Evidence of parvovirus replication in cerebral neurons of cats

Abstract

The correlation between parvovirus infections and lesions in the central nervous system other than cerebellar hypoplasia was studied in 100 cats. The animals were necropsied with a history of various diseases, one third showing typical clinical and pathomorphological signs of panleukopenia. In 18 cats polyclonal antiserum against canine parvovirus consistently labeled neurons mainly in diencephalic regions, whereas the cerebellar cortex remained negative in all cases. In situ hybridization with digoxigenin-labeled minus-sense RNA probes, hybridizing with monomer-replicative form DNA or mRNA, revealed positive signals in nuclei of several neurons of the brain, again excluding the cerebellum. PCR applied to formalin-fixed and paraffin-embedded brain tissue and intestinal tissues of the diseased cats and subsequent DNA sequence analysis yielded canine parvovirus type 2 (CPV-2)-like sequences in the central nervous system. Two aspects of these findings are intriguing: (i). parvoviruses appear to be capable of replicating in neurons, cells that are considered to be terminally differentiated and (ii). CPV-like viruses of the old antigenic type CPV-2 appear to be able to infect cats.

FIG. 1.

Aspects of the LGN in a parvovirus-positive cat brain. (A) Degenerated neurons within the LGN (H&E staining); (B) positive, dark blue hybridization signal in two neuronal nuclei (arrows) detected by using a minus-sense RNA probe (in situ hybridization); and (C) intense brownish immunostaining of numerous neurons of the LGN detected by using polyclonal antibodies against CPV (IHC). All bars = 45 μm.

FIG. 2.

Agarose gel electrophoresis (2%) of PCR-amplified DNA from parvovirus-infected cats. This representative gel shows a size marker (1-kb DNA ladder, lane 1) and amplicons from cat 2 (lane 3) and cat 3 (lane 4), as well as negative controls (brain from a horse [lane 5] and aqua bidest [lane 6]) and CPV-d as a positive control (lane 7). The arrow points to the very weak band of cat 2; from cat 6 (lane 2) no DNA could be amplified.