Search Results (1,224)

HTLV-1 and HIV-1 represent biologically significant, structurally close, and equally problematic yet divergent human retroviruses. Although both infect CD4+ T cells and share similar structural elements, they differ markedly in genomic stability, transmission dynamics, clinical progression, and, most importantly, their transcriptional regulatory mechanisms. HTLV-1, an ancient virus with a limited global burden, often remains asymptomatic for decades before potentially causing ATL or HAM/TSP. Conversely, HIV-1, a relatively recent zoonotic transmission, undergoes rapid replication, exhibits high genetic diversity, and causes progressive immunodeficiency unless controlled by antiretroviral therapy (ART). At the molecular level, HTLV-1 maintains proviral latency through a balanced bidirectional transcription of regulatory genes (e.g., Tax and HBZ) that manipulate host transcription and immune evasion pathways, facilitating persistence and oncogenesis. HBZ and Tax were shown to contribute to driving the progressive acquisition of Treg-like and HLA class II phenotype in chronically activated CD4+ T-cells, promoting tolerogenic antigen presentation and immune evasion in ATL cells. This well-controlled differential expression of HTLV-1 regulatory genes is attributed to multiple intragenic virus regulatory mechanisms, which will be discussed in this review. In contrast, HIV-1 transcription is driven by a tightly regulated 5′ LTR promoter involving host factors such as NF-κB, Sp1, AP-1, and NFAT, among others, with strong influence imposed by the landscape of the provirus integration site, playing a pivotal role in latency and reactivation. The distinct regulatory circuitry of each virus suggests a key difference in their essential regulation, with HTLV-1 primarily relying on intragenic mechanisms, while HIV-1 relies more heavily on interactions with the surrounding host environment to control its expression. This difference underscores unique therapeutic challenges in managing viral latency, persistence, and pathogenesis. Full article

C-reactive protein (CRP) and serum amyloid A (SAA) are classical acute-phase proteins that exemplify humoral innate immunity, the soluble arm of the host’s first-line defense. Beyond their traditional use as biomarkers of inflammation, both proteins function as active effectors against pathogens by binding microbial components, activating complements, and modulating inflammation. However, bacteria, viruses, and fungi have co-evolved diverse mechanisms to cope with or evade these host defenses. This review aims to summarize the current understanding of CRP and SAA as soluble innate immune effectors and to highlight pathogen strategies to counteract their antimicrobial pressure. We systematically surveyed and summarized evidence from experimental and clinical studies describing “function of CRP and SAA during infection”, “CRP and SAA in innate immune defense”, and “evasion mechanisms across bacterial, viral, and fungal pathogens”. CRP and SAA are rapidly upregulated in response to infection and contribute to pathogen recognition, opsonization, and inflammation. Pathogens, however, employ multiple coping strategies, including surface modification to block CRP binding, proteolytic degradation of acute-phase proteins, shielding within biofilms, and subversion of host signaling. These countermeasures enable microbes to reduce immune clearance and promote persistence. CRP and SAA represent central elements of humoral innate immunity, shaping the outcome of host–pathogen interactions. Pathogen adaptations to these proteins illustrate an ongoing evolutionary arms race between host defense and microbial survival. A deeper understanding of these processes may open avenues for novel therapeutic approaches, such as targeting microbial evasion factors or enhancing host acute-phase responses. Full article

