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. Author manuscript; available in PMC: 2017 Aug 1.
Published in final edited form as: Antiviral Res. 2016 May 15;132:13–25. doi: 10.1016/j.antiviral.2016.05.009

Figure 3.

Figure 3

peg-ArgI depletion of arginine potently inhibits infectious HSV-1 viral yield and suppresses HSV-mediated cytopathic effects across a range of multiplicity of infections. (A) Vero cells were infected at a multiplicity of infection (MOI) of 0.1, 1.0 or 5.0 and were subsequently treated with either peg-ArgI (5µg/ml; red) or varying doses of acyclovir (shades of blue). The total HSV-1 infectious viral yield was determined at 24h post-infection by titering lysed cell stocks on Vero cells. Each bar represents the mean +/− the S.E.M. of six replicates. Experiments were repeated at least 3 times. One way analysis of variance (ANOVA) with Kruskal-Wallis post-test was utilized to analyze differences between all treatment groups. Asterisks indicate significant differences between the indicated treatments: *** p<0.0001; ** p<0.001; * p<0.01. The limit of detection for these assays was 50 plaque forming units/ml. (B) peg-ArgI treatment suppresses HSV-mediated cytopathic effects. Vero cells were infected with HSV-1(McKrae) at an MOI of 0.1, 1.0 or 5.0 and subsequently treated with peg-ArgI (1.25µg/ml) or acyclovir (10 or 150µM). The extent of HSV-mediated cytopathic effects were visualized by phase-contrast microscopy at 24h post-infection and digitally photographed. (C) Increased ornithine levels are not responsible for the anti-herpetic effects associated with peg-ArgI mediated conversion of arginine to ornithine. Addition of 2mM ornithine to either normal media (gray bars) or to media treated with peg-ArgI (red bars) did not inhibit replication of HSV-1. (D) Increasing concentrations of arginine above the 400µM baseline results in concomitant increases in infectious HSV-1 viral yield (D; red). Treatment of infected cells with control peg- BSA does not affect viral yields across all doses relative to mock treatments (D; blue). (E) peg- ArgI treatment nullifies the additive replicative effects of increasing arginine concentrations (E; red); thereby, increasing the fold reduction in HSV-1 viral yield relative to mock treatments (E; blue).