Distinct mutation in the feline coronavirus spike protein cleavage activation site in a cat with feline infectious peritonitis-associated meningoencephalomyelitis

André, Nicole M; Cossic, Brieuc; Davies, Emma; Miller, Andrew D; Whittaker, Gary R

Feline infectious peritonitis (FIP) is caused by feline coronavirus (FCoV) and is widely considered to be one of the most significant infectious diseases to affect the feline population. [1] [2] [3] It is the most common infectious disease of the central nervous system (CNS) of cats. 4 FCoVs have been reported to exist as two distinct serotypes: type I (more common) and type II viruses, 5 each with distinct biological properties. 5, 6 Both FCoV serotypes have distinct 'biotypes'. These are typically classified as either feline enteric coronavirus (FECV) or feline infectious peritonitis virus (FIPV), with the biotypes differing based on the severity of infection in cats. [7] [8] [9] Infection with FCoV is common, especially in highdensity housing situations such as animal shelters and breeding facilities. 10 The FECV biotype transmits readily and causes only a mild infection, with transmission occurring via fecal-oral and possibly other routes. 7, 11 If the viral infection worsens and becomes systemic (typically infecting macrophages), then the virus is classified as the FIPV biotype. 8 Such viruses are believed to contain an 'internal mutation' that accounts for the altered tropism, although the nature of this mutation is not well understood. 12 Clinical signs associated with the FIPV biotype can be quite variable and non-specific, and can include fever, lethargy, anorexia, pica, vomiting and diarrhea. 13 These clinical signs can be present in either the 'wet', 'dry' or 'mixed' presentations. 14 The wet form of FIP is characterized by an effusion in the abdominal and/or thoracic or pericardial cavities, and the 'dry' form by the presence of pyogranulomatous lesions. The 'mixed' form may present with an array of clinical signs. Most commonly, neurologic clinical signs are associated with the 'dry' form but can occur with all presentations and may be the sole clinical sign observed. 12, 13 Clinical features of neurologic FIP can include, but are not limited to, ataxia, head tremors, seizures and/or paresis. 12, 13, 15 Ocular lesions may be present with or without lesions in the CNS. FIP-associated pathologic changes to the CNS include meningitis, encephalitis, ependymitis and choroid plexitis, often with concurrent vasculitis. 12,13 FIP presenting with predominantly neurologic clinical signs provides a diagnostic challenge and definitive ante-mortem diagnosis is difficult. MRI has been identified as a sensitive method of diagnosis in conjunction with clinical signs and cerebrospinal fluid analysis results such as elevated protein levels and neutrophilic pleocytosis. 16 However, such findings are still not specific to FIP and may be financially prohibitive. FIP may also be considered a diagnosis of exclusion, following evaluation of clinical signs, history and physical examination findings and biochemical values. 12, 13 This case report describes a cat with neurologic FIP that progressed over several months. The observations and findings obtained in this case provide support that FIP can present predominantly in the CNS. When molecular techniques are applied to the virus, a propensity for certain mutations can be associated with specific clinical presentations or pathological changes.