FELINE HERPESVIRUS INFECTION IN FOUR CAPTIVE CHEETAHS (ACINONYX JUBATUS) POSTVACCINATION.

Cheetahs (Acinonyx jubatus) are particularly susceptible to feline herpesvirus-1 (FHV-1). Recommendations for preventive health care in cheetahs include vaccination against FHV-1 using killed and modified live virus (MLV) vaccines. Although MLV vaccines tend to induce a more robust immune response than killed vaccines, they can induce disease. This case series details an FHV-1 outbreak in four adult cheetahs following the use of MLV vaccine in one of them. All four cheetahs developed severe FHV-1 clinical signs and were euthanized. Clinical signs included depression, anorexia, nasal discharge, ocular discharge, sneezing, and ulcerative dermatitis. Herpesvirus infection was diagnosed using history, clinical signs, polymerase chain reaction, and histologic evaluation. The timeline of events suggests the MLV vaccine was the inciting cause, although this was not conclusively proven. Outcome of this case suggests that when considering MLV vaccines for cheetahs, careful risk and benefit discussions are merited.

Antiviral effect of sinefungin on in vitro growth of feline herpesvirus type 1.

Feline herpesvirus type 1 (FHV-1) causes a potentially fatal disease in cats. Through the use of virus inhibition and cytotoxicity assays, sinefungin, a nucleoside antibiotic, was assessed for its potential to inhibit the growth of FHV-1. Sinefungin inhibited in vitro growth of FHV-1 most significantly over other animal viruses, such as feline infectious peritonitis virus, equine herpesvirus, pseudorabies virus and feline calicivirus. Our results revealed that sinefungin specifically suppressed the replication of FHV-1 after its adsorption to the host feline kidney cells in a dose-dependent manner without obvious cytotoxicity to the host cells. This antibiotic can potentially offer a highly effective treatment for animals infected with FHV-1, providing alternative medication to currently available antiviral therapies.

Antiviral activity of PHA767491 on Caprine alphaherpesvirus 1 in vitro.

Caprine alphaherpesvirus 1 (CpHV-1) induces genital lesions in its natural host similar to those caused by Human alphaherpesvirus 2 (HHV-2), commonly named herpes simplex virus 2 (HSV-2) in human patients. CpHV-1 infection in goats could represent a useful homologous animal model for the study of HSV-2 infection, chiefly for the assessment of antiviral drugs in in vivo studies. PHA767491 is a potent inhibitor of HSV-1 and HSV-2, being able to limit replication of HHVs both in vitro and in the mouse model. In the present study the antiviral efficacy of PHA767491 against CpHV-1 was evaluated in vitro in MDBK cells. PHA767491 inhibited significantly CpHV-1 replication in a dose-dependent fashion by up to 2.50 log10 TCID50/50 µl and was able to decrease viral DNA by nearly 8 log10. These findings confirm that PHA767491 is highly effective not only against simplexviruses (HSV-1 and HSV-2), but also against the varicellovirus CpHV-1. Experiments will be necessary to assess whether PHA767491 is suitable for treatment of vaginal lesions in CpHV-1-goat model. This could provide hints for the therapy of genital alphaherpesvirus infections in humans.

Cat flu: Broad spectrum polymeric antivirals.

Feline herpesvirus type 1 (FHV-1) and feline calicivirus (FCV) are considered as main causes of feline upper respiratory tract disease and the most common clinical manifestations include rhinotracheitis, conjunctivitis, and nasal/facial ulcerations. While the primary infection is relatively mild, secondary infections pose a threat to young or immunocompromised cats and may result in a fatal outcome. In this study, we made an effort to evaluate antiviral potency of poly(sodium 4-styrenesulfonates) (PSSNa) as potent FHV-1 and FCV inhibitors for topical use. Mechanistic studies showed that PSSNa exhibits a different mechanism of action depending on target species. While PSSNa acts directly on FHV-1 particles blocking their interaction with the host's cell and preventing the infection, the antiviral potency against FCV is based on inhibition at late stages of the viral replication cycle. Altogether, PSSNa polymers are promising drug candidates to be used in the treatment and prevention of the viral upper respiratory tract disease (URTD), regardless of the cause.

Virucidal activity of ginger essential oil against caprine alphaherpesvirus-1.

