW264.7 macrophage were significantly inhibited by the crude extract. The inflammation pertinent signaling extra cellular signal-regulated kinase 1/2 (Erk1/2), P38MAPK, C-Jun and NF-kappaB (NF-κB) activated by LPS could be dramatically inhibited by this extract. It also remarkably inhibited bovine herpes virus type 1 (BoHV-1) replication in MDBK cells. Taken together, here, for the first time we provided P. australisa a novel natural herb as a potential candidate for the generation of antiviral and anti-inflammatory agent.