bims-mevinf 2025-12-28 papers

Poult Sci. 2025 Dec 16. pii: S0032-5791(25)01534-2. [Epub ahead of print]105(2): 106294

PERK-eIF2α activation by avian reticuloendotheliosis virus: a dual strategy to suppress apoptosis and aggravate immunosuppression for enhanced replication.

Yitong Wang, Yike Xing, Ziqiang Cheng, Wanqing Xu, Chengui Li, Guihua Wang.

Viral infection induces endoplasmic reticulum stress (ERS) and the subsequent unfolded protein response (UPR), which play a pivotal role in viral replication and pathogenesis. However, the specific implications of ERS in REV infection remain poorly defined. In this study, we demonstrate that reticuloendotheliosis virus (REV) infection induces significant endoplasmic reticulum (ER) swelling and upregulates the expression of the ERS marker HSPA5 in DF-1 cells. By modulating ERS, we found that the ERS activation significantly promoted REV replication. Further investigation reveals that among the UPR signaling pathways, the PERK branch was specifically activated in REV-infected cells, as indicated by a significant increase in phosphorylated PERK and its downstream target, eukaryotic translation initiation factor 2α (eIF2α). We subsequently established that activation of the PERK-eIF2α signaling axis promotes REV replication. Concurrently, REV-triggered PERK-eIF2α activation attenuated apoptotic cell death and exacerbated immunosuppression. In conclusion, this study demonstrates that REV infection induces ERS in DF-1 cells, leading to specific activation of the PERK-eIF2α signaling axis. The PERK-mediated response facilitates viral replication by simultaneously suppressing apoptosis and aggravating immunosuppression.

Keywords: PERK-eIF2α signaling axis; REV; UPR pathway; endoplasmic reticulum stress; virus replication

DOI: https://doi.org/10.1016/j.psj.2025.106294

Front Microbiol. 2025 ;16 1609598

Modulation of viral replication, autophagy and apoptosis by induction and mutual regulation of transcription factors EB and E3 during coronavirus infection.

Bei Yang, To Sing Fung, Lixia Yuan, Rui Ai Chen, Ding Xiang Liu.

Viral invasion and replication in cells significantly impact lysosome structure and function. By sensing changes in the lysosome status, cascades of cellular responses are triggered to maintain lysosomal homeostasis. Two key regulators, transcription factors EB (TFEB) and E3 (TFE3), play essential regulatory roles in these processes by shuttling between the cytoplasm and the nucleus. In this study, we report that infection of cells and/or chickens by gammacoronavirus infectious bronchitis virus (IBV), human betacoronavirus OC43 (HCoV-OC43), and alphacoronavirus porcine epidemic diarrhea virus (PEDV) upregulates the expression of TFEB/TFE3 as well as their downstream targets, and induces the lysosomal stress response. Knockdown of TFE3 alone or together with TFEB demonstrated a pronounced role played by TFE3 in regulating viral replication, virus-induced autophagy and apoptosis in cells infected with the three viruses, and a synergistic effect of TFEB and TFE3 in cells infected with IBV and HCoV-OC43. Furthermore, inhibition of the biosynthetic secretory pathway with brefeldin A (BFA) demonstrated that the release of HCoV-OC43 is mainly via the lysosomal pathway. This study provides novel insights into the functional roles of the lysosomal biogenesis and stress response in coronavirus replication and virus-host interactions.

Keywords: TFE3; TFEB; apoptosis; coronaviruses; lysosomal stress response

DOI: https://doi.org/10.3389/fmicb.2025.1609598

Virulence. 2026 Dec;17(1): 2609397

Metabolic control of macrophages in coronavirus disease 2019.

Li An, Houxi Xu, Qiaoling Fan, MengJiang Lu, Dongdong Sun.

In the context of COVID-19, macrophages are primarily responsible for sensing and responding to the virus, significantly influencing disease outcomes. They are involved in early pathogen recognition, immune activation, and tissue repair. Heterogeneity and phenotypic plasticity of macrophages are dynamically shaped by microenvironmental cues, including metabolites, hypoxia, and pathogen-derived signals. Notably, emerging evidence underscores that cellular metabolism, particularly in macrophages, dictates immune responses to viral infection. This metabolic-immune crosstalk critically determines COVID-19 severity, ranging from viral clearance to hyperinflammation or fibrosis. In this review, we systematically dissect how cell-intrinsic metabolic nodes and extrinsic factors modulate macrophage effector functions, while illustrating the complications associated with macrophage metabolic dysregulation in SARS-CoV-2 infection. These mechanistic insights provide a rational foundation for therapeutic strategies targeting macrophage metabolism to rebalance immune responses and mitigate COVID-19 complications.

