Bluetongue in Belgium, 2006

Bluetongue has emerged recently in Belgium. A bluetongue virus strain was isolated and characterized as serotype 8. Two new real-time reverse transcription–quantitative PCRs (RT-qPCRs) that amplified 2 different segments of bluetongue virus detected this exotic strain. These 2 RT-qPCRs detected infection earlier than a competitive ELISA for antibody detection

Classical swine fever outbreak containment using antivirals: a potential alternative to emergency vaccination and stamping-out

Classical swine fever (CSF) outbreaks may result in huge economic losses to countries with densely populated pig areas (DPLAs). The EU minimum control measures require depopulation of infected farms, movement restrictions, zoning and surveillance (EU Minimum strategy). Emergency vaccination is authorised for DPLAs although the EU Minimum strategy plus culling in a 1-km ring around infected premises is preferred. Nonetheless, vaccination in a 2-km ring has been found equally effective as 1-km ring culling using stochastic modelling. Alternatives control measures (e.g. antiviral agents, in particular small molecule inhibitors of the CSFV replication) are being explored. Hence, the present study was set up to simulate inter-herd CSFV spread when antiviral molecules are supplemented to pig feed in a 1-km ring around infected farms. The effectiveness of the antiviral strategy for containing CSF outbreaks was compared to six other control scenarios including the EU Minimum strategy, the EU preferred policy for DPLAs and the use of 2-km ring vaccination. The InterSpread Plus model was adapted to the 2006 Belgian pig population and outbreak simulations were performed with a fast spreading CSFV strain entering a DPLA in Belgium. Four out of the seven control strategies resulted in outbreaks that were controlled by the end of the simulation period (i.e. 365 days). The distributions of the number of infected herds and the duration of the predicted outbreaks for these four control strategies were not different. This is the first report investigating CSF outbreak containment using antiviral molecules. Although antiviral supplementation was not found to perform any better than some other conventional strategies, such as pre-emptive culling and emergency vaccination, it might be worthwhile considering it further as additional tool in a response to CSF outbreaks.status: publishe

Corticotropin-releasing hormone (CRH)-induced thyrotropin release is directly mediated through CRH receptor type 2 on thyrotropes

CRH is known as the main stimulator of ACTH release. In representatives of all nonmammalian vertebrates, CRH has also been shown to induce TSH secretion, acting directly at the level of the pituitary. We have investigated which cell types and receptors are involved in CRH-induced TSH release in the chicken (Gallus gallus). Because a lack of CRH type 1 receptors (CRH-R1) on the chicken thyrotropes has been previously reported, two hypotheses were tested using in situ hybridization and perifusion studies: 1) TSH secretion might be induced in a paracrine way involving melanocortins from the corticotropes; and 2) thyrotropes might express another type of CRH-R. For the latter, we have cloned a partial cDNA encoding the chicken CRH-R2. Neither alpha-melanotropin (alpha-MSH) nor its powerful analog Nle(4), D-Phe(7)-MSH could mimic the in vitro TSH-releasing effect of ovine CRH. The nonselective melanocortin receptor blocker SHU91199 did not influence CRH- or TRH-induced TSH secretion. On the other hand, we have found that thyrotropes express CRH-R2 mRNA. The involvement of this CRH receptor in the response of thyrotropes to CRH was further confirmed by the fact that TSH release was stimulated by human urocortin III, a CRHR2-specific agonist, whereas the TSH response to CRH was completely blocked by the CRH- R blocker astressin and the CRH-R2- specific antagonist antisauvagine-30. We conclude that CRH- induced TSH secretion is mediated by CRH-R2 expressed on thyrotropes.status: publishe

Evaluation of a modified Karnofsky score to assess physical and psychological wellbeing of cats in a hospital setting

