{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T22:53:30Z","timestamp":1773788010638,"version":"3.50.1"},"reference-count":55,"publisher":"American Veterinary Medical Association (AVMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:p><jats:bold>Objective<\/jats:bold>\u2014To determine the frequency of spontaneous canine herpesvirus-1 (CHV-1) reactivation and ocular viral shedding in latently infected dogs and the effect of topical ocular administration of cyclosporine.<\/jats:p>\n<jats:p><jats:bold>Animals<\/jats:bold>\u20148 mature Beagles with experimentally induced latent CHV-1 infection.<\/jats:p>\n<jats:p><jats:bold>Procedures<\/jats:bold>\u2014Following induction of primary ocular CHV-1 infection, the presence of reactivatable CHV-1 latency was confirmed by systemically administering prednisolone to the dogs. Dogs were then monitored for 36 weeks via clinical examination and conjunctival sample CHV-1 PCR assay performed at 4-day intervals and CHV-1 virus neutralization antibody assay performed at 2-week intervals. During weeks 16 to 32, dogs were administered 0.2% cyclosporine ointment in both eyes twice daily and blood cyclosporine concentrations were monitored. During weeks 33 to 36, the presence of reactivatable CHV-1 latency was reconfirmed via systemic administration of prednisolone.<\/jats:p>\n<jats:p><jats:bold>Results<\/jats:bold>\u2014Reactivation of latent CHV-1 was not detected via clinical examination or viral shedding during the initial 32 weeks, including before and during topical ocular administration of cyclosporine, and there were no significant differences in CHV-1 virus neutralization titer increases between the study periods. Blood cyclosporine concentrations were less than assay detection limits in all dogs on the sampling days. Systemic administration of corticosteroids repeatedly resulted in ocular disease and viral shedding.<\/jats:p>\n<jats:p><jats:bold>Conclusions and Clinical Relevance<\/jats:bold>\u2014Spontaneous CHV-1 reactivation did not occur frequently in latently infected mature dogs, and this was not altered by topical ocular administration of cyclosporine. This characteristic may be a factor contributing to the lower frequency of recurrent herpetic ocular disease in dogs relative to other host species and their associated alphaherpesviruses.<\/jats:p>","DOI":"10.2460\/ajvr.73.7.1079","type":"journal-article","created":{"date-parts":[[2012,6,27]],"date-time":"2012-06-27T18:39:30Z","timestamp":1340822370000},"page":"1079-1084","source":"Crossref","is-referenced-by-count":19,"title":["Frequency of spontaneous canine herpesvirus-1 reactivation and ocular viral shedding in latently infected dogs and canine herpesvirus-1 reactivation and ocular viral shedding induced by topical administration of cyclosporine and systemic administration of corticosteroids"],"prefix":"10.2460","volume":"73","author":[{"given":"Eric C.","family":"Ledbetter","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erotides C.","family":"da 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neurons and the lymph node lymphocytes of latently infected dogs","volume":"61","author":"Miyoshi","year":"1999"},{"key":"ref3","series-title":"Theriogenology","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.theriogenology.2007.09.022","article-title":"Seroprevalence of canine herpesvirus in breeding kennels in the Gauteng Province of South Africa","volume":"69","author":"N\u00f6thling","year":"2008"},{"key":"ref4","series-title":"Vet Microbiol","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0378-1135(98)00285-5","article-title":"Prevalence of antibodies against canine herpesvirus 1 in dogs in The Netherlands in 1997\u20131998","volume":"65","author":"Rijsewijk","year":"1999"},{"key":"ref5","series-title":"Reprod Domest Anim","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1046\/j.1439-0531.2002.00363.x","article-title":"Seroprevalence of canine herpesvirus-1 in the Belgian dog population in 2000","volume":"37","author":"Ronsse","year":"2002"},{"key":"ref6","series-title":"Arch Virol","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1007\/s007050050391","article-title":"A serological study of canine herpes virus-1 infection in the English dog population","volume":"143","author":"Reading","year":"1998"},{"key":"ref7","series-title":"Vet Microbiol","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/S0378-1135(96)01227-8","article-title":"Detection