Verapamil HCl is known to suppress infections caused by several viruses, including respiratory syncytial virus, bovine herpesvirus 1, and SARS-CoV-2. However, the potential anti-PRRSV mechanisms of Verapamil HCl remain unknown. This study demonstrates that Verapamil HCl exerts anti-PRRSV effects by attenuating the Ca2+ imbalance induced by PRRSV. Furthermore, Verapamil HCl can promote interferon-mediated antiviral responses and reduce pro-inflammatory factor production during PRRSV infection via p38/Nrf2/Keap-1/HO-1 axis activation. These findings indicate that Verapamil HCl could be a very effective treatment agent against PRRSV.

Human retinoic acid-inducible gene I deficiency is associated with susceptibility to classic Kaposi sarcoma.

The role of the circadian clock gene cry1 in the regulation of the antiviral response in zebrafish (Danio rerio) larvae.

The conserved long noncoding RNA LTCONS12135 positively regulates innate immunity in teleost.

Immune responses are key in controlling viral infections such as HIV-1, which remains a global challenge to public health. X/Y-chromosome-encoded genes and sex steroid hormones can modulate immune cells and drive distinct patterns of gene and protein expression involved in antiviral function, impacting sex-dependent immune responses and altering the balance of specific immune pathways. These sex-specific differences in antiviral immune responses have significant consequences for the outcome of HIV-1 infection. A better understanding of sex differences in HIV-1-specific antiviral immunity is required to implement and develop new strategies for prevention, treatment and ultimately a functional cure against HIV-1. Here we review the impact of X- and Y-encoded genes and the role of sex steroid hormones on modulating antiviral immune responses against HIV-1 and the consequences for disease manifestations in people living with HIV-1.

The role of IRF1 in positive feedback of type I IFN transcription to combat Siniperca chuatsi rhabdovirus (SCRV) infection in teleost fish.

BmC-LZM-like2/4 mediates antiviral defense against BmNPV via dorsal pathway.

Viral pathogens pose an emerging threat to the sustainability of insect mass-rearing systems, yet they remain understudied in key species like the black soldier fly (BSF; Hermetia illucens). Although multiple viral sequences have been reported in BSF, their role in disease has not been established until now. Here, we provide the first in vivo characterization of H. illucens solinvivirus (HiSvV), confirming its role as a viral entomopathogen of BSF. Metatranscriptomic analysis of a diseased colony revealed a high viral load attributable to HiSvV. We successfully isolated the virus and developed injection- and oral-based infection assays to investigate replication, tissue tropism, transmission and risk of mortality. HiSvV replicated in inoculated adults, induced premature mortality in flies and was transmitted both horizontally and vertically. Infected flies also mounted a broad antiviral response, which supported active pathogenesis, even if the small RNA pathways were not activated. These findings establish HiSvV as the first confirmed viral pathogen of BSF and underscore the urgent need for viral surveillance and experimental tools to safeguard industrial insect rearing.

Transcriptome analysis and exploration of immune key genes of hepatopancreas after Poly(I:C) stimulation in Amphioctopus fangsiao.

RNase L regulates the antiviral proteome by accelerating mRNA decay, inhibiting nuclear mRNA export, and repressing transcription.

The vesicle trafficking system enables multidirectional cargo fluxes between endomembrane compartments. However, vesicle trafficking plays dual roles during pathogen infections. In plants, it mediates autophagic immune responses but can also be hijacked by pathogens to facilitate successful infections. We demonstrate that vesicle trafficking machinery acts as a double-edged sword during infection by the geminivirus tomato yellow leaf curl Sardinia virus (TYLCSaV) in Nicotiana benthamiana. Virus-induced gene silencing of eight genes encoding key vesicle trafficking regulators revealed contrasting outcomes. Silencing of NbSAR1 and NbAP-1γ significantly increased systemic geminiviral DNA accumulation, whereas silencing of Nbδ-COP, NbARF1 and clathrin genes almost completely abolished infection. Notably, this inhibition is hypothesized to result from direct or indirect impairment in viral movement, as replication remained unaffected by gene silencing. The observed effects affect other geminiviruses, including tomato yellow leaf curl virus (TYLCV) and beet curly top virus (BCTV), but not unrelated pathogens, such as the RNA potato virus X (PVX) or the plant pathogenic bacterium Pseudomonas syringae. These findings suggest that while the vacuolar and autophagy branches of the vesicle trafficking system might mediate antiviral autophagic defence responses, the integrity of endocytosis and retrograde transport is essential for systemic geminiviral infection.

Multiple sclerosis-associated EBNA2 variants influence the response to peginterferon beta-1a therapy.

Emerging roles of IL-9 and Th9 cells in respiratory viral illnesses.

Transcriptome analysis reveals the response mechanism of largemouth bass (Micropterus salmoides) brain to MSRV infection.

Midnolin has an ancient origin and negatively regulates type I IFN response in teleost fish.

Rotavirus induces mucosal B-cell responses through the TLR3/TRIF and MAVS pathways.