Objectives: The Karnofsky score (KS) modified for cats, a scoring system to rate health and quality of life (QOL) in cats, is used in clinical trials, but its reliability and validity are yet to be determined. The present study aims to evaluate the scientific robustness of the KS when adapted for use in a hospital setting. Methods: A list of variables to consider during the physical examination, which informs the clinician's score (CS) part of the KS, was added and clinicians were allowed to choose a score anywhere between 0 and 50. The Karnofsky QOL questionnaire was adapted for use in a hospital setting. F-tests with Bonferroni correction and Spearman rank correlation coefficients were used to evaluate reliability and validity of the KS to assess the health and wellbeing of cats in a hospital setting. The records of 54 feline immunodeficiency virus-positive cats, which were recruited for a clinical trial and hospitalised for 6 weeks, were reviewed. Four veterinarians scored the CS, and one veterinarian and a veterinary nurse assessed the QOL score. Results: Mean absolute difference between observers was significantly larger for the CS than for the QOL score (P <0.001) and two veterinarians scored significantly higher than the remaining two veterinarians (P <0.001). Inter-observer correlation ranged from 0.45-0.75 for the CS. For the QOL score, the absolute difference between observers was small, no significant difference was found between observers and a high degree of inter-observer correlation was noted (r = 0.91). Conclusions and relevance: The results indicate low inter-observer reliability for the CS, requiring additional modifications to this part of the KS. The QOL score seems more reliable, and the questionnaire may serve as a reliable tool in the assessment of QOL in cats in a hospital setting. Consequently, further adaptation of the KS is mandatory when simultaneous assessment of both the cat's clinical health and perceived wellbeing is required

Modulating mouse innate immunity to RNA viruses by expressing the Bos taurus Mx system.

Mx proteins are interferon-induced members of the dynamin superfamily of large guanosine triphosphatases. These proteins have attracted much attention because some display antiviral activity against pathogenic RNA viruses, such as members of the orthomyxoviridae, bunyaviridae, and rhabdoviridae families. Among the diverse mammalian Mx proteins examined so far, we have recently demonstrated in vitro that the Bos taurus isoform 1 (boMx1) is endowed with exceptional anti-rabies-virus activity. This finding has prompted us to seek an appropriate in vivo model for confirming and evaluating gene therapy strategies. Using a BAC transgene, we have generated transgenic mouse lines expressing the antiviral boMx1 protein and boMx2 proteins under the control of their natural promoter and short- and long-range regulatory elements. Expressed boMx1 and boMx2 are correctly assembled, as deduced from mRNA sequencing and western blotting. Poly-I/C-subordinated expression of boMx1 was detected in various organs by immunohistochemistry, and transgenic lines were readily classified as high- or low-expression lines on the basis of tissue boMx1 concentrations measured by ELISA. Poly-I/C-induced Madin-Darby bovine kidney cells, bovine turbinate cells, and cultured cells from high-expression line of transgenic mice were found to contain about the same concentration of boMx1, suggesting that this protein is produced at near-physiological levels. Furthermore, insertion of the bovine Mx system rendered transgenic mice resistant to vesicular-stomatitis-virus-associated morbidity and mortality, and embryonic fibroblasts derived from high-expression transgenic mice were far less permissive to the virus. These results demonstrate that the Bos taurus Mx system is a powerful anti-VSV agent in vivo and suggest that the transgenic mouse lines generated here constitute a good model for studying in vivo the various antiviral functions-known and yet to be discovered-exerted by bovine Mx proteins, with priority emphasis on the antirabic function of boMx1

Antiviral treatment of feline immunodeficiency virus-infected cats with (R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine

Feline immunodeficiency virus (FIV), the causative agent of an acquired immunodeficiency syndrome in cats (feline AIDS), is an ubiquitous health threat to the domestic and feral cat population, also triggering disease in wild animals. No registered antiviral compounds are currently available to treat FIV-infected cats. Several human antiviral drugs have been used experimentally in cats, but not without the development of serious adverse effects. Here we report on the treatment of six naturally FIV-infected cats, suffering from moderate-to-severe disease, with the antiretroviral compound (R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine ([R]-PMPDAP), a close analogue of tenofovir, a widely prescribed anti-HIV drug in human medicine. An improvement in the average Karnofsky score (pretreatment 33.2 ± 9.4%, post-treatment 65±12.3%), some laboratory parameters (ie, serum amyloid A and gammaglobulins) and a decrease of FIV viral load in plasma were noted in most cats. The role of concurrent medication in ameliorating the Karnofsky score, as well as the possible development of haematological side effects, are discussed. Side effects, when noted, appeared mild and reversible upon cessation of treatment. Although strong conclusions cannot be drawn owing to the small number of patients and lack of a placebo-treated control group, the activity of (R)-PMPDAP, as observed here, warrants further investigation