FELINE AMINOPEPTIDASE-N SERVES AS A RECEPTOR FOR FELINE, CANINE, PORCINE, AND HUMAN CORONAVIRUSES IN SEROGROUP-I

Two members of coronavirus serogroup I, human respiratory coronavirus HCV-229E and porcine transmissible gastroenteritis virus (TGEV), use a minopeptidase N (APN) as their cellular receptors. These viruses show marked species specificity in receptor utilization, as HCV-229E can ut ilize human but not porcine APN, while TGEV can utilize porcine but no t human APN. To determine whether feline APN could serve as a receptor for two feline coronaviruses in serogroup I, feline infectious perito nitis virus (FIPV) and feline enteric coronavirus (FeCV), we cloned th e cDNA encoding feline APN (fAPN) by PCR from cDNA isolated from a fel ine cell line and stably expressed it in FIPV- and FeCV-resistant mous e and hamster cells. The predicted amino acid sequence of fAPN shows 7 8 and 77% identity with human and porcine APN, respectively, When inoc ulated with either of two biologically different strains of FIPV or wi th FeCV, fAPN-transfected mouse and hamster cells became infected and viral antigens developed in the cytoplasm, Infectious FIPV was release d from hamster cells stably transfected with fAPN, The fAPN-transfecte d mouse and hamster cells were challenged with other coronaviruses in serogroup I including canine coronavirus, porcine coronavirus TGEV, an d human coronavirus HCV-229E. In addition to serving as a receptor for the feline coronaviruses, fAPN also served as a functional receptor f or each of these serogroup I coronaviruses as shown by development of viral antigens in the cytoplasm of infected mouse or hamster cells sta bly transfected with fAPN, In contrast, fAPN did not serve as a functi onal receptor for mouse hepatitis virus (MHV-A59), which is in serogro up II and utilizes mouse biliary glycoprotein receptors unrelated to A PN, Thus, fAPN serves as a receptor for a much broader range of group I coronaviruses than human and porcine APNs. The human, porcine, and c anine coronaviruses in serogroup I that are able to use fAPN as a rece ptor have previously been shown to infect cats without causing disease , Therefore, host factors in addition to receptor specificity apparent ly affect the virulence and transmissibility of nonfeline serogroup I coronaviruses in the cat.