The emergence of alphaherpesvirus strains resistant to commonly used antiviral drugs has prompted the research for alternative, biologically active anti-herpetic agents. Essential oils (EOs) have shown anti-infective properties against human herpes simplex viruses (HSV-1 and -2). Caprine alphaherpesvirus 1 (CpHV-1) induces genital lesions in its natural host and it is regarded as a useful homologous animal model for the study of HSV-2 infection, chiefly for the assessment of antiviral drugs in in vivo studies. In the present study we evaluated the activity in vitro of ginger EO (GEO) against CpHV-1. GEO was found to be effective as virucide on cell-free virus, inactivating CpHV-1 up to 100%. The virucidal activity of GEO is likely accounted for by disruption of herpesvirus envelope and its associated structures which are necessary for virus adsorption and entry into host cells. On the opposite, GEO was not able to inhibit virus adsorption and/or replication, as treatment of cells before and after infection did not abolish virus infectivity. GEO could be suggested for topical applications in in vivo experiments using CpHV-1/goat model, since the lipophilic nature of EOs favours their adsorption through the cutaneous/mucosal barrier, either alone or in conjunction with other molecules. These findings open several perspectives in terms of therapeutic possibilities for a number of human and animal alphaherpesviruses.

Intensive Distribution of G2-Quaduplexes in the Pseudorabies Virus Genome and Their Sensitivity to Cations and G-Quadruplex Ligands.

Guanine-rich sequences in the genomes of herpesviruses can fold into G-quadruplexes. Compared with the widely-studied G3-quadruplexes, the dynamic G2-quadruplexes are more sensitive to the cell microenvironment, but they attract less attention. Pseudorabies virus (PRV) is the model species for the study of the latency and reactivation of herpesvirus in the nervous system. A total of 1722 G2-PQSs and 205 G3-PQSs without overlap were identified in the PRV genome. Twelve G2-PQSs from the CDS region exhibited high conservation in the genomes of the Varicellovirus genus. Eleven G2-PQSs were 100% conserved in the repeated region of the annotated PRV genomes. There were 212 non-redundant G2-PQSs in the 3' UTR and 19 non-redundant G2-PQSs in the 5' UTR, which would mediate gene expression in the post-transcription and translation processes. The majority of examined G2-PQSs formed parallel structures and exhibited different sensitivities to cations and small molecules in vitro. Two G2-PQSs, respectively, from 3' UTR of UL5 (encoding helicase motif) and UL9 (encoding sequence-specific ori-binding protein) exhibited diverse regulatory activities with/without specific ligands in vivo. The G-quadruplex ligand, NMM, exhibited a potential for reducing the virulence of the PRV Ea strain. The systematic analysis of the distribution of G2-PQSs in the PRV genomes could guide further studies of the G-quadruplexes' functions in the life cycle of herpesviruses.

The HIV Integrase Inhibitor Raltegravir Inhibits Felid Alphaherpesvirus 1 Replication by Targeting both DNA Replication and Late Gene Expression.

Alphaherpesvirus-associated ocular infections in humans caused by human alphaherpesvirus 1 (HHV-1) remain challenging to treat due to the frequency of drug application required and the potential for the selection of drug-resistant viruses. Repurposing on-the-market drugs is a viable strategy to accelerate the pace of drug development. It has been reported that the human immunodeficiency virus (HIV) integrase inhibitor raltegravir inhibits HHV-1 replication by targeting the DNA polymerase accessory factor and limits terminase-mediated genome cleavage of human betaherpesvirus 5 (HHV-5). We have previously shown, both in vitro and in vivo, that raltegravir can also inhibit the replication of felid alphaherpesvirus 1 (FeHV-1), a common ocular pathogen of cats with a pathogenesis similar to that of HHV-1 ocular disease. In contrast to what was reported for HHV-1, we were unable to select for a raltegravir-resistant FeHV-1 strain in order to define any basis for drug action. A candidate-based approach to explore the mode of action of raltegravir against FeHV-1 showed that raltegravir did not impact FeHV-1 terminase function, as described for HHV-5. Instead, raltegravir inhibited DNA replication, similarly to HHV-1, but by targeting the initiation of viral DNA replication rather than elongation. In addition, we found that raltegravir specifically repressed late gene expression independently of DNA replication, and both activities are consistent with inhibition of ICP8. Taken together, these results suggest that raltegravir could be a valuable therapeutic agent against herpesviruses.IMPORTANCE The rise of drug-resistant herpesviruses is a longstanding concern, particularly among immunocompromised patients. Therefore, therapies targeting viral proteins other than the DNA polymerase that may be less likely to lead to drug-resistant viruses are urgently needed. Using FeHV-1, an alphaherpesvirus closely related to HHV-1 that similarly causes ocular herpes in its natural host, we found that the HIV integrase inhibitor raltegravir targets different stages of the virus life cycle beyond DNA replication and that it does so without developing drug resistance under the conditions tested. This shows that the drug could provide a viable strategy for the treatment of herpesvirus infections.

