Genetic determinants of pathogenesis by feline infectious peritonitis virus

Feline infectious peritonitis (FIP) is a fatal, immune-augmented, and progressive viral disease of cats associated with feline coronavirus (FCoV). Viral genetic determinants specifically associated with FIPV pathogenesis have not yet been discovered. Viral gene signatures in the spike, non-structural protein 3c, and membrane of the coronavirus genome have been shown to often correlate with disease manifestation. An "in vivo mutation transition hypothesis" is widely accepted and postulates that de novo virus mutation occurs in vivo giving rise to virulence. The existence of "distinct circulating avirulent and virulent strains" is an alternative hypothesis of viral pathogenesis. It may be possible that viral dynamics from both hypotheses are at play in the occurrence of FIP. Epidemiologic data suggests that the genetic background of the cat contributes to the manifestation of FIP. Further studies exploring both viral and host genetic determinants of disease in FIP offer specific opportunities for the management of this disease.     

Treatment of cats with feline infectious peritonitis

Feline infectious peritonitis (FIP) infection resulting in clinical signs is invariably fatal despite clinical intervention. As FIP is an immune-mediated disease, treatment is mainly aimed at controlling the immune response triggered by the infection with the feline coronavirus (FCoV). Immune suppressive drugs such as prednisone or cyclophosphamide may slow disease progression but do not produce a cure. In nearly every published case report of attempted therapy for clinical FIP, glucocorticoids have been used; there are, however, no controlled studies that evaluate the effect of glucocorticoids as a therapy for FIP. Some veterinarians prescribe immune modulators to treat cats with FIP with no documented controlled evidence of efficacy. It has been suggested that these agents may benefit infected animals by restoring compromised immune function, thereby allowing the patient to control viral burden and recover from clinical signs. However, a non-specific stimulation of the immune system may be contraindicated as clinical signs develop and progress as a result of an immune-mediated response to the mutated FCoV.     

Enhanced platelet reactivity in cats experimentally infected with feline infectious peritonitis virus

Platelet function was evaluated in six specific-pathogen-free cats prior to and following intraperitoneal inoculation with feline infectious peritonitis virus (FIPV). By 4 days post-inoculation, platelet samples from five of six cats responded with irreversible platelet aggregation to threshold concentrations of adenosine diphosphate (ADP). This was accompanied by enhanced platelet 14C-serotonin release (greater than 10%) in two cats. Compared to one of six baseline samples, five of five post-inoculation samples exhibited microaggregate formation in response to 20 microM epinephrine. Enhanced platelet 14C-serotonin release did not accompany these responses. Enhanced platelet responses to ADP and epinephrine were also observed on day 11 post-inoculation and day 16 (when one cat died) or 21 (the end of the study). Platelet 14C-serotonin release in response to 20 microM epinephrine increased markedly in three of five cats on day 21. Enhanced collagen-induced platelet responses were not demonstrated. Although the mechanism for the enhanced platelet responses observed on day 4 was unknown, a direct effect on the virus on platelets, mononuclear inflammatory cells, and endothelial cells must be considered.     

Demonstration of infectious bovine rhinotracheitis virus antigen in paraffin sections

Nine pregnant heifers were inoculated intravenously with infectious bovine rhinotracheitis virus (IBRV) in the sixth month of pregnancy. Tissues were collected from the fetus of a heifer killed 13 days postinoculation (PI), from fetuses of 6 heifers that aborted 16-27 days PI, and from mummified fetuses of 2 heifers that aborted 53 and 85 days PI, respectively. Control tissues were obtained from the fetus of a non-inoculated heifer that was killed in the seventh month of gestation. Tissues were fixed in 10% formalin, embedded in paraffin, and examined for viral antigen by immunohistochemistry, using biotinylated second antibody and alkaline phosphatase-labeled avidin-biotin complex. Antigen was detected in at least 1 tissue from the fetus of each inoculated heifer. Positive tissues included lung, liver, spleen, kidney, adrenal, and placenta. In several fetuses, antigen was identified in tissues from which virus was not isolated in cell culture. This appeared to occur when tissues had only a few small foci of infection or when tissues were severely autolyzed. The observation of viral antigen in tissues from mummified fetuses indicates that this technique may be useful in diagnostic laboratories to detect IBRV infection in tissues that are not suitable for virus isolation or for examination by the cryostat tissue section-fluorescent antibody technique.     

