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Feline panleukopenia virus in cerebral neurons of young and adult cats.

ABSTRACT: Perinatal infections with feline panleukopenia virus (FPV) have long been known to be associated with cerebellar hypoplasia in kittens due to productive infection of dividing neuroblasts. FPV, like other parvoviruses, requires dividing cells to replicate which explains the usual tropism of the virus for the digestive tract, lymphoid tissues and bone marrow in older animals.In this study, the necropsy and histopathological analyses of a series of 28 cats which died from parvovirus infection in 2013 were performed. Infections were confirmed by real time PCR and immunohistochemistry in several organs. Strikingly, while none of these cats showed cerebellar atrophy or cerebellar positive immunostaining, some of them, including one adult, showed a bright positive immunostaining for viral antigens in cerebral neurons (diencephalon). Furthermore, infected neurons were negative by immunostaining for p27(Kip1), a cell cycle regulatory protein, while neighboring, uninfected, neurons were positive, suggesting a possible re-entry of infected neurons into the mitotic cycle. Next-Generation Sequencing and PCR analyses showed that the virus infecting cat brains was FPV and presented a unique substitution in NS1 protein sequence. Given the role played by this protein in the control of cell cycle and apoptosis in other parvoviral species, it is tempting to hypothesize that a cause-to-effect between this NS1 mutation and the capacity of this FPV strain to infect neurons in adult cats might exist.This study provides the first evidence of infection of cerebral neurons by feline panleukopenia virus in cats, including an adult. A possible re-entry into the cell cycle by infected neurons has been observed. A mutation in the NS1 protein sequence of the FPV strain involved could be related to its unusual cellular tropism. Further research is needed to clarify this point.

SUBMITTER: Garigliany M

PROVIDER: S-EPMC4759964 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Project description:Forty diseased cats and seven healthy control cats from different sex, ages and breeds had examined clinically to confirm presence or absence of clinical symptoms of Feline panleukopenia disease (FP). Several tools including ELISA, gene expression analysis (qRT-PCR), DNA fragmentation test and apoptosis assay were conducted to determine the Feline panleukopenia disease in cat tissues. Clinical symptoms in the form of depression, fever, anorexia, vomiting, diarrhea, dehydration, anaemia and leucopenia were recorded in the diseased cats while no clinical sings were observed in control healthy cats. ELISA results showed that all of diseased (n?=?40) cats were positive while control cats (n?=?7) were negative for FP viral antigen. After carrying out of ELISA assay, supportive treatment trials including fluid therapy, immunostimulant, antibiotics to overcome dehydration, restoring electrolytes imbalances, combating secondary bacterial infection were conducted but all diseased cats were died and control cats exposed to soft death. Gene expression analysis detected high levels of FP viral gene in several cat tissues in which ilium exhibited high viral expression levels compared with jejunum. Also, viral expression levels in jejunum were higher than in mesenteric lymph nodes. In addition, viral expression levels were not detected in tissues of control cats. The results of the DNA fragmentation assay observed that DNA extracted from different tissues of infected cats exhibited damaged DNA bands as compared with DNA of control cats. DNA fragmentation rates in infected tissues increased significantly (P?<?0.01), the highest rates were showed in ilium and jejunum tissue than in mesenteric lymph nodes. Determination of apoptosis in cat tissues showed that rate of apoptosis/necrosis increased significantly (P?<?0.05) in infected cats tissues in comparison to control cats. Moreover the highest apoptotic ratios of infected cats were observed in ilium and jejunum tissues compared with mesenteric lymph nodes.

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Feline panleukopenia virus in cerebral neurons of young and adult cats.

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