Transcriptome profiling of alphaherpesvirus-infected cells treated with the HIV-integrase inhibitor raltegravir reveals profound and specific alterations in host transcription.

Anti-microbial compounds typically exert their action by directly interfering with one or more stages of the pathogen's life cycle. However, some compounds also have secondary effects on the host that aid in pathogen clearance. Raltegravir is a human immunodeficiency virus (HIV)-integrase inhibitor that has been shown to alter the host immune response to HIV in addition to its direct antiviral effect. Interestingly, raltegravir can also directly inhibit the replication of various herpesviruses. However, the host-targeted effects of this drug in the context of a herpesvirus infection have not been explored. Here, we used felid alphaherpesvirus 1 (FHV-1), a close relative of human alphaherpesvirus 1 (HHV-1) that similarly causes ocular herpes, to characterize the host-targeted effects of raltegravir on corneal epithelial cells during an alphaherpesvirus infection. Using RNA deep sequencing, we found that raltegravir specifically boosts the expression of anti-angiogenic factors and promotes metabolic homeostasis in FHV-1-infected cells. In contrast, few changes in host gene transcription were found in uninfected cells. Importantly, we were able to demonstrate that these effects were specific to raltegravir and independent of the direct-acting antiviral effect of the drug, since treatment with the DNA polymerase inhibitor phosphonoacetic acid did not induce these host-targeted effects. Taken together, these results indicate that raltegravir has profound and specific effects on the host transcription profile of herpesvirus-infected cells that may contribute to the overall antiviral activity of the drug and could provide therapeutic benefits in vivo. Furthermore, this study provides a framework for future efforts evaluating the host-targeted effects of anti-microbial compounds.

Enhancement of the antiviral activity against caprine herpesvirus type 1 of Acyclovir in association with Mizoribine.

Caprine herpesvirus 1 (CpHV-1) infection in goats is responsible for genital lesions resembling the lesions induced by herpesvirus 2 in humans (HHV-2). The immunosuppressive drug Mizoribine (MIZ) is able to increase the antiviral activity of Acyclovir (ACV) against herpesvirus infections, raising interesting perspectives on new combined therapeutic strategies. In this study the anti-CpHV-1 activity in vitro of ACV alone or in combination with MIZ was evaluated. ACV (100µg/ml) displayed an antiviral effect on CpHV-1 replication. This inhibitory effect was higher when ACV (100µg/ml) was used in association with MIZ (20µg/ml). Other combinations of ACV and MIZ in various concentrations were not as effective as ACV 100µg/ml/MIZ 20µg/ml. These findings suggest that the association of ACV and MIZ is potentially useful for treatment of genital infection by herpesviruses.

A review of antiviral drugs and other compounds with activity against feline herpesvirus type 1.

Feline herpesvirus type 1 (FHV-1) is a common and important cause of ocular surface disease, dermatitis, respiratory disease, and potentially intraocular disease in cats. Many antiviral drugs developed for the treatment of humans infected with herpesviruses have been used to treat cats infected with FHV-1. Translational use of drugs in this manner ideally requires methodical investigation of their in vitro efficacy against FHV-1 followed by pharmacokinetic and safety trials in normal cats. Subsequently, placebo-controlled efficacy studies in experimentally inoculated animals should be performed followed, finally, by carefully designed and monitored clinical trials in client-owned animals. This review is intended to provide a concise overview of the available literature regarding the efficacy of antiviral drugs and other compounds with proven or putative activity against FHV-1, as well as a discussion of their safety in cats.

A novel corneal explant model system to evaluate antiviral drugs against feline herpesvirus type 1 (FHV-1).

