Infección experimental por herpesvirus bovino 1 en conejas gestantes

Natural infection with Bovine herpesvirus 1 (BoHV-1) produces several clinical manifestations including conjunctivitis, respiratory signs, genital diseases and abortion. The rabbit is a good model for studying of latency, pathogenicity of BoHV-5 and other bovine herpesviruses. This study was conducted in order to analyze the response to experimental infection with BoHV-1 in rabbits during different periods of pregnancy. The results obtained could be useful for better understanding of the infection in cattle. A new method of infection was used. The rabbits developed clinical signs. The virus was recovered from nasal swabs and histological lesions were found in the analyzed samples. The humoral response was demonstrated and viral DNA was detected from the placentas. This work showed for the first time the arrival of BoHV-1 to blood after intranasal infection with the virus. It also provides a useful tool that can be used to evaluate the pathogenicity of by BoHV-1 strains, the immune response and to study viral latency and reactivation.La infección natural por Herpesvirus bovino 1 (BoHV-1) se manifiesta por conjuntivitis, signos respiratorios (rinotraqueitis), lesiones genitales (vulvovaginitis pustular infecciosa o balanopostitis) y abortos. El conejo, hasta el momento, ha resultado ser el mejor modelo experimental para estudiar los diferentes aspectos de la infección por BoHV-1, el fenómeno de latencia, la neuropatogenicidad de BoHV-5 y el comportamiento de diferentes cepas virales. Este trabajo se desarrolló con el objetivo de estudiar la respuesta de conejas infectadas con BoHV-1 en diferentes períodos de la gestación para que los datos resultantes puedan ser utilizados para la mejor comprensión de la infección en el bovino. Se utilizó un nuevo método de infección intranasal. Los animales desarrollaron signos clínicos. Se recuperó virus a partir de hisopados nasales, se observaron lesiones histopatológicas en las muestras analizadas, se demostró la respuesta inmune humoral y se detectó ADN viral a partir de placentas de los animales gestantes infectados. En este trabajo se evidenció por primera vez en el modelo conejo la llegada del virus al torrente sanguíneo luego de la infección intranasal. Además se aporta una herramienta de utilidad que puede ser utilizada para evaluar la virulencia de diferentes cepas de BoHV-1 y la respuesta inmune a distintos inmunógenos como también para realizar estudios de latencia y reactivación

Effective Treatment of Respiratory Alphaherpesvirus Infection Using RNA Interference

BACKGROUND: Equine herpesvirus type 1 (EHV-1), a member of the Alphaherpesvirinae, is spread via nasal secretions and causes respiratory disease, neurological disorders and abortions. The virus is a significant equine pathogen, but current EHV-1 vaccines are only partially protective and effective metaphylactic and therapeutic agents are not available. Small interfering RNAs (siRNA's), delivered intranasally, could prove a valuable alternative for infection control. siRNA's against two essential EHV-1 genes, encoding the viral helicase (Ori) and glycoprotein B, were evaluated for their potential to decrease EHV-1 infection in a mouse model. METHODOLOGY/PRINCIPAL FNDINGS: siRNA therapy in vitro significantly reduced virus production and plaque size. Viral titers were reduced 80-fold with 37.5 pmol of a single siRNA or with as little as 6.25 pmol of each siRNA when used in combination. siRNA therapy in vivo significantly reduced viral replication and clinical signs. Intranasal treatment did not require a transport vehicle and proved effective when given up to 12 h before or after infection. CONCLUSIONS/SIGNIFICANCE: siRNA treatment has potential for both prevention and early treatment of EHV-1 infections

First molecular detection of co-infection of honey bee viruses in asymptomatic Bombus atratus in South America

Pollination is critical for food production and has the particularity of linking natural ecosystems with agricultural production systems. Recently, losses of bumblebee species have been reported worldwide. In this study, samples from a commercial exploitation of bumblebees of Argentina with a recent history of deaths were studied using a multiplex PCR for the detection of the honey bee viruses most frequently detected in South America. All samples analysed were positive for co-infections with Deformed wing virus, Black queen cell virus and Sacbrood virus. This is the first report of infection of Bombus atratus with honey bee viruses. A better understanding of viral infections in bumblebees and of the epidemiology of viruses could be of great importance as bumblebees can serve as possible viral reservoirs, resulting in pathogen spillover towards honey bees and native bumblebees

First molecular detection of co-infection of honey bee viruses in asymptomatic Bombus atratus in South America

Pollination is critical for food production and has the particularity of linking natural ecosystems with agricultural production systems. Recently, losses of bumblebee species have been reported worldwide. In this study, samples from a commercial exploitation of bumblebees of Argentina with a recent history of deaths were studied using a multiplex PCR for the detection of the honey bee viruses most frequently detected in South America. All samples analysed were positive for co-infections with Deformed wing virus, Black queen cell virus and Sacbrood virus. This is the first report of infection of Bombus atratus with honey bee viruses. A better understanding of viral infections in bumblebees and of the epidemiology of viruses could be of great importance as bumblebees can serve as possible viral reservoirs, resulting in pathogen spillover towards honey bees and native bumblebees

KMT2B-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation

Heterozygous mutations in KMT2B are associated with an early-onset, progressive and often complex dystonia (DYT28). Key characteristics of typical disease include focal motor features at disease presentation, evolving through a caudocranial pattern into generalized dystonia, with prominent oromandibular, laryngeal and cervical involvement. Although KMT2B-related disease is emerging as one of the most common causes of early-onset genetic dystonia, much remains to be understood about the full spectrum of the disease. We describe a cohort of 53 patients with KMT2B mutations, with detailed delineation of their clinical phenotype and molecular genetic features. We report new disease presentations, including atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype. In addition to the previously reported systemic features, our study has identified co-morbidities, including the risk of status dystonicus, intrauterine growth retardation, and endocrinopathies. Analysis of this study cohort (n = 53) in tandem with published cases (n = 80) revealed that patients with chromosomal deletions and protein truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants. Eighteen individuals had detailed longitudinal data available after insertion of deep brain stimulation for medically refractory dystonia. Median age at deep brain stimulation was 11.5 years (range: 4.5–37.0 years). Follow-up after deep brain stimulation ranged from 0.25 to 22 years. Significant improvement of motor function and disability (as assessed by the Burke Fahn Marsden’s Dystonia Rating Scales, BFMDRS-M and BFMDRS-D) was evident at 6 months, 1 year and last follow-up (motor, P = 0.001, P = 0.004, and P = 0.012; disability, P = 0.009, P = 0.002 and P = 0.012). At 1 year post-deep brain stimulation, >50% of subjects showed BFMDRS-M and BFMDRS-D improvements of >30%. In the long-term deep brain stimulation cohort (deep brain stimulation inserted for >5 years, n = 8), improvement of >30% was maintained in 5/8 and 3/8 subjects for the BFMDRS-M and BFMDRS-D, respectively. The greatest BFMDRS-M improvements were observed for trunk (53.2%) and cervical (50.5%) dystonia, with less clinical impact on laryngeal dystonia. Improvements in gait dystonia decreased from 20.9% at 1 year to 16.2% at last assessment; no patient maintained a fully independent gait. Reduction of BFMDRS-D was maintained for swallowing (52.9%). Five patients developed mild parkinsonism following deep brain stimulation. KMT2B-related disease comprises an expanding continuum from infancy to adulthood, with early evidence of genotype-phenotype correlations. Except for laryngeal dysphonia, deep brain stimulation provides a significant improvement in quality of life and function with sustained clinical benefit depending on symptoms distribution