Non-human primates are the animals closest to humans for use in influenza A virus challenge studies, in terms of their phylogenetic relatedness, physiology and immune systems. Previous studies have shown that cynomolgus macaques (Macaca fascicularis) are permissive for infection with H1N1pdm influenza virus. These studies have typically used combined challenge routes, with the majority being intra-tracheal delivery, and high doses of virus (> 107 infectious units). This paper describes the outcome of novel challenge routes (inhaled aerosol, intra-nasal instillation) and low to moderate doses (103 to 106 plaque forming units) of H1N1pdm virus in cynomolgus macaques. Evidence of virus replication and sero-conversion were detected in all four challenge groups, although the disease was sub-clinical. Intra-nasal challenge led to an infection confined to the nasal cavity. A low dose (103 plaque forming units) did not lead to detectable infectious virus shedding, but a 1000-fold higher dose led to virus shedding in all intra-nasal challenged animals. In contrast, aerosol and intra-tracheal challenge routes led to infections throughout the respiratory tract, although shedding from the nasal cavity was less reproducible between animals compared to the high-dose intra-nasal challenge group. Intra-tracheal and aerosol challenges induced a transient lymphopaenia, similar to that observed in influenza-infected humans, and greater virus-specific cellular immune responses in the blood were observed in these groups in comparison to the intra-nasal challenge groups. Activation of lung macrophages and innate immune response genes was detected at days 5 to 7 post-challenge. The kinetics of infection, both virological and immunological, were broadly in line with human influenza A virus infections. These more authentic infection models will be valuable in the determination of anti-influenza efficacy of novel entities against less severe (and thus more common) influenza infections.

DERMOID sinus (also termed pilonidal sinus, pilonidal cyst or dermoid cyst) is a developmental anomaly characterised by incomplete separation of the skin from the neural tube during embryonic development (Lord and others 1957, Mann and Stratton 1966, Antin 1970. Six different types of dermoid sinus exist and classification is based on their relationship to the supraspinous ligament (Mann and Stratton 1966, Kiviranta and others 2011). This short communication describes the clinical, MRI and histopathological features of a type IV dermoid sinus and spina bifida in a young Victorian bulldog.An 11-month-old male Victorian bulldog was referred for investigation of progressive paraparesis, moderate hindlimb ataxia and moderate proprioceptive deficits in both hindlimbs. At physical examination, it was noted that the hair was growing in a spiral fashion on the dorsal midline in the mid-thoracic region. A small, fluctuating mass was palpable subcutaneously and evoked considerable pain for the dog; the mass was continuous with a firm fistulous cord attached to the underlying tissues. A round-shaped opening in the skin (diameter 0.5 cm) containing no exudates was found after clipping of the hair.Radiographs of the thoracic and thoracolumbar spine were unremarkable. MRI scans (Vet-MR Grande; Esaote) of the dog's thoracic region were obtained in three planes of orientation before and after the intravenous administration of 0.1 mmol/kg gadolinium (Magnevist; Schering). Transverse T1-weighted and T2-weighted images revealed an invagination of the epidermal and dermal tissues towards the spinous process of T8. A fistular tract was visible connecting the spinal cord with the opened skin layers. The normal morphology of T8 was lost: this vertebra lacked a normal vertebral arch and the spinous process seemed to be separated into two lateral sections between which the fistular tract lay. The spinal cord presented a diffuse and homogeneous hyperintense signal on T2-weighted images from T5 to T11. The MRI findings were consistent with a type IV dermoid sinus associated with spinal cord oedema and spina bifida at T8. Cisternal cerebrospinal fluid (CSF) analysis revealed mild albuminocytological dissociation, supporting the diagnosis of a compressive/traumatic lesion (Meinkoth and Crystal 1999). Aerobic and anaerobic culture was performed on CSF samples, which yielded no bacterial growth.Under general anaesthesia, the dog was positioned in sternal recumbency and the dorsal thoracic region was surgically prepared. After blunt dissection via the layers deep to the skin, a fistulous tube extending within the bone tissue of the spinous process of T8 was noted (Fig 1). A dorsal laminectomy was carried out and the spinal cord was exposed. The sinus tract extended into the spinal cord and the external sheath of the sinus was in continuity with the dura. The lumen of the fistular tract contained hair (Fig 2). A durotomy was carried out and the intraspinal sinus tract was excised, routinely fixed in formalin and submitted for histopathological ...

