Autophagy in α-Synucleinopathies—An Overstrained System

Alpha-synucleinopathies comprise progressive neurodegenerative diseases, including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). They all exhibit the same pathological hallmark, which is the formation of α-synuclein positive deposits in neuronal or glial cells. The aggregation of α-synuclein in the cell body of neurons, giving rise to the so-called Lewy bodies (LBs), is the major characteristic for PD and DLB, whereas the accumulation of α-synuclein in oligodendroglial cells, so-called glial cytoplasmic inclusions (GCIs), is the hallmark for MSA. The mechanisms involved in the intracytoplasmic inclusion formation in neuronal and oligodendroglial cells are not fully understood to date. A possible mechanism could be an impaired autophagic machinery that cannot cope with the high intracellular amount of α-synuclein. In fact, different studies showed that reduced autophagy is involved in α-synuclein aggregation. Furthermore, altered levels of different autophagy markers were reported in PD, DLB, and MSA brains. To date, the trigger point in disease initiation is not entirely clear; that is, whether autophagy dysfunction alone suffices to increase α-synuclein or whether α-synuclein is the pathogenic driver. In the current review, we discuss the involvement of defective autophagy machinery in the formation of α-synuclein aggregates, propagation of α-synuclein, and the resulting neurodegenerative processes in α-synucleinopathies.

Lumpy Skin Disease Is Characterized by Severe Multifocal Dermatitis With Necrotizing Fibrinoid Vasculitis Following Experimental Infection

Lumpy skin disease is a high-consequence disease in cattle caused by infection with the poxvirus lumpy skin disease virus (LSDV). The virus is endemic in most countries in Africa and an emerging threat to cattle populations in Europe and Asia. As LSDV spreads into new regions, it is important that signs of disease are recognized promptly by animal caregivers. This study describes the gross, microscopic, and ultrastructural changes that occur over time in cattle experimentally challenged with LSDV. Four calves were inoculated with wildtype LSDV and monitored for 19 to 21 days. At 7 days after inoculation, 2 of the 4 cattle developed multifocal cutaneous nodules characteristic of LSD. Some lesions displayed a targetoid appearance. Histologically, intercellular and intracellular edema was present in the epidermis of some nodules. Occasional intracytoplasmic inclusion bodies were identified in keratinocytes. More severe and consistent changes were present in the dermis, with marked histiocytic inflammation and necrotizing fibrinoid vasculitis of dermal vessels, particularly the deep dermal plexus. Chronic lesions consisted of full-thickness necrosis of the dermis and epidermis. Lesions in other body organs were not a major feature of LSD in this study, highlighting the strong cutaneous tropism of this virus. Immunohistochemistry and electron microscopy identified LSDV-infected histiocytes and fibroblasts in the skin nodules of affected cattle. This study highlights the noteworthy lesions of LSDV and how they develop over time.

Novel characteristics identified in two cases of feline cowpox virus infection

Case series summary This case series discusses novel characteristics identified in two cases of cowpox. One presented with upper airway signs, and was identified to have a focal laryngeal lesion. The other had central neurological signs at the terminal stages, with intracytoplasmic inclusion bodies identified within the cerebral hemispheres on histopathology. Relevance and novel information Currently, cowpox would be an unlikely consideration in patients with neurological signs or upper respiratory noise. These cases both document novel presentations of cowpox infection, which clinicians should be aware of and consider as differential diagnoses in patients with these atypical presentations.

Avian poxvirus in a free-range juvenile speckled (rock) pigeon (Columba guinea)

A flightless wild juvenile rock pigeon (Columba guinea) with pox-like lesions was picked up on the premises of the Faculty of Veterinary Science, University of Pretoria, Onderstepoort. The pigeon was housed overnight for possible treatment the following day but died before any other intervention could be instituted. At necropsy, coalescing masses of yellowish nodular cutaneous tumour-like lesions principally on the featherless areas were noticed on the dead pigeon’s head as well as the beak. Histological examination of the sampled skin lesions revealed multifocal areas of hypertrophic and hyperplastic epidermal epithelial cells with eosinophilic intracytoplasmic inclusion bodies (Bollinger bodies). Extract from the lesion was processed and inoculated on the chorioallantoic membranes (CAM) of 11-day-old embryonated chicken eggs and this produced pocks on one of the CAM at day 7 post-inoculation. Electron microscopy confirmed the presence of poxvirus in the CAM with the pock lesions.

A Case of Contagious Ecthyma (Orf Virus) in a Nonmanipulated Laboratory Dorset Sheep (Ovis aries)

An approximately 5-month-old laboratory wether, originating from a local vendor with a closed flock and maintained on a preventative medicine plan, presented with a continuum of lesions from hemorrhagic papules, vesicles, and pustules, to multifocal necrotic scabs at the commissure of the lips, medial canthus of the left eye, and distal prepuce. A presumptive diagnosis of Orf virus (ORFV) was made and the sheep was euthanized. A full necropsy was performed, and histopathological evaluation of affected tissues revealed multifocal-to-coalescing necrotizing and proliferative cheilitis and dermatitis with eosinophilic intracytoplasmic inclusion bodies. Electron microscopy findings revealed degenerate keratinocytes containing numerous typical 200–300 nm wide cytoplasmic parapoxvirus virions, confirming the diagnosis of ORFV. We believe that this animal developed a clinical case of ORFV either due to an adverse reaction to an ORFV vaccine, or this animal had a case of preexisting ORFV which manifested after arrival at our facility.