PhD Thesis Demeter Zoltan

3.1.2.2 CNS infection
The spread of the virus to the CNS depends on the degree of systemic immune
responses mounted by the host. Virus probably enters the nervous system of many
viremic CDV-infected dogs whether neurologic signs are observed or not (Greene &
Appel, 2006). Generally, a polio- and a leukoencephalitis, characterized by different
distribution patterns of the lesions and pathogenesis, can be distinguished (Beineke et
al., 2009).
Primary spread of CDV to the CNS is hematogenous (Greene & Appel, 2006).
Studies tracking the route of CDV within the brain showed ependymal and
subependymal white matter infection, indicating CNS spread along the CSF pathway
(Vandevelde et al., 1985). A study using experimentally infected ferrets also suggests an
olfactory nerve pathway for the neuroinvasion (Rudd et al., 2006). A direct spread from
meningeal cells of the pia mater has been discussed (Baumgärtner et al., 1989).
Both a cell-free viremia during the first days following experimental infection
and a cell-associated virus spread have been described (Summers & Appel, 1987).
However, free infectious plasma virus cannot be observed after the appearance of virus-
neutralizing antibodies. The leukocyte-associated viremia is believed to represent the
major source of hematogenous infectivity. Viral antigen is first detected within CNS
capillaries and venular endothelia at 5 and 6 days p.i. and/or in perivascular
lymphocytes, astrocytic foot processes and pericytes at 8 days p.i. Furthermore, a
productive CDV infection of the choroid plexus epithelium with release of progeny
virus into the CSF followed by ependymal infection and spread of the virus to the
subependymal white matter can be observed at 10 days p.i. (Beineke et al., 2009).
The type of lesion produced as well as the course and outcome of the infection
within the CNS depend on numerous factors, such as the age and immunocompetence
of the host at the time of exposure, the neurotropic and immunosuppressive properties
of the virus, and the time at which lesions are examined (Greene & Appel, 2006).
• Acute infection
Acute CDV encephalitis, which occurs early in the course of infection in young or
immunosuppressed animals, is characterized by direct viral replication and injury: virus
antigen and messenger RNA (mRNA) are detected in lesions, whereas inflammatory
cells and class II MHC antigen expression are absent or minimal. Virus causes
multifocal lesions in the gray (neuronal infection and necrosis) and white matter
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