Murine γ-herpesvirus 68 (MHV-68) infection of Mus musculus-derived strains of mice is an attractive model of γ-herpesvirus infection. Surprisingly, however, ablation of expression of MHV-68 M3, a secreted protein with broad chemokine-binding properties in vitro, has no discernable effect during experimental infection via the respiratory tract. Here we demonstrate that M3 indeed contributes significantly to MHV-68 infection, but only in the context of a natural host, the wood mouse (Apodemus sylvaticus). Specifically, M3 was essential for two features unique to the wood mouse: virus-dependent inducible bronchus-associated lymphoid tissue (iBALT) in the lung and highly organized secondary follicles in the spleen, both predominant sites of latency in these organs. Consequently, lack of M3 resulted in substantially reduced latency in the spleen and lung. In the absence of M3, splenic germinal centers appeared as previously described for MHV-68-infected laboratory strains of mice, further evidence that M3 is not fully functional in the established model host. Finally, analyses of M3's influence on chemokine and cytokine levels within the lungs of infected wood mice were consistent with the known chemokine-binding profile of M3, and revealed additional influences that provide further insight into its role in MHV-68 biology.

The airway epithelium secretes proteins that function in innate defense against infection. BPI fold-containing family member A1 (BPIFA1) is secreted into airways and has a protective role during bacterial infections, but it is not known whether it also has an antiviral role. To determine a role in host defense against influenza A virus (IAV) infection and to find the underlying defense mechanism we developed transgenic mouse models that are deficient in BPIFA1 and used these, in combination with in vitro 3D mouse tracheal epithelial cell (mTEC) cultures, to investigate its antiviral properties. We show that BPIFA1 has a significant role in mucosal defense against IAV infection. BPIFA1 secretion was highly modulated after

The intestinal microbiota plays an essential role in the metabolism and immune competence of chickens from the first day after hatching. In modern production systems, chicks are isolated from adult chickens, instead hatching in a clean environment. As a result, chicks are colonized by environmental bacteria, including potential pathogens. There is a need to investigate methods by which chicks can be exposed to a more appropriate microbial community at hatching. Such methods must be easy to apply in a hatchery and produce consistent results. The development of the intestinal microbiota of chicks hatched from eggs sprayed with dilute adult cecal content during incubation was observed at 0, 3, 7, and 14 days posthatching (dph) across two experiments. High-throughput Illumina sequencing was performed for the V4 hypervariable region of the 16S rRNA gene. A topical treatment of dilute adult cecal content was sufficient to transplant spore-forming bacteria such as Lachnospiraceae and Ruminococcaceae. However, this treatment was not able to transplant other taxa that are considered to be core elements of the chicken cecal microbiota, such as Bacteroidaceae, Lactobacillaceae, Bifidobacteriaceae, and Burkholderiaceae. The topical treatment significantly altered the microbiota of chicks immediately posthatching and accelerated the normal development of the microbiota with earlier colonization by Ruminococcaceae in the cecum and “Candidatus Arthromitus” in the ileum. The effect of the treatment on the cecal microbiota was maximal at 3 dph but diminished over time. IMPORTANCE Over the last 60 years poultry production has intensified in response to increased demand for meat. In modern systems, chicks hatch without contacting chickens and their gut bacteria. Consequently, they are colonized by environmental bacteria that may cause disease. The normal bacteria that live in the gut, or intestinal microbiota, play an important role in the development of the immune system. Therefore, it is essential to find easy ways to expose chicks to the more appropriate bacteria at hatching. This experiment investigated whether spraying eggs with adult cecal contents was sufficient to transfer an adult microbiota to chicks. Our findings show that spore-forming bacteria were transplanted, but other members of the microbiota were not. In this respect, the spray application was partially successful, but the timing of the spray needs to be modified to ensure that more bacteria are transferred.

Feline herpesvirus type 1 (FeHV-1) is one of the etiological agents of feline respiratory disease. FeHV-1 is an epitheliotropic and cytopathic virus that mainly causes rhinitis and conjunctivitis, although pneumonia is also occasionally seen. In this study, the authors investigated the pathogenesis of FeHV-1-associated pneumonia, comparing natural cases with viral infection of tracheal ring and cell cultures in vitro, using histology, immunohistology, double immunofluorescence, and transmission electron microscopy as investigative tools. The results confirm that FeHV-1 targets both respiratory epithelial cells and pneumocytes and indicate that FeHV-1 pneumonia is the consequence of continuous cell-to-cell viral spread from the upper airways via the trachea into the lungs. They provide strong evidence that FeHV-1-infected cells die primarily via apoptosis, following loss of cell-to-cell contact, rounding, and detachment. However, virus-induced lesions in vivo are dominated by marked neutrophil infiltration and extensive necrosis with less prominent apoptosis; in the airways, the tissue necrosis can extend into the submucosa. The necrosis appears to result from virus-induced neutrophil influx and release of proteolytic enzymes, such as matrix metalloproteinase-9, from the neutrophils.

FIG 1: Cut surface of an ulcerated polypoid lesion surgically excised from the nasal mucosa of a six-year-old polo pony. Bar=4 mm FIG 2: Juvenile sporangia (arrows). Predominantly spherical structures with a thick, eosinophilic wall, enclosing fibrillar material and surrounded by a lymphoplasmacellular infiltrate. Haematoxylin and eosin. x 40

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