of canine herpesvirus 1 in a wide range of tissues using the polymerase chain reaction","volume":"53","author":"Burr","year":"1996"},{"key":"ref8","series-title":"Res Vet Sci","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.rvsc.2010.10.016","article-title":"Seroprevalence of canine herpesvirus-1 in Turkish dog population","volume":"92","author":"Yesilba","year":"2012"},{"key":"ref9","series-title":"J Am Vet Med Assoc","doi-asserted-by":"publisher","first-page":"954","DOI":"10.2460\/javma.235.8.954","article-title":"Virologic survey of dogs with naturally acquired idiopathic conjunctivitis","volume":"235","author":"Ledbetter","year":"2009"},{"key":"ref10","series-title":"Vet Ophthalmol","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1111\/j.1463-5224.2009.00709.x","article-title":"Outbreak of ocular disease associated with naturally-acquired canine herpesvirus-1 infection in a closed domestic dog colony","volume":"12","author":"Ledbetter","year":"2009"},{"key":"ref11","series-title":"J Vet Intern Med","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1111\/j.1939-1676.2010.0512.x","article-title":"Disseminated canine herpesvirus-1 infection in an immunocompromised adult dog","volume":"24","author":"Malone","year":"2010"},{"key":"ref12","series-title":"J Clin Microbiol","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1128\/JCM.02128-09","article-title":"Nosocomial outbreak of serious canine infectious tracheobronchitis (kennel cough) caused by canine herpesvirus infection","volume":"48","author":"Kawakami","year":"2010"},{"key":"ref13","series-title":"Vet Microbiol","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.vetmic.2009.03.013","article-title":"Experimental reactivation of latent canine herpesvirus-1 and induction of recurrent ocular disease in adult dogs","volume":"138","author":"Ledbetter","year":"2009"},{"key":"ref14","series-title":"Cornell Vet","first-page":"291","article-title":"Repeated canine herpesvirus (CHV) reactivation in dogs by an immunosuppressive drug","volume":"83","author":"Okuda","year":"1993"},{"key":"ref15","series-title":"Am J Vet Res","first-page":"551","article-title":"Virus reactivation in bitches with a medical history of herpesvirus infection","volume":"54","author":"Okuda","year":"1993"},{"key":"ref16","series-title":"J Am Vet Med Assoc","doi-asserted-by":"publisher","first-page":"376","DOI":"10.2460\/javma.229.3.376","article-title":"Corneal ulceration associated with naturally occurring canine herpesvirus-1 infection in two adult dogs","volume":"229","author":"Ledbetter","year":"2006"},{"key":"ref17","series-title":"Exp Eye Res","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1016\/j.exer.2010.03.001","article-title":"The effect of topical ocular corticosteroid administration in dogs with experimentally induced latent canine herpesvirus-1 infection","volume":"90","author":"Ledbetter","year":"2010"},{"key":"ref18","series-title":"Vet Rec","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1136\/vr.100.7.128","article-title":"Experimental induction of feline viral rhinotracheitis virus re-excretion in FVR-recovered cats","volume":"100","author":"Gaskell","year":"1977"},{"key":"ref19","series-title":"Invest Ophthalmol Vis Sci","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1167\/iovs.04-0614","article-title":"HSV-1 DNA in tears and saliva of normal adults","volume":"46","author":"Kaufman","year":"2005"},{"key":"ref20","series-title":"J Infect Dis","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1086\/591913","article-title":"Rapidly cleared episodes of herpes simplex virus reactivation in immunocompetent adults","volume":"198","author":"Mark","year":"2008"},{"key":"ref21","series-title":"Am J Vet Res","first-page":"338","article-title":"Use of nested polymerase chain reaction to identify feline herpesvirus in ocular tissue from clinically normal cats and cats with corneal sequestra or conjunctivitis","volume":"58","author":"Stiles","year":"1997"},{"key":"ref22","series-title":"Adv Pharmacol","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/S1054-3589(08)60276-8","article-title":"In vivo pharmacological effects of ciclosporin and some analogues","volume":"35","author":"Borel","year":"1996"},{"key":"ref23","series-title":"Vet Rec","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1136\/vr.144.25.696","article-title":"Comparison of cyclosporin