HSV-1 infection of the cornea causes a severe immunoinflammatory and vision-impairing condition called herpetic stromal keratitis (SK). The virus replication in corneal epithelium followed by neutrophil- and CD4+ T cell–mediated inflammation plays a dominant role in SK. Although previous studies demonstrate critical functions of type I IFNs (IFN-α/β) in HSV-1 infection, the role of recently discovered IFN-λ (type III IFN), specifically at the corneal mucosa, is poorly defined. Our study using a mouse model of SK pathogenesis shows that HSV-1 infection induces a robust IFN-λ response compared with type I IFN production at the corneal mucosal surface. However, the normal progression of SK indicates that the endogenous IFN responses are insufficient to suppress HSV-1–induced corneal pathology. Therefore, we examined the therapeutic efficacy of exogenous rIFN-λ during SK progression. Our results show that rIFN-λ therapy suppressed inflammatory cell infiltration in the cornea and significantly reduced the SK pathologic condition. Early rIFN-λ treatment significantly reduced neutrophil and macrophage infiltration, and IL-6, IL-1β, and CXCL-1 production in the cornea. Notably, the virucidal capacity of neutrophils and macrophages measured by reactive oxygen species generation was not affected. Similarly, ex vivo rIFN-λ treatment of HSV-1–stimulated bone marrow–derived neutrophils significantly promoted IFN-stimulated genes without affecting reactive oxygen species production. Collectively, our data demonstrate that exogenous topical rIFN-λ treatment during the development and progression of SK could represent a novel therapeutic approach to control HSV-1–induced inflammation and associated vision impairment.

The aggregation of β-amyloid peptides is a key event in the formative stages of Alzheimer’s disease. Promoting folding and inhibiting aggregation was reported as an effective strategy in reducing Aβ-elicited toxicity. This study experimentally investigates the influence of the external electric field (EF) and magnetic field (MF) of varying strengths on the in vitro fibrillogenesis of hydrophobic core sequence, Aβ16–22, and its parent peptide, Aβ1–42. Biophysical methods such as ThT fluorescence, static light scattering, circular dichroism, and infrared spectroscopy suggest that EF has a stabilizing effect on the secondary structure, initiating a conformational switch of Aβ16–22 and Aβ1–42 from β to non-β conformation. This observation was further corroborated by dynamic light scattering and transmission electron microscopic studies. To mimic in vivo conditions, we repeated ThT fluorescence assay with Aβ1–42 in human cerebrospinal fluid to verify EF-mediated modulation. The self-seeding of Aβ1–42 and cross-seeding with Aβ1–40 to verify that the autocatalytic amplification of self-assembly as a result of secondary nucleation also yields comparable results in EF-exposed and unexposed samples. Aβ-elicited toxicity of EF-treated samples in two neuroblastoma cell lines (SH-SY5Y and IMR-32) and human embryonic kidney cell line (HEK293) were found to be 15–38% less toxic than the EF untreated ones under identical conditions. Experiments with fluorescent labeled Aβ1–42 to correlate reduced cytotoxicity and cell internalization suggest a comparatively smaller uptake of the EF-treated peptides. Our results provide a scientific roadmap for future noninvasive, therapeutic solutions for the treatment of Alzheimer’s disease.

Herpes simplex virus type 1 (HSV-1) is a highly successful pathogen that primarily infects epithelial cells of the orofacial mucosa. After initial lytic replication, HSV-1 enters sensory neurons and undergoes lifelong latency in the trigeminal ganglion (TG). Reactivation from latency occurs throughout the host’s life and is more common in people with a compromised immune system. HSV-1 causes various diseases depending on the site of lytic HSV-1 replication. These include herpes labialis, herpetic stromal keratitis (HSK), meningitis, and herpes simplex encephalitis (HSE). HSK is an immunopathological condition and is usually the consequence of HSV-1 reactivation, anterograde transport to the corneal surface, lytic replication in the epithelial cells, and activation of the host’s innate and adaptive immune responses in the cornea. HSV-1 is recognized by cell surface, endosomal, and cytoplasmic pattern recognition receptors (PRRs) and activates innate immune responses that include interferons (IFNs), chemokine and cytokine production, as well as the recruitment of inflammatory cells to the site of replication. In the cornea, HSV-1 replication promotes type I (IFN-α/β) and type III (IFN-λ) IFN production. This review summarizes our current understanding of HSV-1 recognition by PRRs and innate IFN-mediated antiviral immunity during HSV-1 infection of the cornea. We also discuss the immunopathogenesis of HSK, current HSK therapeutics and challenges, proposed experimental approaches, and benefits of promoting local IFN-λ responses.

Newcastle disease (ND) is prevalent among the domesticated and the wild birds and is caused by the avian paramyxovirus serotype-I (APMV-I). It is commonly known to affect chicken, pheasant, ostrich, pigeon and waterfowl. Depending on the virulence, the velogenic NDV strains cause severe respiratory and nervous disorders with a high mortality rate. The live and killed vaccines are available for the prevention of infection in the market, but the drug for the treatment is not available. Nitazoxanide (NTZ), a member of thiazolides, is an antiparasitic drug. In the present study, the effect of NTZ on the NDV replication was explored. The experiments were conducted in chicken fibroblast cells (DF-1), PBMC, embryonated chicken eggs, and two-week old chickens. The inhibition of the NDV was observed upon post-treatment of NTZ at a concentration of~12.5 μM. Cytokine profiling of the DF-1, PBMC, and chicken embryonic tissue treated with NTZ revealed significant upregulation in all the cytokines studied except for IL-1β in DF-1 cells. It is plausible that NTZ is involved in causing immunemodulatory effects in poultry. NTZ treatment in two weeks old chicken showed significant reduction in NDV replication in trachea, and lungs, respectively, at 72 h post-infection. Encouraging results from the present study warrants repurposing NTZ as a drug for the treatment of viral infection in poultry. It will also pave the way towards understanding of similar effect against other animal pathogens.

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