AJVR, Vol 64, No. 1, January 2003 37 D espite routine vaccination of many cats, the advent of antiviral drugs with efficacy against feline her- pesvirus type 1 (FHV-1), and the environmental insta- bility of this virus, FHV-1 remains a common pathogen of cats throughout the world. 1 The most likely reason for this is the virus’ ability to establish lifelong neural latency interspersed with episodes of viral reactivation. It is estimated that 80% of cats become latently infected following primary exposure to FHV-1. Of the latently infected cats, approximately 50% shed virus at some stage during their lives, and 29% do so without a rec- ognized stimulus. 2 Many latently infected cats shed virus without clinical evidence of disease. This subpop- ulation of cats represents an epidemiologically critical reservoir of virus that ensures perpetuation of infection and disease in the general feline population. This is of particular relevance in breeding and boarding catteries, research colonies, animal shelters, and multicat house- holds. Currently, no treatment has been identified that reduces FHV-1 shedding by latently infected cats. The amino acid L-lysine has received attention for treatment of human beings latently infected with her- pes simplex virus type 1 (HSV-1), another alphaher- pesvirus with similar biological behavior to FHV-1. L- Lysine has been demonstrated to reduce the in vitro replication of HSV-1. The presumed mechanism is antagonism of the growth-promoting effect of arginine, which is an essential amino acid for HSV-1 replica- tion. 3,4 Results of clinical trials in humans suffering recurrent HSV-1-related lesions indicate that patients taking L-lysine orally experienced a reduction in lesion recurrence rate, severity, and healing time. However, in some of these trials, patients were required to limit their arginine intake. 5-7 Recently, we demonstrated that in vitro replication of FHV-1 is suppressed by approximately 80% when the L-lysine concentration in the culture medium is doubled. 8 This effect was negated at higher arginine concentrations suggesting a similar mechanism of argi- nine antagonism to that described for HSV-1. Because cats are exquisitely sensitive to arginine deficiency, 9 the practicality of oral lysine supplementation, with or without coincident arginine restriction for manage- ment of FHV-1 infections, requires careful investiga- tion. Stiles et al 10 recently demonstrated the efficacy of oral administration of lysine to cats prior to primary exposure to FHV-1. Cats receiving 500 mg of L-lysine every 12 hours orally beginning 6 hours prior to exper- imental primary inoculation with FHV-1, had less severe conjunctivitis, compared with cats receiving placebo. However, viral shedding, as determined by virus isolation (VI), did not differ between groups. No ill effects attributable to lysine administration were observed. The study reported here was designed to examine the effect of orally administered L-lysine on clinical signs of FHV-1 infection and spontaneous and reactivated shedding of FHV-1 in latently infected cats. Received May 6, 2002. Accepted August 19, 2002. From the Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211 (Maggs, Nasisse) and the Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616 (Kass). Dr. Maggs’ present address is the Department of Surgical and Radiological Sciences, 2112 Tupper Hall, School of Veterinary Medicine, University of California, Davis, CA 95616. Dr. Nasisse’s present address is Carolina Veterinary Specialists, 501 Nicholas Rd, Greensboro, NC 27409. Supported in part by a grant from the Winn Feline Foundation. Presented in part at the 28th Annual Meeting of the American College of Veterinary Ophthalmologists, Santa Fe, New Mexico, November, 1997. Address correspondence to Dr. Maggs. Efficacy of oral supplementation with L-lysine in cats latently infected with feline herpesvirus David J. Maggs, BVSc; Mark P. Nasisse, DVM; Philip H. Kass, DVM, PhD Objective—To examine the effects of orally adminis- tered L-lysine on clinical signs of feline herpesvirus type 1 (FHV-1) infection and ocular shedding of FHV-1 in latently infected cats. Animals—14 young adult, FHV-1-naive cats. Procedure—Five months after primary conjunctival inoculation with FHV-1, cats were rehoused and assigned to receive 400 mg of L-lysine in food once daily for 30 days or food only. On day 15, all cats received methylprednisolone to induce viral reactiva- tion. Clinical signs of infection were graded, and viral shedding was assessed by a polymerase chain reac- tion assay throughout our study. Peak and trough plas- ma amino acid concentrations were assessed on day 30. Results—Fewer cats and eyes were affected by con- junctivitis, and onset of clinical signs of infection was delayed on average by 7 days in cats receiving L-lysine, compared with cats in the control group; however, significant differences between groups were not demonstrated. Significantly fewer viral shedding episodes were identified in the treatment group cats, compared with the control group cats, after rehousing but not following corticosteroid- induced viral reactivation. Mean plasma L-lysine con- centration was significantly increased at 3 hours but not at 24 hours after L-lysine administration. Plasma arginine concentration was not significantly altered. Conclusions and Clinical Relevance—Once daily oral administration of 400 mg of L-lysine to cats latent- ly infected with FHV-1 was associated with reduced viral shedding following changes in housing and hus- bandry but not following corticosteroid administration. This dose caused a significant but short-term increase in plasma L-lysine concentration without altering plas- ma arginine concentration or inducing adverse clinical effects. (Am J Vet Res 2003;64:37–42)