VIRUS DISSEMINATION THROUGH THE BRAIN PARENCHYMA WITHOUT IMMUNOLOGICAL CONTROL

After inoculation into the cerebrospinal fluid, the neurovirulent infl uenza virus A/WSN caused a rapidly progressive encephalitis that was u niformly fatal within 8 days, After inoculation into the brain parench yma, the same virus replicated for 7 to 20 days without causing clinic al illness, but when infection reached the cerebrospinal fluid, enceph alitis was lethal within a further 6 days, As the virus spread through the brain parenchyma, there was intense intracerebral inflammation, w ith up-regulation of MHC class I and MHC class II expression and recru itment of CD44(high) CD49d(high) T cells, However, this was not associ ated with antiviral Ab production, and the infiltrating cells, unlike primed A/WSN-specific T cells, did not eliminate the virus in vivo or show evidence of virus recognition in vitro. Thus, a neurovirulent vir us was able to disseminate widely through the brain parenchyma and ind uce considerable intracerebral inflammation without eliciting protecti ve immunity.