A and dexamethasone in the treatment of canine nictitans plasmacytic conjunctivitis","volume":"144","author":"Gonzalez Alonso-Alegre","year":"1999"},{"key":"ref24","series-title":"Eye (Lond)","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/eye.1997.126","article-title":"A comparative approach to topical cyclosporine therapy","volume":"11","author":"Williams","year":"1997"},{"key":"ref25","series-title":"J Am Vet Med Assoc","first-page":"1043","article-title":"Topical administration of cyclosporine for treatment of keratoconjunctivitis sicca in dogs","volume":"199","author":"Morgan","year":"1991"},{"key":"ref26","series-title":"Vet Rec","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1136\/vr.137.20.504","article-title":"Treatment of keratoconjunctivitis sicca in dogs with cyclosporine ophthalmic ointment: a European clinical field trial","volume":"137","author":"Sansom","year":"1995"},{"key":"ref27","series-title":"J Small Anim Pract","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1111\/j.1748-5827.1995.tb02821.x","article-title":"Treatment of canine nictitans plasmacytic conjunctivitis with 0.2 per cent cyclosporin ointment","volume":"36","author":"Read","year":"1995"},{"key":"ref28","series-title":"Vet Rec","first-page":"635","article-title":"Comparison of topical cyclosporin and dexamethasone for the treatment of chronic superficial keratitis in dogs","volume":"137","author":"Williams","year":"1995"},{"key":"ref29","series-title":"J Am Vet Med Assoc","first-page":"1039","article-title":"Clinical evaluation of 1% cyclosporine for topical treatment of keratoconjunctivitis sicca in dogs","volume":"199","author":"Olivero","year":"1991"},{"key":"ref30","series-title":"Adv Exp Med Biol","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1007\/978-1-4615-5359-5_144","article-title":"Cyclosporine distribution into the conjunctiva, cornea, lacrimal gland, and systemic blood following topical dosing of cyclosporine to rabbit, dog, and human eyes","volume":"438","author":"Acheampong","year":"1998"},{"key":"ref31","series-title":"Curr Eye Res","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1076\/ceyr.18.2.91.5381","article-title":"Distribution of cyclosporin A in ocular tissues after topical administration to albino rabbits and Beagle dogs","volume":"18","author":"Acheampong","year":"1999"},{"key":"ref32","series-title":"Vet Immunol Immunopathol","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/0165-2427(95)05471-5","article-title":"Cellular immunity in dogs with keratoconjunctivitis sicca before and after treatment with topical 2% cyclosporine","volume":"49","author":"Gilger","year":"1995"},{"key":"ref33","series-title":"Curr Opin Immunol","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.coi.2004.05.003","article-title":"Immune control of herpes simplex virus during latency","volume":"16","author":"Khanna","year":"2004"},{"key":"ref34","series-title":"J Virol","doi-asserted-by":"publisher","first-page":"11178","DOI":"10.1128\/JVI.75.22.11178-11184.2001","article-title":"Gamma interferon can prevent herpes simplex virus type 1 reactivation from latency in sensory neurons","volume":"75","author":"Liu","year":"2001"},{"key":"ref35","series-title":"J Exp Med","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1084\/jem.191.9.1459","article-title":"CD8(+) T cells can block herpes simplex virus type 1 (HSV-1) reactivation from latency in sensory neurons","volume":"191","author":"Liu","year":"2000"},{"key":"ref36","series-title":"J Neuroimmunol","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/0165-5728(95)00068-D","article-title":"Immune cell infiltration and persistence in the mouse trigeminal ganglion after infection of the cornea with herpes simplex virus type 1","volume":"61","author":"Shimeld","year":"1995"},{"key":"ref37","series-title":"Am J Vet Res","doi-asserted-by":"publisher","first-page":"513","DOI":"10.2460\/ajvr.70.4.513","article-title":"Experimental primary ocular canine herpesvirus-1 infection in adult dogs","volume":"70","author":"Ledbetter","year":"2009"},{"key":"ref38","series-title":"Vet Res","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1051\/vetres:2006063","article-title":"Feline herpesvirus","volume":"38","author":"Gaskell","year":"2007"},{"key":"ref39","series-title":"Prog Retin Eye Res","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/j.preteyeres.2006.05.001","article-title":"Herpes