Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis

Pedersen, Niels C; Kim, Yunjeong; Liu, Hongwei; Galasiti Kankanamalage, Anushka C; Eckstrand, Chrissy; Groutas, William C; Bannasch, Michael; Meadows, Juliana M; Chang, Kyeong-Ok

The high incidence of central nervous system (CNS) diseases in this study was greater than previously reported and unexpected given that cats with signs of brain or spinal cord involvement were excluded from the trial. 20 CNS disease was much more likely to occur in older cats with dry or dry-to-wet disease than in young cats with wet FIP. This indicates that FIPV can enter the brain in many cats, if given enough time. Infection of the CNS appears to involve peritoneal-type macrophages, as FIPV-infected cells in the brains of cats with neurologic FIP more closely resemble peritoneal rather than resident brain macrophages. 18, 19 This should not be surprising, as macrophages migrate to various tissues, including the brain, to carry out immune surveillance and are also targets for a range of infectious agents, such as FIPV and HIV-1. Infected macrophages play a major role in viral dissemination to the brain in patients with HIV and detection of virus in the brain can occur within weeks of infection. 21, 22 However, neurologic impairment usually occurs at a later stage. Anti-HIV drugs also reduce the frequency of severe neurologic impairment, 23 as observed with FIPV and GC376 in the present study. There are also alternative explanations. It is possible that extra-CNS involvement may inhibit the development of brain disease and vice versa. It is common to see CNS disease occur in the absence of visceral disease and vice versa. 13, 20 Suppressing viral replication in the nonneuronal tissues may also enhance positive selection for mutants that are more neurotropic or neurovirulent. However, proof for the latter would require considerable studies using laboratory cats.