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

Abstract

We describe the natural history, viral dynamics, and immunobiology of feline infectious peritonitis (FIP), a highly lethal coronavirus infection. A severe recurrent infection developed, typified by viral persistence and acute lymphopenia, with waves of enhanced viral replication coinciding with fever, weight loss, and depletion of CD4؉ and CD8 ؉ T cells. Our combined observations suggest a model for FIP pathogenesis in which virus-induced T-cell depletion and the antiviral T-cell response are opposing forces and in which the efficacy of early T-cell responses critically determines the outcome of the infection. Rising amounts of viral RNA in the blood, consistently seen in animals with end-stage FIP, indicate that progression to fatal disease is the direct consequence of a loss of immune control, resulting in unchecked viral replication. The pathogenic phenomena described here likely bear relevance to other severe coronavirus infections, in particular severe acute respiratory syndrome, for which multiphasic disease progression and acute T-cell lymphopenia have also been reported. Experimental FIP presents a relevant, safe, and well-defined model to study coronavirus-mediated immunosuppression and should provide an attractive and convenient system for in vivo testing of anticoronaviral drugs.

Clinical and laboratory features of cats with feline infectious peritonitis – a retrospective study of 231 confirmed cases (2000–2010)

“…16,17,[45][46][47] Whereas Sparkes et al observed no significant difference in the lymphocyte count of cats with effusion vs those without effusion, 19 the present study documented lymphopenia significantly more often in cats with effusion (78/139; 56.1%). Only 26.8% (11/41) of cats without effusion had a reduced lymphocyte count.…”

Feline infectious peritonitis: insights into feline coronavirus pathobiogenesis and epidemiology based on genetic analysis of the viral 3c gene

“…FIPV) (re)activates immune mechanisms that lead to viral clearance from the gut. The severe immune dysregulation and collapse of key effectors of the immune system in cats with end-stage FIP (de Groot-Mijnes et al, 2005;Haagmans et al, 1996) might then create an opportunity for FECVs circulating in surrounding healthy carriers to cause the superinfections that we apparently observe in a fraction of the animals.…”

“…FIPV) (re)activates immune mechanisms that lead to viral clearance from the gut. The severe immune dysregulation and collapse of key effectors of the immune system in cats with end-stage FIP (de Groot-Mijnes et al, 2005;Haagmans et al, 1996) might then create an opportunity for FECVs circulating in surrounding healthy carriers to cause the superinfections that we apparently observe in a fraction of the animals.In view of its supposed role in the pathogenesis of FIP, the aim of the present study was to sequence and compare the Vennema et al, 1998) and with the internal mutation theory. Our key observation, however, is that the viruses replicating in the gut invariably had an intact 3c gene, whereas those replicating outside the gut mostly did not.…”

First molecular identification of ‘ Candidatus Mycoplasma haemominutum’ from a cat with fatal haemolytic anaemia in Hungary

“…The development of distinct anaemia in 'Candidatus M. haemominutum' infected cats has also been described with concomitant feline retroviral (FeLV, FIV) infections (George et al, 2002) or other deprived conditions (De Lorimier and Messick, 2004). Here PCR results were negative for FeLV, FIV and FCoV which may be immunosuppressive (Willis, 2000;De Groot-Mijnes et al, 2005) and thus may aggravate the manifestation of diseases. The assays applied here to detect FeLV or FIV have been shown to be highly sensitive, and they also detect proviraemia, therefore an infection of the cat with these viruses is unlikely.…”