Feline herpesvirus type-1 (FHV-1) is the most common viral cause of ocular surface disease in cats. Many antiviral drugs are used to treat FHV-1, but require frequent topical application and most lack well-controlled in vivo studies to justify their clinical use. Therefore, better validation of current and novel treatment options are urgently needed. Here, we report on the development of a feline whole corneal explant model that supports FHV-1 replication and thus can be used as a novel model system to evaluate the efficacy of antiviral drugs. The anti-herpes nucleoside analogues cidofovir and acyclovir, which are used clinically to treat ocular herpesvirus infection in cats and have previously been evaluated in traditional two-dimensional feline cell cultures in vitro, were evaluated in this explant model. Both drugs suppressed FHV-1 replication when given every 12 h, with cidofovir showing greater efficacy. In addition, the potential efficacy of the retroviral integrase inhibitor raltegravir against FHV-1 was evaluated in cell culture as well as in the explant model. Raltegravir was not toxic to feline cells or corneas, and most significantly, inhibited FHV-1 replication at 500 µM in both systems. Importantly, this drug was effective when given only once every 24 h. Taken together, our data indicate that the feline whole corneal explant model is a useful tool for the evaluation of antiviral drugs and, furthermore, that raltegravir appears a promising novel antiviral drug to treat ocular herpesvirus infection in cats.

Impact of irradiation and immunosuppressive agents on immune system homeostasis in rhesus macaques.

In this study we examined the effects of non-myeloablative total body irradiation (TBI) in combination with immunosuppressive chemotherapy on immune homeostasis in rhesus macaques. Our results show that the administration of cyclosporin A or tacrolimus without radiotherapy did not result in lymphopenia. The addition of TBI to the regimen resulted in lymphopenia as well as alterations in the memory/naive ratio following reconstitution of lymphocyte populations. Dendritic cell (DC) numbers in whole blood were largely unaffected, while the monocyte population was altered by immunosuppressive treatment. Irradiation also resulted in increased levels of circulating cytokines and chemokines that correlated with T cell proliferative bursts and with the shift towards memory T cells. We also report that anti-thymocyte globulin (ATG) treatment and CD3 immunotoxin administration resulted in a selective and rapid depletion of naive CD4 and CD8 T cells and increased frequency of memory T cells. We also examined the impact of these treatments on reactivation of latent simian varicella virus (SVV) infection as a model of varicella zoster virus (VZV) infection of humans. None of the treatments resulted in overt SVV reactivation; however, select animals had transient increases in SVV-specific T cell responses following immunosuppression, suggestive of subclinical reactivation. Overall, we provide detailed observations into immune modulation by TBI and chemotherapeutic agents in rhesus macaques, an important research model of human disease.

In vitro inhibition of caprine herpesvirus 1 by acyclovir and mizoribine.

Caprine herpesvirus 1 (CpHV-1) infection in goats induces genital vesicular-ulcerative lesions that strictly resemble the lesions induced by herpesvirus 2 in the human host. The immunosuppressive drug Mizoribine (MIZ) was found to increase the antiviral activity of Acyclovir (ACV) against herpesvirus infections, raising interesting perspectives on new combined therapeutic strategies. In this study the anti-CpHV-1 activity in vitro of ACV alone or in combination with MIZ was characterized. When applied alone at non-toxic concentrations, ACV had a slight effect on CpHV-1 replication while in combination with MIZ a dose-dependent inhibition of the virus yield was observed with an IC50 of ACV of 28.5 µM. These findings suggest that combined therapy of ACV and MIZ is potentially exploitable in the treatment of genital infection by herpesviruses.

Clinical and antiviral effect of a single oral dose of famciclovir administered to cats at intake to a shelter.

Although famciclovir is efficacious in feline herpesvirus type 1 (FHV-1)-infected cats, effects of a single dose early in disease course have not been reported. In this two part, randomized, masked, placebo controlled study, cats received a single dose of 125 mg famciclovir (n = 43) or placebo (n = 43; pilot study), or 500 mg famciclovir (n = 41) or placebo (n = 40; clinical trial) on entering a shelter. FHV-1 PCR testing was performed, bodyweight and food intake were recorded, and signs of respiratory disease were scored prior to and 7 days following treatment. FHV-1 DNA was detected in 40% of cats in both parts at study entry. In the pilot study, ocular and nasal discharge scores increased from days 1 to 7 in famciclovir and placebo treated cats. Sneezing scores increased and bodyweight decreased in famciclovir-treated cats. The proportion of cats in which FHV-1 DNA was detected increased over time in all cats in the pilot study. In the clinical trial, food intake and median clinical disease scores for nasal discharge and sneezing increased from days 1 to 7 in both groups and demeanor scores worsened in famciclovir-treated cats. The proportion of cats shedding FHV-1 DNA was greater on day 7 than on day 1 in cats receiving 500 mg famciclovir. A single dose of famciclovir (125 or 500 mg) administered at shelter intake was not efficacious in a feline population in which 40% were already shedding FHV-1.