simplex keratitis","volume":"25","author":"Kaye","year":"2006"},{"key":"ref40","series-title":"Arch Ophthalmol","first-page":"1617","article-title":"Psychological stress and other potential triggers for recurrences of herpes simplex virus eye infections","volume":"118","year":"2000"},{"key":"ref41","series-title":"J Virol","doi-asserted-by":"publisher","first-page":"11069","DOI":"10.1128\/JVI.00243-07","article-title":"Spontaneous reactivation of herpes simplex virus type 1 in latently infected murine sensory ganglia","volume":"81","author":"Margolis","year":"2007"},{"key":"ref42","series-title":"Proc Natl Acad Sci U S A","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1073\/pnas.022301899","article-title":"Spontaneous molecular reactivation of herpes simplex virus type 1 latency in mice","volume":"99","author":"Feldman","year":"2002"},{"key":"ref43","series-title":"Sex Transm Infect","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1136\/sti.2006.022020","article-title":"Longitudinal study of herpes simplex virus type 2 infection using viral dynamic modelling","volume":"83","author":"Crespi","year":"2007"},{"key":"ref44","series-title":"J Exp Med","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1084\/jem.20061792","article-title":"Virus-specific CD8+ T cells accumulate near sensory nerve endings in genital skin during subclinical HSV-2 reactivation","volume":"204","author":"Zhu","year":"2007"},{"key":"ref45","series-title":"Vet Ophthalmol","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1111\/j.1463-5224.2010.00818.x","article-title":"Lack of effects on lymphocyte function from chronic topical ocular cyclosporine medication: a prospective study","volume":"13","author":"Williams","year":"2010"},{"key":"ref46","series-title":"Aust N Z J Ophthalmol","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1111\/j.1442-9071.1995.tb00186.x","article-title":"Persisting epithelial herpes simplex keratitis while on cyclosporin-A ointment","volume":"23","author":"Field","year":"1995"},{"key":"ref47","series-title":"Invest Ophthalmol Vis Sci","first-page":"1170","article-title":"Effects of cyclosporine A on clinical and immunological parameters in herpes simplex keratitis","volume":"28","author":"Meyers-Elliott","year":"1987"},{"key":"ref48","series-title":"Exp Eye Res","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/S0014-4835(87)80151-3","article-title":"Effect of cyclosporine A on the corneal inflammatory response in herpes simplex virus keratitis","volume":"45","author":"Meyers-Elliott","year":"1987"},{"key":"ref49","series-title":"J Heart Transplant","first-page":"390","article-title":"Infection as a complication of heart transplantation","volume":"7","author":"Linder","year":"1988"},{"key":"ref50","series-title":"Transplant Proc","doi-asserted-by":"publisher","first-page":"2118","DOI":"10.1016\/j.transproceed.2004.08.008","article-title":"Viral infection following kidney transplantation: long-term follow-up in a single center","volume":"36","author":"Hwang","year":"2004"},{"key":"ref51","series-title":"Br J Ophthalmol","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1136\/bjo.82.4.423","article-title":"Ocular complications of heart, lung, and liver transplantation","volume":"82","author":"Ng","year":"1998"},{"key":"ref52","series-title":"Vet J","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/j.tvjl.2006.01.014","article-title":"Brain abscess in a dog immunosuppressed using cyclosporin","volume":"173","author":"Smith","year":"2007"},{"key":"ref53","series-title":"J Am Anim Hosp Assoc","doi-asserted-by":"publisher","first-page":"198","DOI":"10.5326\/0410198","article-title":"Cutaneous manifestations of disseminated toxoplasmosis in an immunosuppressed dog","volume":"41","author":"Webb","year":"2005"},{"key":"ref54","series-title":"Vet Clin Pathol","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1111\/j.1939-165X.2010.00247.x","article-title":"Disseminated nocardiosis caused by Nocardia abscessus in a dog","volume":"39","author":"MacNeill","year":"2010"},{"key":"ref55","series-title":"Aust Vet J","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1111\/j.1751-0813.2006.00068.x","article-title":"Successful treatment of disseminated cutaneous phaeohyphomycosis in a dog","volume":"84","author":"Swift","year":"2006"}],"container-title":["American Journal of Veterinary 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