Background: Chemokine CCL5 may drive inflammation and vascular risk in advanced liver disease, but its cardiovascular implications are unclear. Secreted by hepatic, endothelial, macrophage, and lymphocytic cells, CCL5 is involved in cytokine regulation. Its serum levels rise in acute liver injury and hepatocellular carcinoma (HCC), but decline with fibrosis progression in end-stage liver disease (ESLD). CCL5 has also been linked to atherosclerosis. This study aimed to evaluate serum CCL5 levels in ESLD patients listed for liver transplantation (LT) and to assess their potential role as markers of cardiovascular (CV) risk and portal hypertension. Methods: We conducted an observational cohort study. Between 2019 and 2022, patients with ESLD evaluated for LT were enrolled. Data on liver pathology, CV risk, and laboratory parameters were collected. Serum CCL5 concentrations were measured using Sigma Aldrich^® CCL5 ELISA kits (MilliporeSigma, St. Louis, MO, USA). The database was analyzed with IBM^® SPSS^® Statistics version 20 (Chicago, IL, USA). Results: Overall, 46 patients were included, 50% with viral hepatitis and 28.3% with alcohol-related liver disease. HCC was present in 37% of cases. The median CV risk scores (CAD_LT = 7, mCAD_LT = 7, CAR_OLT = 18) placed the population at moderate CV risk. Serum CCL5 levels did not vary significantly between viral vs. non-viral cirrhosis (5511.8 vs. 6272.5 pg/mL, p = 0.15) and were not influenced by the presence of HCC (6098.4 vs. 5771.3 pg/mL, p = 0.55). We did not detect a correlation with MELD score (p = 0.21) or CV risk scores (CAD_LT: p = 0.58; mCAD_LT: p = 0.70; CAR_OLT: p = 0.22). Patients with thrombocytopenia (<100,000/µL, 54.3%) or a history of esophageal variceal ligation had lower CCL5 levels (5170.9 vs. 6750.8 pg/mL, p = 0.002 and 4252.0 vs. 6237.5 pg/mL, p = 0.003, respectively). Similarly, patients with a history of previous variceal bleeding and spontaneous bacterial peritonitis (SBP) had lower levels of CCL5 (4373.8 vs. 6119.9 pg/mL, p = 0.02 and 3404.3 vs. 6606.7 pg/mL, p = 0.01, respectively). We found a negative correlation between CCL5 and QTc interval duration (τ = −0.216, p = 0.037), left ventricle size (LV: τ = −0.235, p = 0.027), and pulmonary artery pressure (RV/RA gradient: τ = −0.225, p = 0.03). CCL5 correlated positively with the inflammatory markers C-reactive protein (CRP) (τ = 0.246, p = 0.018) and fibrinogen (r = 0.216, p = 0.04). Conclusions: In liver transplant candidates, serum CCL5 is not associated with cardiovascular risk scores or coronary atherosclerotic burden, but is inversely associated with clinical markers of portal hypertension severity. These findings suggest that CCL5 may serve as a potential non-invasive surrogate marker of portal hypertension rather than a cardiovascular risk biomarker in ESLD. Full article

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with uncertain etiology. Chronic viral infection, including Epstein–Barr virus (EBV), has been implicated as a potential driver of repetitive epithelial injury and dysregulated repair. We sought to evaluate and define the breadth versus specificity of EBV-directed humoral immunity in IPF. We performed proteome-scale serological profiling using an EBV protein microarray (202 proteins) representing all proteins expressed by the EBV proteome (type I and II) on plasma samples from 32 patients with confirmed IPF (87.5% male; mean age 60.9 years) and 15 healthy disease-free controls (40% male; mean age 57.9 years). Per-sample global EBV IgG means were higher in IPF than controls (Welch p = 0.005), and the difference persisted after sex adjustment (p = 0.012). Although no single antigen met a stringent FDR significance threshold, 10 EBV antigen-specific antibody responses showed nominal elevation in IPF, with 2 remaining nominally significant after sex adjustment and 5 additional antibody responses reaching significance only in linear regression models. Overall, these results support the concept that IPF is associated with a diffuse elevation of EBV-directed humoral responses rather than antigen-specific dominance, consistent with ongoing, low-level viral reactivation. The presence of an EBV-negative subgroup within the IPF cohort underscores etiological heterogeneity within IPF. Full article

