Interleukin-17 mediates inflammatory tissue injury during orf development in goats.

Orf is an epithelial zoonotic infectious disease caused by orf virus (ORFV). Mounting studies have shown that IL-17-driven neutrophil inflammation plays a central role in inflammatory skin diseases. However, whether IL-17 plays a similar role and how does it work in the pathogenesis of orf is unclear. In this study, we found that during orf development, numerous inflammatory cells, especially neutrophils, infiltrated in the damaged lip tissue. Meanwhile, the production of IL-17 was increased in the lesion site. Further evidence showed that IL-17 potently stimulated the production of several chemokines that are crucial for neutrophil migration. In addition, IL-17 was mostly produced by CD4+ T cells and gamma delta T (γδ T) cells of the skin. In conclusion, the present study highlighted a critical role of IL-17-driven inflammation in the pathogenesis of orf and suggested that this cytokine may be a potential therapeutic target of this disease in goats.

Peste Des Petits Ruminants Virus and Goatpox Virus Co-Infection in Goats.

Infection of small ruminants with peste des petits ruminants virus (PPRV) and goatpox virus (GTPV) are endemic and can have devastating economic consequences in Asia and Africa. Co-infection with these viruses have recently been reported in goats and sheep in Nigeria. In this study, we evaluated samples from the lips of a red Sokoto goat, and describe co-infection of keratinocytes with PPRV and GTPV using histopathology and transmission electron microscopy. Eosinophilic cytoplasmic inclusion bodies were identified histologically, and ultrastructural analysis revealed numerous large cytoplasmic viral factories containing poxvirus particles and varying sizes of smaller cytoplasmic inclusions composed of PPRV nucleocapsids. These histopathological and ultrastructural findings show concurrent infection with the 2 viruses for the first time as well as the detection of PPRV particles in epithelial cells of the mucocutaneous junction of the lip.

Clinical Study on the Effectiveness of Three Products in the Treatment of Herpes Simplex Labialis.

Herpes simplex labialis (HSL) is a viral disease that affects the perioral region. No guidelines recommending an effective treatment exist. The treatment of HSL with three different products was examined. Herpatch Serum, a film-forming patch, was compared to Compeed Patches, a set of semiocclusive hydrocolloid patches, and Zovirax Cream (ingredient: 5% acyclovir). In this prospective, randomized, examiner-blind study, 180 patients with recurrent HSL were split into three groups (Compeed: n = 60, Herpatch: n = 60, Zovirax: n = 60) and examined within 24 hours of HSL outbreak (DRKS Registration No.: DRKS00007786). The primary endpoint was healing time. The secondary endpoints were the reaction rate and quality of therapy evaluated by the Clinician's Global Assessment of Therapy (CGAT) and the Subject's Global Assessment of Therapy (SGAT) (0 = no response; 10 = excellent response), respectively. There was no significant difference among the healing times for the different products. The mean (95% confidence interval) was 9.67 days (9.11-10.22) for Compeed, 9.30 days (8.75-9.85) for Herpatch, and 9.80 days (9.30-10.30) for Zovirax. The reaction rate and quality of therapy (CGAT and SGAT) of Herpatch were significantly higher than those of Compeed and Zovirax. Within the study limitations, Herpatch proved to be an effective, non-antiviral alternative in the treatment of HSL.

Herpes Simplex Virus 1 Replication, Ocular Disease, and Reactivations from Latency Are Restricted Unilaterally after Inoculation of Virus into the Lip.

Ocular herpes simplex keratitis (HSK) is a consequence of viral reactivations from trigeminal ganglia (TG) and occurs almost exclusively in the same eye in humans. In our murine oro-ocular (OO) model, herpes simplex virus 1 (HSV-1) inoculation in one side of the lip propagates virus to infect the ipsilateral TG. Replication here allows infection of the brainstem and infection of the contralateral TG. Interestingly, HSK was observed in our OO model only from the eye ipsilateral to the site of lip infection. Thus, unilateral restriction of HSV-1 may be due to differential kinetics of virus arrival in the ipsilateral versus contralateral TG. We inoculated mice with HSV-1 reporter viruses and then superinfected them to monitor changes in acute- and latent-phase gene expression in TG after superinfection compared to the control (single inoculation). Delaying superinfection by 4 days after initial right lip inoculation elicited failed superinfecting-virus gene expression and eliminated clinical signs of disease. Initial inoculation with thymidine kinase-deficient HSV-1 (TKdel) completely abolished reactivation of wild-type (WT) superinfecting virus from TG during the latent stage. In light of these seemingly failed infections, viral genome was detected in both TG. Our data demonstrate that inoculation of HSV-1 in the lip propagates virus to both TG, but with delay in reaching the TG contralateral to the side of lip infection. This delay is responsible for restricting viral replication to the ipsilateral TG, which abrogates ocular disease and viral reactivations from the contralateral side. These observations may help to understand why HSK is observed unilaterally in humans, and they provide insight into vaccine strategies to protect against HSK.IMPORTANCE Herpetic keratitis (HK) is the leading cause of blindness by an infectious agent in the developed world. This disease can occur after reactivation of herpes simplex virus 1 in the trigeminal ganglia, leading to dissemination of virus to, and infection of, the cornea. A clinical paradox is evidenced by the bilateral presence of latent viral genomes in both trigeminal ganglia, while for any given patient the disease is unilateral with recurrences in a single eye. Our study links the kinetics of early infection to unilateral disease phenomenon and demonstrates protection against viral reactivation when kinetics are exploited. Our results have direct implications in the understanding of human disease pathogenesis and immunotherapeutic strategies for the treatment of HK and viral reactivations.

