Bank-Wolf BR, Stallkamp I, Wiese S, et al. Mutations of 3c and spike protein genes correlate with the occurrence of feline infectious peritonitis. Vet Microbiol. 2014 Oct 10; 173(3-4):177-188.
Feline coronavirus (FCoV) has a worldwide distribution and infect all members of the Felidae family. It has been estimated that ~ 80-90% of cats in catteries and ~ 10-50% of cats in single cat households are seropositive for FCoV, meaning many if not most cats have been infected (or exposed) to the virus some time in their lives. About ~ 5-10% of FCoV infected cats sporadically develop feline infectious peritonitis (FIP), mostly within the first 2 years of their lives. In fact, FIP represents the leading viral cause of death in domestic cats. It has previously been demonstrated that feline enteric corona virus (FECV), which has a low pathogenic potential, and FIP, which is almost 100% lethal, are virulence variances of the same virus. Therefore, identifying the genetic changes or mutations that distinguish between FECV and FIP would be necessary in order to provide better diagnostics or treatment for FIP, which remain problematic to date.
Researchers at the Justus-Liebig-Universität Giessen, Giessen, Germany amplified, cloned and sequenced genes encoding accessory proteins 3a, 3b, 3c, 7a and 7b, the S2 domain of the spike (S) protein gene and the membrane (M) protein gene of FIPV and FECV samples. The function of the accessory proteins is unknown but speculated to be involved in conferring viral virulence. The spike (S) protein is involved in host cell recognition, binding and fusion while the membrane protein is involved in virion budding and cell-mediated host immunity. Feces and/or abdominal fluid samples were obtained from 19 cats with FIP and 20 FECV-infected healthy cats. Nucleotide sequence comparisons revealed that 3c genes of cats with FIP where heavily affected by deletions and point mutations compared to cats infected with FECV. Two abdominal fluid derived samples of cats with FIP displayed no alterations of the 3c gene but had mutations in the S2 domain of the spike (S) protein gene. Moreover, changes in 3c were often accompanied by mutations in S2. In addition, in this study fecal samples of healthy cats were never affected with 3c mutations. Similarly 3c gene from fecal samples of cats with FIP was mostly intact and showed only in a few cases the same mutations as found in the abdominal fluid. No mutations were displayed in the genes encoding 3a, 3b, 7a and 7b that could be linked to FCoV biotype difference.
In summary, results from this study support the involvement of mutations in 3c and spike (S) genes in the biotype switch from FECV to FIPV. In addition, the data suggests that the involvement of other investigated genes (3a, 3b, 7a, 7b and M) role in FIP development is negligible. The data further support the “internal mutation theory” rather than the “circulating virulent/avirulent FCoV” hypothesis. [GO]
Licitra BN, Millet JK, Regan AD, et al. Mutation in spike protein cleavage site and pathogenesis of feline coronavirus. Emerg Infect Dis. 2013 Jul;19(7):1066-1073.
Chang HW, Egberink HF, Halpin R, et al. Spike protein fusion peptide and feline coronavirus virulence. Emerg Infect Dis 2012, 18:1089–1095.