Findings suggest that to adequately serve farmers, medical students interested in entering practice in rural areas should have or develop a relevant and adequate understanding of farming practices.
Background: Over 60% of the United States population is infected with herpes simplex virus 1 (HSV-1). Current HSV-1 treatment regimens exert their antiviral effects through a common mechanism of action and suffer from high dosing frequencies, which may contribute to patient noncompliance and the subsequent development of antiviral resistance. Although primarily known for their functions in maintaining homeostatic control of arterial blood and osmotic pressures, components of the Renin-Angiotensin Aldosterone System (RAAS) have been implicated in viral replication and some components demonstrated antiviral properties. However, the antiviral properties of RAAS components have not been well characterized in reference to HSV-1. Methods: To address this gap in knowledge, we evaluated the antiviral effects of captopril, an Angiotensin Converting Enzyme 1 (ACE-1) inhibitor, on HSV-1 infection in SH-SY5Y neuroblastoma cells. We demonstrated that captopril attenuates HSV-1-induced cytopathic effects (CPE) via cell-based and morphological assays. To investigate the potential mechanism, we conducted molecular modeling studies and identified the ability of captopril to interact with and bind HSV-1 glycoprotein D. To determine where in the virus life cycle captopril exerts its protective effects, we performed experiments observing the effect of captopril on both viral entry and replication utilizing a green fluorescent protein-tagged virus and subsequent quantitative Polymerase Chain Reaction. Results: Results suggest captopril protects cells from HSV-1-induced CPE through its effect on viral replication by increasing cell viability in infected cells and decreasing virus replication, which we propose is modulated through the decreased expression of ICP0. Conclusions: Collectively, the results presented here support further evaluation of captopril, and other RAAS components, as a basis for potential novel therapeutic interventions for the treatment of HSV-1, its associated pathologies, and potentially other virus infections.
Over 60% of the United States population is infected with HSV-1, a double-stranded DNA virus belonging to the Herpesviridae family. HSV-1 is continually documented as a leading infectious cause of corneal blindness and encephalitis. Members of the herpesviridae family have been implicated as cardiovascular pathogens and are independently associated with the future risk of cardiovascular death. Investigations have demonstrated that hypertension may be significantly related to inflammation, a major symptom of HSV-1 infection. Most HSV-1 antivirals are nucleoside analogs which are effective for individuals experiencing current outbreaks, but are limited by the development of antiviral resistance. Thus, there is a need for novel antiviral targets to decrease viral reactivation, a major player in viral associated neuropathologies. In addition to its well-known function of maintaining homeostatic control of arterial and osmotic pressure, components of the Renin Angiotensin System (RAS) have been demonstrated to exert antiviral functions. RAS targets, such as angiotensin peptides and angiotensin type 1 receptors, have been evaluated for their antiviral properties. Yet, the antiviral properties of other currently approved RAS inhibitors have not been investigated. To determine if other RAS components may inhibit viral activity, we tested the hypothesis that captopril, an inhibitor of angiotensin converting enzyme 1 (ACE), attenuates cytopathic effects of HSV-1 in SH-SY5Y, human neuroblastoma, cells. Photomicrographs of SH-SY5Y cells demonstrated that captopril protects cells from HSV-1-induced cytopathic effects. Additionally, cell viability assays revealed that captopril reduced HSV-1-induced cellular death by 18% (p-value<.05, compared to vehicle treated HSV-1 infected cells). Preliminary viral entry assay data suggests captopril may exert antiviral effects through entry inhibition as demonstrated by a 14.18% decrease in GFP immunofluorescence after captopril-treated cells were exposed to a GFP-expressing HSV-1 recombinant virus for 48h (compared to their untreated, uninfected counterparts). These results support captopril as a therapeutic target for the treatment of HSV-1 and its associated pathologies.
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