Improvement of refractory acyclovir-resistant herpes simplex virus type 1 infection by continuous acyclovir administration.

Resistant herpes simplex virus type 1 (HSV-1) infection is sometimes fatal for immunocompromised patients. Here, we report 10-year-old girl receiving hematopoietic stem cell transplantation developed refractory HSV-1 infection, which was persisted to intermittent acyclovir (ACV) or foscarnet (FOS) administrations but was improved by continuous ACV administration. The isolates from the lesion were identified with low susceptibilities to ACV and FOS by plaque reduction assay due to DNA pol gene mutation. Continuous ACV administration overcomes the efficacy of intermittent administration and could be the best option to treat severe HSV-1 infectious patients.

Oral fibropapillomatosis and epidermal hyperplasia of the lip in newborn lambs associated with bovine Deltapapillomavirus.

Congenital fibropapillomatosis of the gingiva and oral mucosa and epidermal hyperplasia of the lip are described, for the first time, in two newborn lambs. Expression of the E5 oncoprotein of bovine deltapapillomavirus types 2 (BPV-2) and -13 (BPV-13) was detected in both fibropapillomas and the hyperplastic epidermal cells suggesting the BPV infection was the cause of the proliferative lesions. No DNA sequences of BPV-1 and BPV-14 were detected. Both BPV-2 and BPV-13 DNA were also amplified from peripheral blood mononuclear cells (PBMCs) of the newborn lambs' dams. The concordance between BPV genotypes detected in the blood of dam and the oral and skin pathological samples of their offspring suggests that a vertical hematogeneous transmission was most likely source of BPV infection. Immunoblotting revealed the presence of E5 dimers allowing the viral protein to be biologically active. E5 dimers bind and activate the platelet derived growth factor ß receptor (PDGFßR), a major molecular mechanism contributing to disease. The detection of E5 protein within the proliferating cells therefore adds further evidence that the BPV infection was the cause of the proliferative lesions seen in these lambs. This is the first evidence of vertical transmission of BPVs in sheep resulting in a clinical disease.

Modeling the pathology, immune responses, and kinetics of HSV-1 replication in the lip scarification model.

The lip scarification model of herpes simplex virus type 1 (HSV-1) infection can be used to study acute infection in the orofacial tissue and the establishment of viral latency. In this study, mice were inoculated with HSV-1 and tissue harvested during the acute phase of infection. Clinical presentation of classical open sores on the lip of infected mice was observed. We defined the histopathology, disease scores, and immune infiltration of the lower lip during the formation and resolution of the clinical lesions. Finally, the kinetics of virus replication and transport of viral genomes to the trigeminal ganglia were established. With the virological and pathologic events of acute infection defined, the HSV-1 lip scarification model can now be used to study primary HSV-1 infection, invasion of the trigeminal ganglia, and establishment of latency.

Herpes simplex transmission to chest and face through autoinoculation in an infant.

A 4-month-old female infant presented with a vesicular lesion on her left hand present since 1 day. A few days prior to presentation, she had a similar lesion on the lower lip. Two days after presentation, she returned with new lesions on her thorax and upper eyelid. PCR of the vesicle was positive for herpes simplex virus type 1. The transmission to her chest and face probably resulted from autoinoculation, caused by rubbing of the hand on other parts of the body. Transmission of herpes simplex through skin-to-skin contact is a common route of infection in people engaging in contact sports. Antiviral therapy was started because of the extensiveness and expansion of lesions and risk of developing herpetic keratitis. The patient completely recovered. This case shows that in an otherwise healthy infant, multiple herpetic skin lesions were not due to disseminated infection, but through autoinoculation.

Lambdapapillomavirus 2 in a Gray Wolf ( Canis lupus ) from Minnesota, USA with Oral Papillomatosis and Sarcoptic Mange.

