Abstract P630: Captopril Reduces Cytopathic Effects in Herpes Simplex Virus 1 (HSV-1) Infected SH-SY5Y Cells

Abstract

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.