RNA viruses are major pathogens in fish, causing high mortality and substantial economic losses in aquaculture. To uncover conserved antiviral mechanisms, we investigated the response of turbot (Scophthalmus maximus) to viral hemorrhagic septicemia virus (VHSV), infectious pancreatic necrosis virus (IPNV), and red-spotted grouper nervous necrosis virus (RGNNV) using a comparative proteomic approach complemented by in vivo and in vitro functional assays. Proteomic analyses revealed the central, conserved role of proteins involved in reactive oxygen species (ROS) production and redox homeostasis during early infection. Functional assays using head kidney-derived leukocytes identified neutrophils and macrophages as the primary ROS producers and showed that the modulation of cytoplasmic and mitochondrial ROS, as well as ROS-dependent DNA release, follows virus-specific patterns. The pharmacological inhibition of NADPH oxidase and mitochondrial ROS significantly affected viral replication, demonstrating the direct role of ROS in viral pathogenicity. Collectively, these findings highlight redox modulation as a conserved host response in teleost fish during RNA virus infection, linking oxidative stress regulation to viral progression. This knowledge provides a foundation for developing broad-spectrum therapeutic or preventive strategies to enhance disease resistance and promote sustainable aquaculture. Full article

The overlapping circulation of influenza (Flu), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; SC2), and respiratory syncytial virus (RSV) continues to challenge clinical laboratories, particularly in settings with limited automation and fragmented healthcare coverage. This study expanded the CDC Flu-SC2 assay by incorporating a laboratory-developed test (LDT) for RSV A/B detection into a fully automated quadruplex RT-qPCR (LDRA) on the Panther Fusion^® Open Access™ system. The design, based on more than 8000 RSV genomic sequences targeting the conserved M gene, achieved optimal amplification efficiencies (97–105%) and full multiplex compatibility. Analytical assessment established limits of detection between 9.6 and 37.8 copies per reaction, absence of cross-reactivity with 30 respiratory pathogens, and inclusivity for 32 viral variants. Commutability and diagnostic performance among the LDRA, CE IVD-marked Allplex™ SARS-CoV-2/FluA/FluB/RSV, and US IVD-marked Panther Fusion^® SARS-CoV-2/Flu A/B/RSV Assays were evaluated using 405 nasopharyngeal UTM-preserved swabs. The LDRA demonstrated excellent concordance (overall agreement ≥ 98%, κ > 0.95), strong diagnostic accuracy, and reliable detection of mixed infections. This quadruplex provides a fully automated, rapid, and accurate solution for the simultaneous detection of influenza A, influenza B, SARS-CoV-2, and RSV viruses, enhancing molecular diagnostic capacity and supporting equitable, timely clinical decision-making in middle-income healthcare systems such as that of the Dominican Republic. Full article

Red sea bream (Pagrus major) aquaculture represents one of the most economically important marine aquaculture industries in Japan and East Asia. However, viral diseases, particularly those caused by red sea bream iridovirus (RSIV), pose a serious threat to aquaculture production in this region. In this study, we applied high-hydrostatic-pressure (HHP) refolding technology to develop a recombinant vaccine targeting the RSIV major capsid protein (MCP). The recombinant MCP (RSIV-rMCP) expressed in Escherichia coli was insoluble; however, HHP treatment under alkaline (pH 10) conditions in the presence of arginine successfully solubilised the protein while preserving its structural integrity. The solubilised protein (HHP–RSIV-rMCP) induced strong RSIV-specific IgM responses and enhanced disease resistance in red sea bream. In contrast, sera from fish immunised with a commercial formalin-inactivated vaccine exhibited minimal reactivity to HHP–RSIV-rMCP but reacted significantly to formalin-treated HHP–RSIV-rMCP. These results indicate that the HHP–RSIV-rMCP vaccine induces conformation-specific IgM antibodies and that structural preservation is crucial for maintaining antigenicity. Collectively, our findings demonstrate that HHP refolding technology is an effective strategy for preparing structurally preserved antigens. Full article

