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Review
. 2020 Jan 10;12(1):83.
doi: 10.3390/v12010083.

A Tale of Two Viruses: The Distinct Spike Glycoproteins of Feline Coronaviruses

Javier A Jaimes  1 , Jean K Millet  2 , Alison E Stout  1 , Nicole M André  1 , Gary R Whittaker  1
Affiliations
Review

A Tale of Two Viruses: The Distinct Spike Glycoproteins of Feline Coronaviruses

Javier A Jaimes et al. Viruses. .

Abstract

Feline coronavirus (FCoV) is a complex viral agent that causes a variety of clinical manifestations in cats, commonly known as feline infectious peritonitis (FIP). It is recognized that FCoV can occur in two different serotypes. However, differences in the S protein are much more than serological or antigenic variants, resulting in the effective presence of two distinct viruses. Here, we review the distinct differences in the S proteins of these viruses, which are likely to translate into distinct biological outcomes. We introduce a new concept related to the non-taxonomical classification and differentiation among FCoVs by analyzing and comparing the genetic, structural, and functional characteristics of FCoV and the FCoV S protein among the two serotypes and FCoV biotypes. Based on our analysis, we suggest that our understanding of FIP needs to consider whether the presence of these two distinct viruses has implications in clinical settings.

Keywords: feline coronavirus; feline infectious peritonitis; genetic characterization; serotype; spike protein.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Diagram of the S gene flow within the Alphacoronavirus 1 species. In this schematic diagram the evolution of members of the Alphacoronavirus 1 species is summarized using a S gene-centric view. It is thought that clade A (serotype I) CCoV and FCoV share a common ancestor. A recombination event with an unknown coronavirus allowed the emergence of a clade B (serotype II) CCoV with a S protein distinct from clade A CCoV. Multiple independent recombination events led to the emergence of clade B (serotype II) FCoV and recombinant A/B (serotype I/II) CCoV. TGEV is believed to have emerged from clade B CCoV. Partial deletion of the N-terminal domain of the S protein of TGEV gave rise to PRCV.
Figure 2
Figure 2
The FCoV S gene and protein functional components. A schematic of the FCoV S gene (A) and the S protein (B left), the S1 domain or RBD forms the head of the protein, while the S2 domain (fusion domain) forms the stalk of the protein. Trimeric structure of the S protein of HCoV-NL63 (PDB # 5SZS) (B right). The structure of the transmembrane domain has not yet been solved. The two domains S1 (blue) and S2 (green), as well as the major functional components RBD (NTD and C-domain), FP (bright blue), HR1, HR2 and the transmembrane domain (TM) are noted.
Figure 3
Figure 3
Alignment of the S1/S2 region of FCoV I and FCoV II strains. Sequences corresponding to the S1/S2 region of three FCoV type I strains (FCoV-RM, FCoV-UU47 and FCoV-TN406) and three FCoV type II strains (FCoV-DF-2, FCoV-WSU-79-1683 and FCoV-WSU-79-1146) reported in GenBank, and 15 FCoV type I sequences from clinical samples reported in the European Nucleotide Archive were aligned using the Geneious Prime 2019 (v.2019.2.3) software package (supplementary information 1). A 16 amino acid insertion including the S1/S2 cleavage site (6 amino acid) and a 10 amino acid flanking region was only observed in type I strains. FCoV type I sample are partial sequences, amino acid nomenclature cannot be displayed.
Figure 4
Figure 4
In silico modeling of the S protein from FCoV I and FCoV II strains. In silico FCoV S models of three FCoV type I strains (FCoV-RM, FCoV-UU47 and FCoV-TN406) and three FCoV type II strains (FCoV-DF-2, FCoV-WSU-79-1683 and FCoV-WSU-79-1146) were built using Chimera (UCSF Chimera v. 1.13.1, University of California). The S1/S2 region (dashed squares) was magnified to better visualize the differences between the two serotypes. The 16 amino acid insertion corresponding to the S1/S2 site (bright blue) and the 10 amino acid flanking region (yellow) were predicted as a flexible loop only in the FCoV type I S models.
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