Potentiation of platelet responses in vitro by feline infectious peritonitis virus

The effect of feline infectious peritonitis virus (FIPV) on platelet aggregation and 14C-serotonin release induced by threshold levels of four agonists (adenosine diphosphate [ADP], collagen, arachidonic acid, and epinephrine) was examined in vitro in ten specific-pathogen-free cats. Purified suspensions of FIPV added to stirred platelet suspensions (virus to platelet ratio equal to 1:320) 1 minute prior to the addition of agonist potentiated the ADP-induced aggregation response by greater than 100% in seven cats. Platelet 14C-serotonin release was increased by greater than 100% in four cats. Collagen-induced platelet aggregation was enhanced in ten cats while collagen-induced 14C-serotonin release was enhanced in eight cats. Potentiation of arachidonic acid-induced platelet aggregation was observed in three cats, two of which demonstrated enhanced platelet 14C-serotonin release. Although epinephrine-induced platelet aggregation was enhanced in five cats, the samples displayed only fine microaggregates. Enhanced 14C-serotonin release from platelets in response to epinephrine was not demonstrated. Interaction with the outer platelet membrane and internalization of viral particles within the surface-connected open canalicular system were demonstrated by electron microscopy within 5 minutes of the addition of virus to platelet suspensions with or without added agonists. Decreasing the virus concentration by ten- or one hundred-fold abolished the potentiating effect observed previously, while increasing the concentration tenfold resulted in direct platelet activation in the absence of agonist.(ABSTRACT TRUNCATED AT 250 WORDS)     

Epigenetic transmission of feline infectious peritonitis

Feline Infectious Peritonitis (F.I.P.) was diagnosed in the kittens of two successive litters born to a female presumed also infected.At the same time, the two fathers and the other subjects of the cattery remained asymptomatic of F.I.P.The clinical observations, supported by electrophoretic data, suggest the possibility of a direct transmission of the disease by the mother to her offspring, either by the transplacentary pathway (epigenetic transmission) or via the milk.     

Detection of feline coronavirus antibody, feline immunodeficiency virus antibody, and feline leukemia virus antigen in ascites from cats with effusive feline infectious peritonitis

To investigate the usefulness of ascites as a material for viral tests in cats with effusive feline infectious peritonitis (FIP), we attempted to detect anti-feline coronavirus antibody, anti-feline immunodeficiency virus antibody, and feline leukemia virus antigen in ascites from 88 cats clinically suspected with effusive FIP. In each of these three viral tests, all cats positive for serum antibody/antigen were also positive for ascitic antibody/antigen, while cats negative for serum antibody/antigen were also negative for ascitic antibody/antigen. This finding indicates that ascites is useful for these viral tests.     

Cutaneous lesions associated with coronavirus-induced vasculitis in a cat with feline infectious peritonitis and concurrent feline immunodeficiency virus infection

This report describes a clinical case of feline infectious peritonitis (FIP) with multisystemic involvement, including multiple nodular cutaneous lesions, in a cat that was co-infected with feline coronavirus and feline immunodeficiency virus. The skin lesions were caused by a pyogranulomatous-necrotising dermal phlebitis and periphlebitis. Immunohistology demonstrated the presence of coronavirus antigen in macrophages within these lesions. The pathogenesis of FIP involves a viral associated, disseminated phlebitis and periphlebitis which can arise at many sites. Target organs frequently include the eyes, abdominal organs, pleural and peritoneal membranes, and central nervous tissues, but cutaneous lesions have not previously been reported.     

Pericardial effusion in a cat with feline infectious peritonitis

This case report describes the disease progression of a male cat with pericardial effusion. Clinical signs (dyspnea, lethargy, and weakness) started very acutely. The initial laboratory profile showed only an increase in alanine aminotransferase enzyme activity. Diagnostic imaging revealed pericardial effusion. Effusion analysis showed a Rivalta-positive, modified transudate. Detection of feline coronavirus antigen in macrophages was negative. General condition and laboratory parameters dramatically worsened within seven days. Therefore, the owners decided to euthanize the cat. Even if effusion variables are macroscopically and microscopically suspicious for FIP, a definitive diagnosis of FIP could only be made by histology (including immunhistochemical staining).     

Humoral immune responses of cats to feline infectious peritonitis virus infection.

Immunoperoxidase antibody (IPA) method as a titrating method of feline infectious peritonitis (FIP) virus (FIPV) was developed for titrating antibody to FIPV (IPA-titer). By this method the immune responses of the cats that had been infected with FIPV, were traced. The infected cats could be grouped into three types by their immune response to FIPV and clinical appearances. Type I cats lived for a long time, formed a major group among infected cats, had 160 to 1 x 10(4) IPA-titers, and showed healthy appearances without any changes both on autopsy and histopathologically. From among type I cats, type II cats appeared sporadically with rapid elevation of IPA titers to 3.2 x 10(5) and showing clinical signs of FIP, and died. Type III cats lived healthily for a long time with gradual elevation of IPA-titers to a plateau of about 1 x 10(5), then showed neuronal disorder of hind leg paralysis with the descending IPA-titers to 2 x 10(4), and died. Thus, typical FIP appeared as a hyper-immune disease. Other related problems are discussed.