Type I feline coronavirus spike glycoprotein fails to recognize aminopeptidase N as a functional receptor on feline cell lines

Abstract

There are two types of feline coronaviruses that can be distinguished by serology and sequence analysis. Type I viruses, which are prevalent in the field but are difficult to isolate and propagate in cell culture, and type II viruses, which are less prevalent but replicate well in cell culture. An important determinant of coronavirus infection, in vivo and in cell culture, is the interaction of the virus surface glycoprotein with a cellular receptor. It is generally accepted that feline aminopeptidase N can act as a receptor for the attachment and entry of type II strains, and it has been proposed that the same molecule acts as a receptor for type I viruses. However, the experimental data are inconclusive. The aim of the studies reported here was to provide evidence for or against the involvement of feline aminopeptidase N as a receptor for type I feline coronaviruses. Our approach was to produce retroviral pseudotypes that bear the type I or type II feline coronavirus surface glycoprotein and to screen a range of feline cell lines for the expression of a functional receptor for attachment and entry. Our results show that type I feline coronavirus surface glycoprotein fails to recognize feline aminopeptidase N as a functional receptor on three continuous feline cell lines. This suggests that feline aminopeptidase N is not a receptor for type I feline coronaviruses. Our results also indicate that it should be possible to use retroviral pseudotypes to identify and characterize the cellular receptor for type I feline coronaviruses.

Feline Coronaviruses

“…This hypothesis was supported by experiments using pseudotyped retroviruses containing the spike protein of FCoV serotypes I and II, respectively, to transduce different continuous cat cell lines. The data obtained in this study provided evidence that serotype I spike fails to recognize fAPN as a receptor for attachment and entry, suggesting that fAPN is not a functional receptor for serotype I FCoVs (Dye et al, 2007). In line with this, recombinant serotype I FCoVs generated by reverse genetics and expressing serotype I and serotype II S proteins, respectively, were used to demonstrate that the S protein alone is responsible for the different receptor usage of serotype I and serotype II FCoVs (Tekes et al, 2010).…”

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

“…This receptor was first shown to be the key FCoV receptor by Tresnan et al [64] in 1996, where it was shown to be a common receptor for many alphacoronaviruses, including the type I strain UCD-1. However, subsequent follow up studies have shown that this receptor appears to be suitable for FCoV type II, but not for type I [74,78]. As such, the primary receptor for serotype I viruses remains to be identified.…”

Differential effect of cholesterol on type I and II feline coronavirus infection

“…Although recombinant type I FCoV has recently been prepared by reverse genetics [30], studies on type I FCoV have not progressed. Differences have been identified in the following events between types I and II FCoV: replicative ability in cell lines and monocytes/macrophages [29], the amino acid sequence and immunogenicity of the S protein [10,19], and the virus receptor used to enter cells [4,8]. However, differences in other events remain unclear, and the virus receptor for type I FCoV has not yet been identified.…”