Herpes simplex viruses (HSV-1 and HSV-2) are highly prevalent human pathogens that establish lifelong latency in sensory neurons, posing a persistent challenge to global public health. Their clinical manifestations range from mild, self-limiting orolabial lesions to severe, life-threatening conditions such as disseminated neonatal infections, focal encephalitis, and herpetic stromal keratitis, which can lead to irreversible corneal blindness. Beyond direct pathology, HSV-mediated genital ulcerative disease (GUD) significantly enhances mucosal susceptibility to HIV-1 and other sexually transmitted infections, amplifying co-infection risk and disease burden. Despite decades of clinical reliance on nucleoside analogues such as acyclovir, the therapeutic landscape has stagnated with rising antiviral resistance, toxicity associated with prolonged use, and the complete inability of current drugs to eliminate latency or prevent reactivation continue to undermine effective disease control. These persistent gaps underscore an urgent need for next-generation antivirals that operate through fundamentally new mechanisms. Marine ecosystems, the planet’s most chemically diverse environments, are providing an expanding repertoire of antiviral compounds with significant therapeutic promise. Recent discoveries reveal that marine-derived polysaccharides, sulfated glycans, peptides, alkaloids, and microbial metabolites exhibit remarkably potent and multi-targeted anti-HSV activities, disrupting viral attachment, fusion, replication, and egress, while also reshaping host antiviral immunity. Together, these agents showcase mechanisms and scaffolds entirely distinct from existing therapeutics. This review integrates emerging evidence on structural diversity, mechanistic breadth, and translational promise of marine natural products with anti-HSV activity. Collectively, these advances position marine-derived compounds as powerful, untapped scaffolds capable of reshaping the future of HSV therapeutics. Full article

Hepatitis B virus (HBV) persists in infected hepatocytes through covalently closed circular DNA (cccDNA), a stable episomal form that serves as the transcriptional template for viral replication. Accurate and sensitive quantification of intrahepatic cccDNA is crucial for evaluating antiviral therapies, particularly those targeting a functional cure. Here, we report the development of a novel, cccDNA-specific detection system combining recombinase polymerase amplification (RPA) with CRISPR/Cas12a-based fluorescence detection. We designed and validated CRISPR RNAs (crRNAs) targeting HBV cccDNA-specific regions conserved across genotypes A–D. Reaction conditions for both RPA and Cas12a detection were optimized to enhance sensitivity, specificity, and accuracy. The system reliably detected as few as 10 copies of cccDNA-containing plasmid per reaction and showed no cross-reactivity with non-cccDNA forms in serum or plasma, indicating assay specificity. When applied to liver tissue samples from 10 HBV-infected and 6 non-HBV patients, the RPA-CRISPR/Cas12a assay exhibited a high sensitivity (90%) and a strong correlation with qPCR results (R² = 0.9155), confirming its accuracy. In the conclusion, the RPA-CRISPR/Cas12a system provides a robust, cost-effective, and scalable platform for sensitive and specific quantification of intrahepatic HBV cccDNA. This method holds promises for research and high-throughput therapeutic screening applications targeting cccDNA clearance. Full article

Influenza A viruses remain a persistent global health challenge due to their rapid antigenic evolution, zoonotic potential, and pandemic threat. Universal countermeasures targeting conserved viral components are urgently needed to enhance diagnostic, surveillance, and therapeutic capabilities. Here, we report the generation and characterization of a high-affinity monoclonal antibody (2D8 mAb) against the nucleoprotein (NP) of the H9N2 avian influenza virus, a subtype with increasing relevance to human infections. Importantly, 2D8 mAb exhibited robust cross-reactivity with a broad spectrum of influenza A viruses, including H1, H3, H5, H7, and H9 subtypes, while showing no cross-reactivity with unrelated viral pathogens. Epitope mapping identified its binding target as a highly conserved NP motif ³⁸RFYIQMCTEL⁴⁷, which is invariant across all major human influenza A lineages. Isotyping revealed 2D8 mAb to be of the IgG2b/κ subclass, with an exceptionally high titer (1:20,480,000) as determined by ELISA. Given the essential role of NP in viral replication and host adaptation, this antibody offers a powerful platform for next-generation diagnostic assays capable of detecting a wide range of human and zoonotic influenza A viruses using a single reagent. Moreover, it holds potential for guiding the design of universal antiviral strategies targeting structurally constrained regions of the influenza virus. Our findings provide a valuable resource for advancing pan-influenza A interventions, with direct implications for improving pandemic preparedness and strengthening global influenza surveillance in both clinical and public health settings. Full article