The processivity factor complex of feline herpes virus-1 is a new drug target.

Feline herpes virus-1 (FHV-1) is ubiquitous in the cat population and is a major cause of blindness for which antiviral drugs, including acyclovir, are not completely effective. Recurrent infections, due to reactivation of latent FHV-1 residing in the trigeminal ganglia, can lead to epithelial keratitis and stromal keratitis and eventually loss of sight. This has prompted the medical need for an antiviral drug that will specifically inhibit FHV-1 infection. A new antiviral target is the DNA polymerase and its associated processivity factor, which forms a complex that is essential for extended DNA strand synthesis. In this study we have cloned and expressed the FHV-1 DNA polymerase (f-UL30) and processivity factor (f-UL42) and demonstrated that both proteins are required to completely synthesize the 7249 nucleotide full-length DNA from the M13 primed-DNA template in vitro. Significantly, a known inhibitor of human herpes simplex virus-1 (HSV-1) processivity complex was shown to inhibit FHV-1 processive DNA synthesis in vitro and block infection of cells. This validates using f-UL42/f-UL30 as a new antiviral drug target to treat feline ocular herpes infection.

In vitro antiviral activity of Ficus carica latex against caprine herpesvirus-1.

The latex of Ficus carica Linn. (Moraceae) has been shown to possess antiviral properties against some human viruses. To determine the ability of F. carica latex (F-latex) to interfere with the infection of caprine herpesvirus-1 (CpHV-1) in vitro, F-latex was resuspended in culture media containing 1% ethanol and was tested for potential antiviral effects against CpHV-1. Titration of CpHV-1 in the presence or in the absence of F-latex was performed on monolayers of Madin Darby Bovine Kidney (MDBK) cells. Simultaneous addition of F-latex and CpHV-1 to monolayers of MDBK cells resulted in a significant reduction of CpHV-1 titres 3 days post-infection and this effect was comparable to that induced by acyclovir. The study suggests that the F-latex is able to interfere with the replication of CpHV-1 in vitro on MDBK cells and future studies will determine the mechanisms responsible for the observed antiviral activity.

Controlled release delivery of penciclovir via a silicone (MED-4750) polymer: kinetics of drug delivery and efficacy in preventing primary feline herpesvirus infection in culture.

BACKGROUND: Herpesviruses are ubiquitous pathogens that infect and cause recurrent disease in multiple animal species. Feline herpesvirus-1 (FHV-1), a member of the alphaherpesvirus family, causes respiratory illness and conjunctivitis, and approximately 80% of domestic cats are latently infected. Oral administration of famciclovir or topical application of cidofovir has been shown in masked, placebo-controlled prospective trials to reduce clinical signs and viral shedding in experimentally inoculated cats. However, to the authors' knowledge, other drugs have not been similarly assessed or were not safe or effective. Likewise, to our knowledge, no drugs have been assessed in a placebo-controlled manner in cats with recrudescent herpetic disease. Controlled-release devices would permit long-term administration of these drugs and enhance compliance. METHODS: We therefore engineered implantable cylindrical devices made from silicone (MED-4750) impregnated with penciclovir, for long-term, steady-state delivery of this drug. RESULTS: Our data show that these devices release penciclovir with a burst of drug delivery until the tenth day of release, then at an average rate of 5.063 ± 1.704 µg per day through the next 50 days with near zero-order kinetics (in comparison to MED-4750-acyclovir devices, which show the same burst kinetics and average 2.236 ± 0.625 µg/day thereafter). Furthermore, these devices suppress primary infection of FHV-1 in a cell culture system. CONCLUSIONS: The clinical deployment of these silicone-penciclovir devices may allow long-term treatment of FHV-1 infection with a single intervention that could last the life of the host cat.

Evaluation of delivery agents used for introduction of small interfering RNAs into feline corneal cells.