Low-pathogenic avian influenza (LPAI) virus H9N2 has been endemic in Bangladesh since 2006. While the molecular epidemiology and pathogenicity of circulating tribasic H9N2 viruses are well-documented in chickens, data on pathogenicity in quails remain limited. Given the fact that quails serve as potential mixing vessels for avian influenza viruses, understanding of currently circulating tribasic H9N2 viruses' pathobiology is crucial. The aim of this work was to observe pathogenicity, including clinicopathological changes, virus shedding, and cytokine expression of the recent circulating tribasic H9N2 virus-infected Japanese quails in Bangladesh. A total of 64 quails were randomly assigned into two groups: an infected group (n = 32) and a control group (n = 32). Infected quails (at 4 weeks) received 500µL of virus (106 EID50/mL) via the oculo-nasal route. Quails were subsequently monitored for clinicopathological changes, virus shedding, and cytokine expression at various intervals until 70 days of age. Infected quails exhibited decreased egg production (7%-24%) and reduced weight gain (5%-12%) compared to controls, though no mortality was observed. Gross lesions included congestion and mild-to-moderate haemorrhages in the trachea, lungs, intestine, and kidney until 10 days post-infection (dpi). Histopathology revealed mild tracheitis, pneumonia, slight haemorrhages and degenerative kidney changes at different dpi. The virus replicated prominently in the trachea, lungs, intestine, and kidney up to 5 dpi, with peak shedding via the oropharyngeal route. Following infection, IL-8, TNF-α, IFN-β, and IFN-γ were expressed in the trachea, lungs, intestine, and lymphoid organs at 2, 5, 10, and 15 dpi. Proinflammatory cytokine TNF-α was upregulated to the significantly higher levels (p ≤ 0.001) in trachea and lungs at 10 dpi in tribasic H9N2-infected quails compared to non-infected control group. Notably, quails exhibited a robust early antiviral response (IFN-β and IFN-γ on 2 dpi) against H9N2 infection except for lymphoid tissues regarding IFN-γ. This study gives valuable insights into host-pathogen interaction and confirms that the circulating tribasic H9N2 virus remains phenotypically low pathogenic in Japanese quails in Bangladesh but cause long-term impairment of important productivity parameters (weight gain, laying rates).

Dual roles of USP39 in stabilizing PB2 and orchestrating ribonucleoprotein assembly drive H5 influenza virus replication and pathogenicity.

Background/Objectives: FAM111A is a trypsin-like serine protease that has emerged as a regulator of DNA replication, and is directly related to genome stability, protein homeostasis, antiviral defense and cancer progression. Pathogenic variants in FAM111A are correlated with genetic syndromes such as Kenny–Caffey syndrome type 2 (KCS2) and gracile bone dysplasia/osteocraniostenosis (GCLEB/OCS). This study focuses on the evolutionary, genetic, and structural analysis of FAM111A, in order to identify key regions and candidate pharmacological targets that are related to this enzyme’s function. Methods: The methodology of this in silico study includes separate analyses at the sequence, structural and functional levels. Initially, data mining was carried out using NCBI/Protein (2025), and then data filtering was performed in order to identify representative FAM111A sequences for several species. Sequence analysis was then executed through multiple alignments and phylogenetic analyses. Through this, conserved domains and motifs were identified. For structural analysis, human pathogenic mutations and protein structures were identified through searches in biological databases including PDB and ClinVar, and then all data were analyzed in order to identify candidate pharmacological targets related to FAM111A function. Results: Approximately 1850 FAM111A protein sequences were retrieved for several species, and after filtering processes a dataset of 85 representative sequences was generated. Evolutionary analysis indicates that FAM111A originated in early metazoans, with progressive domain specialization leading to mammal-restricted acquisition of regulatory elements, including the PIP-box PCNA (proliferating cell nuclear antigen) interacting peptide and UBL (ubiquitin-like) domains. The ubiquitin-like/DNA binding domain and catalytic serine protease domain (SPD) are the most conserved, containing seven highly conserved motifs. The structural analysis was based on two protein structures and 34 critical mutations that accumulate in two distinct regions. Finally, by combining the results, six pharmacological targets and 100 inhibitors are proposed. Conclusions: Advancing the structural and function characterization of FAM111A, coupled with pharmacological target identification and evolutionary insights, will be critical to validate this underexplored protease as a therapeutic genetic target in genetic disorders, cancer, and antiviral responses.

Introduction The gut microbiota plays a central role in shaping systemic immunity and modulating the gut–lung axis, which is crucial during respiratory infections such as COVID-19. SARS-CoV-2 infection is known to disrupt the gut microbiome, but the downstream functional impacts on microbial metabolism and host immune responses remain insufficiently understood. Methods Using K18-hACE2 transgenic mice, researchers investigated the effects of SARS-CoV-2 variants (WA and Omicron) on the gut microbiome and host immunity. Microbial composition and functional profiles were assessed post-infection. To test the therapeutic potential of Akkermansia muciniphila ( A. muciniphila ), live bacteria were administered prophylactically, and various outcomes were evaluated, including weight loss, lung pathology, immune cell phenotypes, and cytokine production. Results In K18-hACE2 transgenic mice infected with SARS-CoV-2, there was a marked reduction in gut microbial diversity, accompanied by a consistent enrichment of A. muciniphila . This microbial shift was associated with functional disruptions in key metabolic pathways, particularly those involved in glycosaminoglycan degradation and lipid metabolism, suggesting a broader impact of infection on microbial functionality. Remarkably, prophylactic administration of live A. muciniphila prior to infection led to significant protective effects. Treated mice exhibited reduced weight loss and improved lung histopathology compared to untreated controls. Local antiviral immune responses in the lung were notably enhanced without triggering excessive systemic inflammation. Mice receiving A. muciniphila also demonstrated elevated production of Th2 and Th17 cytokines, robust expansion of tissue-resident memory T cells, and the formation of inducible bronchus-associated lymphoid tissue (iBALT)—all indicative of potentiated mucosal immunity. These findings highlight a functional role for A. muciniphila not only as a microbial signature of COVID-19-associated dysbiosis but also as an active modulator of host immune responses during respiratory viral infections. Discussion These findings position A. muciniphila as both a biomarker of COVID-19-related gut dysbiosis and a potent live biotherapeutic candidate for respiratory infections. Its ability to enhance mucosal immune responses through gut–lung axis modulation highlights its promise in prophylactic strategies against viral respiratory diseases, including SARS-CoV-2.