Identification of within-host deletions in domain 0 of the spike gene of highly pathogenic feline coronavirus type 2 from the United States

Feline coronavirus (FCoV) is known to gain pathogenicity within-host to cause the lethal disease feline infectious peritonitis (FIP). Most FIP cases are caused by viruses in genotype 1 (FCoV-1) via an internal mutation in the spike gene. However, genotype 2 (FCoV-2) has risen to prominence based on the emergence of FCoV-23, a highly pathogenic novel variant from Cyprus that has a deletion in the N-terminus (domain 0) of spike. Here, we conducted a retrospective molecular study of FCoV-2 detected in three cats in the U.S. during 2013 and 2016. Whole-genome sequencing revealed that the two cats exhibiting long-term signs each had an FCoV-2 with a distinct deletion in domain 0 of spike in all examined tissues. The epidemiologically-linked cat displaying signs for a short duration had an FCoV-2 with an intact spike. Our results suggest that this "internal deletion" in the spike gene is a biomarker of highly pathogenic FCoV-2. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=160 SRC="FIGDIR/small/664542v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@1d10d9eorg.highwire.dtl.DTLVardef@1d53c7forg.highwire.dtl.DTLVardef@76ef35org.highwire.dtl.DTLVardef@528d1f_HPS_FORMAT_FIGEXP M_FIG C_FIG