Cell cycle S phase markers are expressed in cerebral neuron nuclei of cats infected by the Feline Panleukopenia Virus.
The cell cycle-associated neuronal death hypothesis, which has been proposed as a common mechanism for most neurodegenerative diseases, is notably supported by evidencing cell cycle effectors in neurons. However, in naturally occurring nervous system diseases, these markers are not expressed in neuron nuclei but in cytoplasmic compartments. In other respects, the Feline Panleukopenia Virus (FPV) is able to complete its cycle in mature brain neurons in the feline species. As a parvovirus, the FPV is strictly dependent on its host cell reaching the cell cycle S phase to start its multiplication. In this retrospective study on the whole brain of 12 cats with naturally-occurring, FPV-associated cerebellar atrophy, VP2 capsid protein expression was detected by immunostaining not only in some brain neuronal nuclei but also in neuronal cytoplasm in 2 cats, suggesting that viral mRNA translation was still occurring. In these cats, double immunostainings demonstrated the expression of cell cycle S phase markers cyclin A, cdk2 and PCNA in neuronal nuclei. Parvoviruses are able to maintain their host cells in S phase by triggering the DNA damage response. S139 phospho H2A1, a key player in the cell cycle arrest, was detected in some neuronal nuclei, supporting that infected neurons were also blocked into the S phase. PCR studies did not support a co-infection with an adeno or herpes virus. ERK1/2 nuclear accumulation was observed in some neurons suggesting that the ERK signaling pathway might be involved as a mechanism driving these neurons far into the cell cycle.
a Laboratory of Anatomy, Biomechanics and Organogenesis, Faculty of Medicine, Université Libre de Bruxelles , Brussels , Belgium.|b ULB Neuroscience Insitute (UNI) , Brussels , Belgium.
Luc
L
Poncelet
c Morphology and Pathology, Faculty of Veterinary Medicine, University of Liège , Liège , Belgium.
Mutien
M
Garigliany
b ULB Neuroscience Insitute (UNI) , Brussels , Belgium.|d Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, Université Libre de Bruxelles , Brussels , Belgium.
Kunie
K
Ando
c Morphology and Pathology, Faculty of Veterinary Medicine, University of Liège , Liège , Belgium.
Mathieu
M
Franssen
c Morphology and Pathology, Faculty of Veterinary Medicine, University of Liège , Liège , Belgium.
Daniel
D
Desmecht
b ULB Neuroscience Insitute (UNI) , Brussels , Belgium.|d Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, Université Libre de Bruxelles , Brussels , Belgium.
Jean-Pierre
JP
Brion
D000818:Animals; D000914:Antibodies, Viral / Q000378:metabolism; D000918:Antibody Specificity; D020029:Base Pairing; D015415:Biomarkers / Q000378:metabolism*; D036022:Capsid Proteins / Q000378:metabolism; D002415:Cats; D002467:Cell Nucleus / Q000201:enzymology / Q000378:metabolism*; D054022:Cerebrum / Q000473:pathology*; D004279:DNA, Viral / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005254:Feline Panleukopenia / Q000473:pathology* / Q000821:virology*; D028301:Feline Panleukopenia Virus / Q000235:genetics / Q000502:physiology*; D005260:Female; D005814:Genes, Viral; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000473:pathology* / Q000821:virology; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D016196:S Phase; D013788:Thalamus / Q000378:metabolism
D000914:Antibodies, Viral; D015415:Biomarkers; D036022:Capsid Proteins; D004279:DNA, Viral; D048049:Extracellular Signal-Regulated MAP Kinases
DNA damage response; ERK pathway; cat; feline panleukopenia virus; neurodegeneration; neuronal cell cycle reentry; parvovirus