Chicken respiratory diseases represent multifactorial conditions resulting from viral, bacterial, mycoplasmal pathogens, and environmental factors, causing significant economic losses within the poultry industry. A specific respiratory disease characterized by breathing difficulties and bronchial occlusion due to caseous exudates is termed chicken bronchial obstruction. However, the absence of rapid, precise, and highly sensitive diagnostic methods for differentiation of primary respiratory disease pathogens or opportunistic pathogens, including avian influenza virus (AIV), infectious bronchitis virus (IBV), Pseudomonas aeruginosa (P. aeruginosa), and Escherichia coli (E. coli), constitutes a substantial challenge. This study developed a quadruplex droplet digital polymerase chain reaction (ddPCR) method that targeted the HA gene of H9 subtype AIV, the M gene of IBV, the Pal gene of P. aeruginosa, and the UidA gene of E. coli. Following the optimization of annealing temperature, sensitivity, and repeatability, the minimum detectable concentrations were determined as 3.02 copies/μL for the HA gene of H9 subtype AIV, 3.08 copies/μL for the M gene of IBV, 3.19 copies/μL for the Pal gene of P. aeruginosa, 3.39 copies/μL for the UidA gene of E. coli. No cross-reactivity was observed with Newcastle disease virus (NDV), H5 subtype AIV, H7 subtype AIV, fowl adenovirus serotype 4 (FAdV-4), infectious laryngotracheitis virus (ILTV), Avibacterium paragallinarum, Streptococcus, Salmonella, Pasteurella multocida, and Staphylococcus aureus. The method demonstrated excellent repeatability, with a coefficient of variation (CV) below 9%. The 185 clinical samples collected in Hebei Province China are tested by both quadruplex ddPCR and quadruplex qPCR method and the results compared. The sensitivity of the quadruplex ddPCR method (57.30%; 106/185) slightly exceeded that of the quadruplex qPCR method (49.73%; 92/185). Pathogens or opportunistic pathogens positive rates obtained via the quadruplex ddPCR were 40.00% for H9 subtype AIV, 33.51% for IBV, 24.32% for P. aeruginosa, and 27.57% for E. coli. In comparison, the positive rates of H9 subtypes AIV, IBV, P. aeruginosa, and E. coli from the quadruplex qPCR were 36.22%, 30.81%, 21.62%, and 24.32%, respectively. The coincidence rates between the two methods were 96.22% for H9 AIV, 97.30% for IBV, 97.30% for P. aeruginosa, and 96.76% for E. coli. These results demonstrated that the quadruplex ddPCR method represented a highly sensitive, specific, and rapid technique for identifying H9 subtype AIV, IBV, P. aeruginosa, and E. coli. Full article

Emerging evidence suggests that viral infections may contribute to the onset and progression of Alzheimer’s disease (AD) and other forms of dementia. Understanding the mechanism of viral involvement in the pathogenesis of AD and related dementia (ADRD) could contribute to reducing the burden caused by these conditions, which affect a large portion of the aging population. Some studies indicate the link between AD and viral infections, notably coronaviruses and herpesviruses. In AD, excessive production of reactive oxygen species (ROS) results in the modifications of lipids, proteins, and nucleic acids, contributing to synaptic dysfunction and cognitive impairments. Experimental evidence suggests that viral infections linked to ADRD induce the cellular production of ROS, possibly contributing to the pathogenesis of these conditions. Despite significant advances in defining the roles of ROS in neurological disorders and viral infections, the specific roles of ROS in virus-associated ADRD have not been thoroughly investigated. The main objective of this review article is to comprehensively provide information on the experimental evidence for the production of ROS by viruses to help the readers investigate the role of ROS in the relationship between viral infections with ADRD. Full article

