bims-mevinf Biomed News
on Metabolism in viral infections
Issue of 2025–08–10
four papers selected by
Alexander Ivanov, Engelhardt Institute of Molecular Biology



  1. Front Cell Infect Microbiol. 2025 ;15 1643636
       Background & aims: Hepatitis B virus (HBV) infection remains a global health challenge. Tryptophan metabolism influences immune regulation, but its interplay with cytokines during antiviral therapy is unclear. We investigated associations between tryptophan pathways and cytokine profiles in the chronic hepatitis B (CHB) patients with varying treatment outcomes.
    Methods: This retrospective study included 106 CHB patients (including 29 functional cure cases) receiving nucleos(t)ide analogues (NAs) and 29 healthy controls. Plasma levels of 20 tryptophan metabolites (kynurenine, serotonin, and bacterial pathways) were quantified by HPLC-MS/MS, and 12 cytokines were measured via flow cytometry. Multivariate analyses were performed.
    Results: Functional cure patients showed unique metabolic patterns. Indole-3-carboxaldehyde (IAld) levels increased progressively from HBsAg positive groups (HBeAg-: 63.324 nmol/L; HBeAg+: 65.938 nmol/L) to functional cure (91.44 nmol/L) and healthy controls (130.634 nmol/L) (P < 0.01), exhibiting negative correlations with HBsAg (r = -0.31) and IFN-γ (r = -0.53) but positive correlation with IL-1β (r = 0.47). Picolinic acid (PA) was significantly elevated in the functional cure group (P < 0.001), associated with reduced HBsAg, IL-2 and increased IL-1β, IL-10 levels, indicating potential antiviral effects. Serotonin (5-HT) levels were higher in cured patients and correlated with IL-1β and IFN-α (P < 0.05). HBeAg-positive patients displayed increased kynurenine-to-tryptophan (Kyn/Trp) ratios (P < 0.05), while non-cured patients showed metabolic blockade downstream of 3-hydroxykynurenine (elevated 3-HK/Kyn ratios and reduced KA, XA/3-HK, 3-HAA/3-HK, and NAA levels; P < 0.05).
    Conclusions: The tryptophan metabolites (IAld, PA, 5-HT) were found to correlate with cytokine levels (IL-1β, IL-10), potentially implicating their involvement in immune regulation and antiviral responses. These observations delineate a metabolic-immune framework that may inform future therapeutic development for HBV.
    Keywords:  5-hydroxytryptamine; bacterial degradation pathway; chronic hepatitis B; cytokine profiles; functional cure; indole-3-carboxaldehyde; picolinic acid; tryptophan metabolism
    DOI:  https://doi.org/10.3389/fcimb.2025.1643636
  2. Free Radic Biol Med. 2025 Aug 05. pii: S0891-5849(25)00852-4. [Epub ahead of print]239 386-405
      Porcine epidemic diarrhea virus (PEDV) is a type of coronavirus that infects pigs, resulting in high mortality rates in piglets and posing a significant threat to the swine industry. However, the biological mechanisms underlying PEDV-induced intestinal damage and the role of oxidative stress in this context remain poorly understood. In the present study, quantitative proteomics was employed to identify key genes associated with PEDV infection. We established an in vivo PEDV infection model using piglets and conducted in vitro studies employing Z-nucleic acid (NA)-binding protein 1 (ZBP1) knockdown and knockout (KO) models in Vero E6 cells. Several techniques were used, including transmission electron microscopy, H&E staining, confocal laser scanning microscopy, TUNEL staining, and AO/EB staining, to assess morphological changes in the intestinal tissue of piglets and to evaluate alterations in oxidative stress, mitochondrial membrane potential, and PANoptosis-related marker molecules in cells. Our findings indicated that PEDV infection results in increased expression of ZBP1 and PANoptosis-related markers. In vitro experiments demonstrated that PEDV-N colocalizes with Z-RNA and ZBP1, and that oxidative stress inhibitors effectively mitigate PEDV-induced PANoptosis. Collectively, our results suggest that ZBP1 triggers cellular oxidative damage by recognizing Z-NA structures during PEDV invasion, thereby inducing apoptosis, pyroptosis, and necroptosis, which ultimately leads to intestinal PANoptosis. These findings provide a theoretical framework for understanding PEDV-induced intestinal injury in piglets and offer valuable insights for comparative medicine research.
    Keywords:  Oxidative stress; PANoptosis; PEDV; ZBP1
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2025.07.037
  3. bioRxiv. 2025 Jul 24. pii: 2025.07.24.666650. [Epub ahead of print]
      Poxviruses remain a significant global health concern, necessitating the development of novel antiviral strategies. Through high-throughput screening, we previously identified ciclopirox (CPX), an FDA-approved antifungal, as a hit that inhibits vaccinia virus (VACV) replication. Here, we further characterized its antiviral activity and mechanism of action using human primary fibroblasts. CPX significantly reduced VACV titers without reducing host cell viability, with an EC 50 in the sub-micromolar range and a CC 50 >500 μM. Rescue experiments demonstrated that CPX inhibits viral replication primarily through chelation of intracellular Fe 3+ and, to a lesser extent, Fe 2+ , as evidenced by partial restoration of viral replication with ferric ammonium citrate supplementation. Furthermore, overexpression of the iron-dependent enzymes RRM2 and the VACV-encoded F4L reduced the inhibitory effect of CPX, indicating that these host and viral proteins are affected by CPX treatment. Moreover, CPX treatment also suppressed cowpox virus and monkeypox (mpox) virus replication in vitro. It also reduced VACV titers in ex vivo mouse lung tissue. These findings highlight host iron metabolism as a critical determinant of poxvirus replication and support repurposing CPX as a broad-spectrum orthopoxvirus antiviral candidate.
    DOI:  https://doi.org/10.1101/2025.07.24.666650
  4. Mol Plant Pathol. 2025 Aug;26(8): e70133
      Replication-related protein A (RepA), encoded by the citrus chlorotic dwarf-associated virus (CCDaV), induces hypersensitive response (HR)-like cell death and defence responses. However, the interactions between the host plant and CCDaV-RepA remain unclear. In this study, Citrus limon chloroplast malate dehydrogenase (ClMDH) was found to interact with CCDaV-RepA in the nucleus. ClMDH induces perinuclear chloroplast clustering (PCC). Moreover, ClMDH suppressed HR-like cell death and the accumulation of reactive oxygen species (ROS) induced by CCDaV-RepA, and promoted the accumulation of CCDaV-RepA. In addition, CCDaV-RepA overexpression altered the subcellular localisation of ClMDH from the chloroplast to the nucleus and inhibited ClMDH-induced PCC. These results reflected the involvement of ClMDH-induced PCC in the host response to CCDaV infection and provide new insights into the interaction between the host and CCDaV.
    Keywords:  chloroplast malate dehydrogenase; citrus chlorotic dwarf‐associated virus; perinuclear chloroplast clustering; replication‐related protein A
    DOI:  https://doi.org/10.1111/mpp.70133