The significance of the arginine and arginase of tears in experimentally-induced herpes simplex corneae

Kahán, I.L.; Hajas, Katalin; Halász, A

doi:10.1007/bf00414614

Cited by 11 publications

(13 citation statements)

References 16 publications

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“…In addition, arginase 1 metabolism appeared to increase 10 fold in a murine model of HSV-1 induced stromal keratitis infection, 12 suggesting a correlation with symptom resolution and arginine levels. Kahan et al also found that corneal herpes was accompanied by the accumulation of arginine in the corneal epithelium, a potential finding which they attributed to increased viral replication and virulence 13 . Furthermore, the addition of topical ocular arginase led to a resolution of the herpetic episode, further substantiating arginine's role in infection and disease progression 13 …”

Section: Discussionmentioning

confidence: 97%

“…Kahan et al also found that corneal herpes was accompanied by the accumulation of arginine in the corneal epithelium, a potential finding which they attributed to increased viral replication and virulence 13 . Furthermore, the addition of topical ocular arginase led to a resolution of the herpetic episode, further substantiating arginine's role in infection and disease progression 13 …”

Section: Discussionmentioning

confidence: 97%

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Recurrent herpes zoster ophthalmicus in a young, healthy individual taking high doses of l-Arginine

LoBue¹,

Tailor

Carlson

et al. 2019

American Journal of Ophthalmology Case Reports

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Purpose To report a case of a healthy, young male with recurrent herpes zoster ophthalmicus (HZO) and high-dose l -arginine supplementation. Observations A 39-year-old man presented to another institution with a HZO involving the right eye. He was treated with oral acyclovir with complete resolution. Four months later the patient had a recurrent HZO episode and was started again on oral acyclovir. After resolution of the episode, the patient was continued on 1 g of oral acyclovir daily as a prophylactic measure. He then presented to our institution for a second opinion. The patient was otherwise healthy, with no past medical history involving systemic immunosuppressant agents or HIV. However, the patient was an active weight lifter taking high doses of amino acids. A diet recall was performed prior to both HZO episodes, which calculated an average intake of 46.5 g of l -arginine a day. Examination revealed 20/40 best-corrected acuity, anterior stromal haze in the visual axis, and inferior superficial punctate keratitis in the right eye. The patient was treated for dry eye disease with punctual plugs and artificial tears. The patient was instructed to decrease all supplemental arginine consumption while continuing with oral acyclovir prophylaxis for one year. Conclusions and importance l -arginine is associated with the replication and virulence of a variety of viruses in vitro, including herpes simplex and varicella zoster. Although arginine consumption increased prior to the initial and recurrent HZO infection, further investigation needs to be performed to deem if a true association exists.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

Recurrent herpes zoster ophthalmicus in a young, healthy individual taking high doses of l-Arginine

LoBue¹,

Tailor

Carlson

et al. 2019

American Journal of Ophthalmology Case Reports

View full text Add to dashboard Cite

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“…It has been hypothesized that the eye maintains its immunoprivilege and avascularity by keeping arginine at low levels (Fu et al, 2011). During HSV infection of the eye, disease progression correlates with increased arginine levels (Kahan et al, 1979). In this regard, peg-ArgI has potential to modulate these deleterious disease-associated sequelae.…”

Section: Discussionmentioning

confidence: 99%

Development and evaluation of a host-targeted antiviral that abrogates herpes simplex virus replication through modulation of arginine-associated metabolic pathways

2016

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Since their inception five decades ago, most antivirals have been engineered to disrupt a single viral protein or process that is essential for viral replication. This approach has limited the overall therapeutic effectiveness and applicability of current antivirals due to restricted viral specificity, a propensity for development of drug resistance, and an inability to control deleterious host-mediated inflammation. As obligate intracellular parasites, viruses are reliant on host metabolism and macromolecular synthesis pathways. Of these biosynthetic processes, many viruses, including Herpes simplex viruses (HSV), are absolutely dependent on the bioavailability of arginine, a non-essential amino acid that is critical for many physiological and pathophysiological processes associated with either facilitating viral replication or progression of disease. To assess if targeting host arginine-associated metabolic pathways would inhibit HSV replication, a pegylated recombinant human Arginase I (peg-ArgI) was generated and its in vitro anti-herpetic activity was evaluated. Cells continuously treated with peg-ArgI for over 48 hours exhibited no signs of cytotoxicity or loss of cell viability. The antiviral activity of peg-ArgI displayed a classical dose-response curve with IC50’s in the sub-nanomolar range. peg-ArgI potently inhibited HSV-1 and HSV-2 viral replication, infectious virus production, cell-to-cell spread/transmission and virus-mediated cytopathic effects. Not unexpectedly given its host-targeted mechanism of action, peg-ArgI showed similar effectiveness at controlling replication of single and multidrug resistant HSV-1 mutants. These findings illustrate that targeting host arginine-associated metabolic pathways is an effective means of controlling viral replicative processes. Further exploration into the breadth of viruses inhibited by peg-ArgI, as well as the ability of peg-ArgI to suppress arginine-associated virus-mediated pathophysiological disease processes is warranted.

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“…Experiments show that herpes does not grow without Arg [53] , [54] , [55] , as Arg is a key building block of the viral envelope that facilitates localization, fusion, and entrance to host cell nuclei [56] , [57] . Arg also seems to promote herpes-associated corneal tumors [58] and was highly concentrated in tears of rabbits with corneal herpes [59] . This is particularly relevant, as 93% of Hawaiian green turtles with FP have ocular tumors [60] ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Land Use, Macroalgae, and a Tumor-Forming Disease in Marine Turtles

2010

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Wildlife diseases are an increasing concern for endangered species conservation, but their occurrence, causes, and human influences are often unknown. We analyzed 3,939 records of stranded Hawaiian green sea turtles (Chelonia mydas) over 28 years to understand fibropapillomatosis, a tumor-forming disease linked to a herpesvirus. Turtle size is a consistent risk factor and size-standardized models revealed considerable spatial and temporal variability. The disease peaked in some areas in the 1990s, in some regions rates remained constant, and elsewhere rates increased. Land use, onshore of where the turtles feed, may play a role. Elevated disease rates were clustered in watersheds with high nitrogen-footprints; an index of natural and anthropogenic factors that affect coastal eutrophication. Further analysis shows strong epidemiological links between disease rates, nitrogen-footprints, and invasive macroalgae and points to foraging ecology. These turtles now forage on invasive macroalgae, which can dominate nutrient rich waters and sequester environmental N in the amino acid arginine. Arginine is known to regulate immune activity, promote herpesviruses, and contribute to tumor formation. Our results have implications for understanding diseases in aquatic organisms, eutrophication, herpesviruses, and tumor formation.

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The significance of the arginine and arginase of tears in experimentally-induced herpes simplex corneae

Cited by 11 publications

References 16 publications

Recurrent herpes zoster ophthalmicus in a young, healthy individual taking high doses of l-Arginine

Recurrent herpes zoster ophthalmicus in a young, healthy individual taking high doses of l-Arginine

Development and evaluation of a host-targeted antiviral that abrogates herpes simplex virus replication through modulation of arginine-associated metabolic pathways

Land Use, Macroalgae, and a Tumor-Forming Disease in Marine Turtles

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