Bovine gammaherpesvirus 4 (BoGHV-4) is an opportunistic uterine pathogen whose reactivation is associated with postpartum inflammation and bacterial lipopolysaccharide (LPS). Platelet-rich plasma (PRP) is a regenerative biotherapeutic capable of modulating inflammatory responses, although its effects may vary depending on BoGHV4 genotype. In this study, primary bovine endometrial cells (BECs) were cultured in medium containing 10% PRP instead of fetal bovine serum, infected with two genetically divergent BoGHV-4 isolates (07-435, genotype 3; 10-154, genotype 2), and subsequently stimulated with bacterial lipopolysaccharide (LPS, 100 ng/mL). Expression of the viral immediate-early gene IE-2 and host immune genes (TLR4, TNF-α, CXCL8, and IFN-γ) were quantified by RT-qPCR from 4 to 48 h after stimulation. Isolate 07-435 induced a sustained activation of IE-2 and gradual cytokine upregulation, while isolate 10-154 elicited an early but transient inflammatory response followed by gene downregulation. PRP did not modify the strain-specific patterns of viral and inflammatory gene expression but established a common inflammatory baseline, whereas the magnitude and temporal profile of the response continued to be dictated by the viral genotype. These findings indicate that BoGHV-4 genotypic diversity remained the main determinant of response intensity and duration, supporting PRP as a context-dependent rather than a universal antiviral modulator. Full article

Varicella-zoster virus (VZV) is a human neurotropic herpesvirus. The primary infection with VZV causes chickenpox and establishes latency in sensory and dorsal root ganglia. Viral reactivation leads to herpes zoster (HZ), which is accompanied by complications such as postherpetic neuralgia (PHN), causing a significant disease burden. At present, vaccination is the most effective preventive measure. We developed a recombinant zoster vaccine, gE/BFA01, which comprises truncated VZV glycoprotein E and the liposome-based adjuvant BFA01 (containing MPL and QS-21). In this study, we evaluated the recombinant zoster vaccine’s immunogenicity in a live attenuated VZV-primed C57BL/6N mouse model and explored the mechanism of action of the BFA01 adjuvant. The results indicate that the gE/BFA01 vaccine induces superior antibody responses and stronger cellular immune responses compared with gE with aluminum hydroxide. Furthermore, gE/BFA01 showed comparable immunogenicity to the licensed vaccine Shingrix. Mechanistic investigations revealed that the BFA01 adjuvant can enhance the recruitment of innate immune cells at the injection site, increase the expression of DCs surface maturation markers, and activate multiple inflammatory signaling pathways in lymph nodes. Collectively, these findings indicate that gE/BFA01 can induce potent humoral and cellular responses, supporting its further development as a high-efficiency vaccine candidate. Full article

Polyomavirus-associated nephropathy was first reported over 50 years ago. However, it still represents a cause of renal injury in kidney transplant recipients, particularly in the first two years post-transplantation, with occurrence rates of 1–10%. The role played by immunosuppression in viral reactivation is well acknowledged, and the modulation of its level is the main strategy for clinical management. Viral and immunological evaluation are fundamental for optimizing its diagnostic and therapeutic pathway. In this review, the main features of BK polyomavirus and associated nephropathy in renal transplant patients are addressed and discussed from a virological point of view; the role of BK polyomavirus in hematopoietic stem cell transplantation and other solid-organ transplant patients is also briefly reported. Full article