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Evolving insights into FIP virulence

Terada Y, Shiozaki Y, Shimoda H, et al. Feline infectious peritonitis virus with a large deletion in the 5′-terminal region of the spike gene retains its virulence for cats. The Journal of general virology. 2012; 93: 1930-4. 

The acquisition of macrophage tropism appears to be an essential step in the transformation of feline enteric corona virus (FECV) to feline infectious peritonitis virus (FIPV).This is a transformation from a largely non-pathogenic and localized enterocyte pathogen to a highly virulent and systemic monocyte/macrophage pathogen. Therefore, determining the critical genetic mutation(s) leading a change in tropism is required for understanding the pathogenic phenomena of feline coronavirus (FCoV) infections. Although various viral proteins such as 3c and 7b have been considered to be involved in the transformation, the spike (S) protein may also play a role in a switch toward macrophage tropism and enhanced virulence. 

In coronaviruses, the S protein functions in cell entry and is responsible for receptor attachment and membrane fusion. While the receptor-binding site is located in the N-terminal part of the protein, fusion is mediated by its membrane proximal part. Surprisingly, previous studies have suggested virulence mutation(s) in the S protein occur in the membrane-proximal domain of the protein and not in the N-terminal region. 

In the present study, a type I FCoV strain, C3663, was found to have a large deletion of 735 bp within the gene encoding for the S protein, resulting in an estimated 245 amino acid loss in the N-terminal region of the protein. FIP developed in three out of four cats that were infected with strain C3663, suggesting that the 5’-terminal region of the S gene is not essential for pathogenic transformation. If the S protein is indeed involved in the transformation and development of FIP, then this result is consistent with the localization of the determinant for macrophage tropism lying in the domain responsible for membrane fusion suggesting a role for fusion function rather than for receptor binding. [GO]

See also: Rottier PJ, Nakamura K, Schellen P, Volders H and Haijema BJ. Acquisition of macrophage tropism during the pathogenesis of feline infectious peritonitis is determined by mutations in the feline coronavirus spike protein. J Virol. 2005; 79: 14122-30.