Oral papillomatosis was diagnosed in a gray wolf ( Canis lupus ) with sarcoptic mange from Minnesota, US found dead in February 2015. Intranuclear inclusion bodies were evident histologically, and papillomaviral antigens were confirmed using immunohistochemistry. Sequencing of the L1 papillomavirus gene showed closest similarity to Lambdapapillomavirus 2.

Recent approval of Xerese in Canada: 5% acyclovir and 1% hydrocortisone topical cream in the treatment of herpes labialis.

Herpes labialis is a frequently occurring viral infection of the lips and oral mucosa. Recurring lesions are induced by viral reactivation and replication, but the symptoms leading to morbidity, such as pain and inflammation, are immune-mediated. The introduction of 5% acyclovir/1% hydrocortisone in a topical cream (Xerese™) represents a therapeutic strategy directed at both of these pathogenic processes. Applied at the onset of prodromal symptoms, this combination treatment has a good safety profile and is more effective in reducing healing time than antiviral or anti-inflammatory agents alone. Although it was US FDA-approved for herpes labialis in 2009, Xerese™ has only recently been approved for use in Canada in October 2013. Herein, we review the basic science and clinical studies that support the efficacy of this topical combination acyclovir-hydrocortisone product in treating herpes labialis and examine its safety profile, as well as touch upon other therapies that have been shown to be effective in treating this common viral condition.

Detection of genetic variations in Orf virus isolates epidemic in Xinjiang China.

Orf is an exanthemous viral disease seriously threatening the goat and sheep industry and widely epidemic in the goat and sheep populations in Xinjiang, China. In order to investigate the genetic variability of the orf virus (ORFV), three virus isolates (SHZ1, SHZ2, and SHZ3) were isolated by PCR and Vero cell culture using the clinical samples from the lips of the lambs suspected of ORFV infection. The isolates were further verified by electron microscopy and animal infection experiments. The protective antigen genes B2L, F1L, and virulence genes VIR, GIF, and VEGF in the isolates were cloned, sequenced and analyzed for genetic evolution. The results showed that B2L and F1L were relatively conservative with homology 86.7-97.9%, while VIR, GIF, particularly VEGF were considerably variable with homology 71.5-97.9% at amino acid sequence level, respectively. Phylogenetic tree analysis based on B2L and VIR showed that the isolates SHZ1 and SHZ2 were closely related with the Taiwan isolates. This is the first report to confirm that there have been genetic variations in the Xinjiang ORFV isolates. The findings provide molecular evidence about the genetic variability of the major antigenic and virulence genes in the virus isolates epidemic in Xinjiang.

Diagnosis and phylogenetic analysis of Orf virus from goats in China: a case report.

BACKGROUND: Orf virus (ORFV) is the etiological agent of contagious pustular dermatitis and is the prototype of the genus Parapoxvirus (PPV). It causes a severe exanthematous dermatitis that afflicts domestic and wild small ruminants. CASE PRESENTATION: In the present study, an outbreak of proliferative dermatitis in farmed goats. The presence of ORFV in tissue scrapings from the lips was confirmed by B2L gene polymerase chain reaction (PCR) amplification. The molecular characterization of the ORFV was performed using PCR amplification, DNA sequencing and phylogenetic analysis of the B2L gene. CONCLUSION: The results of this investigation indicated that the outbreak was caused by infection with an ORFV that was closely related genetically to Nantou (DQ934351), which was isolated from the Tai wan province of China and Hoping (EU935106), which originated from South Korea in 2008. This is the first report of the phylogenetic analysis of ORFV from goats in China.

A quantitative rabbit model of vaccinia keratitis.

PURPOSE: The goal of this study was to use multiple quantitative disease measures to evaluate the effect of various viral inocula on the development of vaccinia keratitis in rabbits. METHODS: Trephined eyes of female rabbits were infected with 10(4), 10(5), 10(6), or 10(7) plaque-forming units (pfu) of the Dryvax strain of the vaccinia virus and scored daily for disease for 14 days according to a modification of the MacDonald-Shadduck scoring system. Ocular viral titers and vaccinia-specific antibody titers were determined by plaque assay and ELISA, respectively. RESULTS: The amount of virus used for infection affected the severity of disease, with 10(4) pfu eliciting milder keratitis after delayed onset compared with higher amounts of virus. At inocula above 10(5) pfu the course and severity of corneal disease was not significantly different. The time to reach peak titers was delayed in the 10(4) group but peak titers were similar in all groups. Severe conjunctival chemosis interfered with scoring in animals infected with 10(6) or 10(7) pfu. Virus-specific antibody titers were similar in all groups at day 14. Body weights decreased less than 10% in all groups. CONCLUSIONS: The course of vaccinia keratitis in rabbits paralleled that in humans. A viral inoculum of 10(5) pfu/eye was determined to be optimal for use in further studies of vaccinia keratitis.