Herpes simplex virus-1 (HSV-1) is a neurotropic virus that can infect the brain, and an uncontrolled infection can lead to severe encephalitis. NO can exert both antiviral as well as cytotoxic effects in the central nervous system (CNS) depending on its concentration and site of infection. In this study, we report that treatment of an intranasal murine HSV-1 infection with aminoguanidine (AMG) decreases both neuroinflammation and neurodegeneration markers, but its positive effect depends on the time of treatment. Specifically, early treatment with AMG impaired the activation of microglia/monocytes, leading to decreased virus-specific antiviral response and higher viral titers in the brain. However, AMG treatment during the peak of brain infection significantly improved antiviral response, reduced inflammation and improved general clinical score. We also found that treatment with AMG decreased beta amyloid levels during both primary and latent infections and protected from the accumulation of phosphorylated Tau protein during early infection. Our findings position inducible nitric oxide synthetase (iNOS) as a potential therapeutic target for mitigating virus-induced neuroinflammation and neurodegeneration.

Many studies have shown an association between herpes simplex virus type 1 (HSV-1) infection and the development of neurodegeneration processes later in life, such as Alzheimer’s disease. The Fas/FasL death pathway plays an important role in the complex regulation of the local inflammatory response and mounting of the specific antiviral response in HSV-1 infection. Here, we applied a mouse model of latent HSV-1 neuroinfection to Fas- and FasL-deficient mice (lpr and gld) to explore whether the lack of functional Fas/FasL pathway protects from inflammation-related neurodegeneration. The latently infected Fas- and FasL-deficient mice (lpr and gld) were not protected from virus replication despite the accumulation of virus-specific cytotoxic T cells. However, the lack of Fas/FasL pathway decreased neuroinflammation- and neurodegeneration-related markers, including cognitive impairment, amyloid-β protein, and tau hyperphosphorylation. The use of a glucocorticoid, dexamethasone, to decrease neuroinflammation in wild-type mice did not protect from cognitive impairment, despite the improved antiviral response. Our data indicate that excessive neuroinflammation via the Fas/FasL pathway during HSV-1 infection is associated with neurodegeneration. Furthermore, the administration of immunomodulatory agents to ameliorate the outcome of HSV-1 latent infection should be restricted to the peak of neuroinflammation.

Municipal wastewater catchments are significant sources of symbiotic, opportunistic, and drug-resistant bacteria that can acquire or enhance their resistance. This “re-emergence of threats” presents a serious public health issue, especially during crisis conditions (COVID-19). The aim of this study was to propose a sampling algorithm, identify strategically important sites within the wastewater catchment, expand the range of bacterial indicators, and rapidly confirm potential threats using in vitro diagnostics in both raw and treated sewage. A parallel objective was to evaluate the effectiveness of sequencing methods in pre-epidemic studies. The research was conducted as part of a long-term surveillance program at transportation hubs, healthcare facilities, residential complexes, and wastewater treatment plants in Warsaw, Poland. Total nucleic acid (TNA) was isolated from samples, amplified using qPCR kits, and selected samples underwent next-generation sequencing. In raw sewage, the most frequently detected regions included sequences complementary to the bacterial vanB gene, the Integron Verona-encoded metallo-β-lactamase (VIM) gene, and markers for Mycobacterium tuberculosis. Treated environmental effluents primarily contained DNA fragments complementary to the bacterial vanB sequence, along with genes related to resistance against oxacillin and imipenem, as well as the VIM gene and Legionella sp. 16S rRNA sequencing of the sewage samples revealed the presence of 12 promising bacterial indicators relevant to public health and environmental hygiene. The proposed algorithm aligns with the provisions of EU Directive 2024/3019 and in vitro diagnostic tests demonstrated the potential and utility of rapid screening analyses of wastewater during disruptions or crises, as well as in situations involving equipment shortages and logistical challenges in healthcare. The proposed expanded range of bioindicators could expedite decision-making regarding preventive measures and medical support for various counties, hospitals, and transportation hubs in large urban areas. The sequencing results further emphasized the need to broaden the scope of the bacterial indicators for environmental surveillance.