Natural History of a Recurrent Feline Coronavirus Infection and the Role of Cellular Immunity in Survival and Disease

摘要: The genus Coronavirus (family Coronaviridae, order Nidovirales) comprises a group of enveloped positive-strand RNA viruses mammals and birds. With genome 27 to 31 kb, encoding an ∼750-kDa pp1ab replicase polyprotein, four structural proteins (S, M, N, E) up five accessory nonstructural proteins, coronaviruses (CoVs) are the largest known date (5, 11). In humans, they mostly associated with mild enteric or respiratory infections, such as common cold, hence were long considered modest clinical importance. However, sudden emergence severe acute syndrome (SARS) has sparked wide interest in CoV biology pathogenesis (12, 22, 23, 34, 36). more recent discovery yet another human CoV, HCoV-NL63 (14, 45), also implicated disease, further emphasizes pathogenic potential CoVs stresses need for development new prophylactic therapeutic strategies. Among most conspicuous clinicopathological findings reported SARS protracted multiphasic course infection recurrence fever disease after initial apparent improvement consistent CD4+ CD8+ T-cell lymphopenia (4, 8, 36, 44, 56). this respect, there striking similarities lethal occurring cats. Feline infectious peritonitis (FIP) is progressive debilitating condition caused by FIP (FIPVs) (for review, see reference 9), virulence mutants spontaneously arising from apathogenic feline field strains (18, 35, 49). Typical widespread pyogranulomatous lesions, which occur various tissues organs, including lung, liver, spleen, omentum, brain (32, 50, 54). macrophages monocytes thought be key mechanism (40, 52). There ample evidence crucial involvement immune system. A profound depletion periphery lymphatic tissues, observed cats end-stage (16, 21), occurrence hypergammaglobulinemia (29, 50) indicative virus-induced dysregulation (20). humoral response against FIPV does not seem protective can fact lead “early death syndrome,” fulminating drastically shortened (31, Antibodies directed spike protein S, when present at subneutralizing titers, apparently opsonize virus enhance target cells via Fc receptor-mediated attachment (7, 19, 47). It commonly believed that control clearance primarily achieved through cell-mediated immunity (CMI) (17, 51). Here, we comprehensive study natural history immunobiology FIP, based upon longitudinal experiments performed highly virulent strain 79-1146. We show causes recurrent waves enhanced replication coinciding fever, weight loss, dramatic decline peripheral counts. Consistent notion CMI protective, detected FIPV-specific Th1 responses surviving animals S main antigen. model discussed cellular counteracted efficacy critically determines progression ultimate outcome infection.