OBJECTIVE: To evaluate agents used for delivery of small interfering RNAs (siRNAs) into feline corneal cells, toxicity of the delivery agents, and functionality of anti-feline herpesvirus 1 (FHV-1)-specific siRNA combinations. SAMPLE: Feline primary corneal cells and 19 six-month-old colony-bred cats. PROCEDURES: siRNA delivery into corneal cells via various delivery agents was evaluated via flow cytometric detection of labeled siRNAs. Cellular toxicity was evaluated with a proliferation assay. Functionality was tested via quantitative reverse transcriptase PCR assay, plaque assay, and flow cytometry. In vivo safety was evaluated with an ocular scoring method following topical application of delivery agents containing siRNAs into eyes. Corneal biopsy specimens were used to assess safety and uptake of siRNAs into corneal cells. RESULTS: Use of 3 delivery agents resulted in > 95% transfection of primary corneal cells. Use of a peptide for ocular delivery yielded approximately 82% transfection of cells in vitro. In cultured corneal cells, use of the siRNA combinations resulted in approximately 76% to 89% reduction in FHV-1-specific mRNA, 63% to 67% reduction of FHV-1-specific proteins in treated cells, and 97% to 98% reduction in FHV-1 replication. The agents were nonirritating in eyes, caused no substantial clinical ocular signs, and were nontoxic. Histologically, corneal epithelium and stroma were normal in treated cats. However, none of the agents were effective in delivering siRNAs into the corneal cells in vivo. CONCLUSIONS AND CLINICAL RELEVANCE: The tested anti-FHV-1-specific siRNAs could potentially be used as a treatment for FHV-1 if a successful means of in vivo delivery can be achieved.

Effects of topical ocular administration of high doses of human recombinant interferon alpha-2b and feline recombinant interferon omega on naturally occurring viral keratoconjunctivitis in cats.

OBJECTIVE: To determine whether 14-day topical ocular administration of high doses of feline recombinant interferon omega (FelFN) or human recombinant interferon alpha-2b (HulFN) solution improves clinical disease and decreases virus shedding in cats with naturally acquired viral keratoconjunctivitis. ANIMALS: 36 cats with upper respiratory tract disease and ocular involvement. PROCEDURES: Cats received 1 drop of FelFN solution (1 × 10(6) U/mL), HulFN solution (1 × 10(6) U/mL), or saline (0.9% NaCl) solution (12 cats/group) in each eye twice daily for 14 days (beginning day 1). Oropharyngeal and conjunctival swab samples were collected from each cat before (day 0) and on day 14 of treatment for virus isolation (VI) and real-time quantitative PCR (RT-qPCR) testing to detect feline herpesvirus-1 and feline calicivirus. Subjective clinical scores were recorded on days 0, 3, 7, 10, and 14. RESULTS: The number of cats for which feline herpesvirus-1 was detected via VI or RT-qPCR assay was generally (albeit not always significantly) lower on day 14, compared with day 0 findings; however, findings on days 0 or 14 did not differ among groups. The number of cats for which feline calicivirus was detected via VI or RT-qPCR assay did not differ significantly between days 0 and 14 for any group. Clinical scores significantly decreased over the 14-day period but did not differ among groups. CONCLUSIONS AND CLINICAL RELEVANCE: In cats with naturally occurring viral keratoconjunctivitis, bilateral ocular administration of high doses of FelFN or HulFN twice daily for 14 days did not improve clinical disease or virus shedding, compared with treatment with saline solution.

Cidofovir does not prevent caprine herpesvirus type-1 neural latency in goats.

BACKGROUND: Cidofovir (CDV) is an acyclic nucleoside phosphonate that exhibits a potent antiviral activity against several DNA viruses. In previous studies, CDV has been shown to significantly reduce the clinical severity and the viral shedding in primary caprine herpesvirus type-1 (CpHV-1) infection in goats. CpHV-1 is an alpha-herpesvirus showing many biological similarities with human herpesvirus type-2 (HHV-2); therefore, studies conducted on the CpHV-1 goat model could provide useful information on the pathogenesis, therapy and prevention of HHV-2 infection in humans. METHODS: CDV was administered to goats infected by vaginal route with CpHV-1. Real-time PCR was carried out on sacral ganglia from CpHV-1-infected goats to detect and quantify latent CpHV-1 DNA. RESULTS: Viral DNA was variably found in all five pairs of sacral ganglia, with a more frequent involvement of the third and fourth pair. In CDV-treated goats, the amount of CpHV-1 DNA did not appear to be related either to the severity of the clinical signs or the titre of the virus shed during primary CpHV-1 infection. CONCLUSIONS: CDV failed to prevent CpHV-1 latency. Thus, vaginal CDV administration during primary herpesvirus infection, although providing immediate clinical benefits to the host might not influence the establishment of latency and, consequently, the rate of recurrent infections.