Keywords: COVID-19; COVID-19 implications; SARS-CoV-2; macrophages; metabolism

DOI: https://doi.org/10.1080/21505594.2025.2609397

J Agric Food Chem. 2025 Dec 23.

Rice Fatty Acid Desaturase OsFAD6 Confers Antiviral Resistance against RBSDV through MAPK and Hormone Signaling.

Jianjian Liu, Yange Zhao, Pengyue Wang, Xinxin Jing, Meirong Xiang, Keda Han, Dongyu Zhai, Pengbai Li, Honglian Li, Zujian Wu, Chaonan Wang, Songbai Zhang, Chao Zhang.

Fatty acids (FAs) are crucial for plant defense against pathogens. While unsaturated fatty acids (UFAs), synthesized by fatty acid desaturases (FADs), are established mediators of resistance against bacterial and fungal pathogens, their involvement in regulating virus infection remains poorly understood. Here, we demonstrate that OsFAD6, a chloroplast-localized fatty acid desaturase, confers resistance to rice black-streaked dwarf virus (RBSDV). RBSDV infection significantly suppresses OsFAD6 expression, suggesting viral targeting of this defense component. Functional analyses using OsFAD6-overexpressing and knockout rice lines established that OsFAD6 enhances resistance to RBSDV. Transcriptomic profiling revealed that OsFAD6 enhances antiviral defense through modulation of the MAPK signaling cascade and reprogramming of multiple hormone signaling pathway-associated genes. Furthermore, OsFAD6 can be degraded by RBSDV P5-2 through the autophagy pathway. These findings identify OsFAD6 as a novel antiviral component in rice and provide new molecular targets for breeding virus-resistant rice varieties.

Keywords: MAPK signaling pathway; OsFAD6; antiviral defense; fatty acids; rice black-streaked dwarf virus

DOI: https://doi.org/10.1021/acs.jafc.5c09595

Antiviral Res. 2025 Dec 24. pii: S0166-3542(25)00264-5. [Epub ahead of print] 106338

2-Deoxy-D-glucose attenuates lipopolysaccharide-induced inflammation and restricts Zika, Chikungunya, and Mayaro virus replication in monocyte-derived macrophages.

Y S Tamayo-Molina, Yisel García-Marin, Silvio Urcuqui-Inchima.

Re-emerging arthropod-borne viruses such as Mayaro (MAYV), Chikungunya (CHIKV), and Zika (ZIKV) pose a growing global health concern as Aedes mosquito populations expand. These arboviruses infect innate immune cells, particularly monocyte-derived macrophages (MDMs), which support viral replication and serve as reservoirs that facilitate dissemination. Because no effective antiviral treatments are available, strategies that modulate macrophage responses and restrict viral replication are urgently needed. Here, we evaluated the immunomodulatory and antiviral effects of 2-deoxy-D-glucose (2-DG) in human MDMs. First, we assessed how 2-DG shapes transcriptional responses to lipopolysaccharide (LPS), a canonical TLR4 agonist. Co-treatment with 2-DG and LPS induced genes linked to inflammatory, antiviral, and endoplasmic reticulum (ER) stress pathways. Notably, IL10 mRNA and IL-10 protein displayed an inverse relationship with metabolic stress yet correlated positively with inflammatory and antiviral gene expression, whereas GADD34 was positively associated with both inflammatory and ER stress responses, suggesting an integrative regulatory role. We next investigated whether 2-DG pretreatment limits replication of MAYV, CHIKV, and ZIKV in infected MDMs. Antiviral assays demonstrated that 2-DG reduced replication of all three arboviruses by approximately one log10. Additional analyses revealed distinct temporal sensitivities: MAYV and CHIKV showed early and late susceptibility, whereas ZIKV exhibited a distinct kinetic profile. Mechanistic experiments confirmed that 2-DG acts post-entry primarily and reverses the antiviral phenotype observed in LPS-primed MDMs. Collectively, these findings reveal crosstalk among inflammatory, antiviral, and ER stress pathways and demonstrate that 2-DG modulates LPS-driven inflammation while reducing replication of pathogenic arboviruses in human MDMs.

Keywords: 2-deoxy-D-glucose; Antiviral; Arbovirus; ER stress; Inflammatory; Lipopolysaccharide

DOI: https://doi.org/10.1016/j.antiviral.2025.106338