OmniVira

Structure and receptor recognition of type-II feline infectious peritonitis virus spike glycoprotein.

Sheng Niu1 Yuyang Tian2 Linh Nguyen3 Chongzhi Bai2,4 Xiaohan Hou2 Dan Wang2 Ziqian Niu2 Zhimin Liu2 Jianle Ren2 Wentao Li5 Qihui Wang2,3 Wen-Xia Tian6 Junqing Sun7,8,9,10 George Fu Gao2,3
Affiliations 10 institutions
  1. Shanxi Key Laboratory of Animal Disease Research, Prevention and Control, College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China. [email protected].
  2. Shanxi Key Laboratory of Animal Disease Research, Prevention and Control, College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China.
  3. CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
  4. Central Laboratory, Shanxi Province Hospital of Traditional Chinese Medicine, Taiyuan, China.
  5. National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
  6. Shanxi Key Laboratory of Animal Disease Research, Prevention and Control, College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China. [email protected].
  7. Shanxi Key Laboratory of Animal Disease Research, Prevention and Control, College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China. [email protected].
  8. CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China. [email protected].
  9. Innovative Vaccine and Immunotherapy Research Center, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. [email protected].
  10. Transvascular Implantation Devices Research Institute, Hangzhou, China. [email protected].
PMID42420488 DOI10.1038/s44318-026-00849-2 Year2026 Journal The EMBO journal EMBO J Languageeng Statusaheadofprint

Abstract

Type-II feline infectious peritonitis virus (FIPV-II) is a lethal alphacoronavirus, whose high homology with the human coronavirus CCoV-HuPn-2018 carries the risk of potential zoonotic FIPV-II transmission to humans. FIPV-II infects felids using cat aminopeptidase N (cAPN) as its cell-entry receptor, but the molecular details remain unclear. Here, we resolved cryo-electron microscopy (cryo-EM) structures of the spike (S) trimer of a representative FIPV-II strain 79-1146 (FIPV-1146), and of its complex with cAPN. The reconstructions reveal structural transitions of the S protein between the "standing" and "lying" receptor-binding domain (RBD) conformation upon complex formation with cAPN in its open conformation. Structural and mutational analyses revealed that the cAPN residues R378, D751 and R779, as well as the N748-linked glycan are essential for high-affinity RBD engagement. Cross-species analysis demonstrated narrow tropism of FIPV-1146, limited to felids and canids. Introducing the N595K and Q596R substitutions found in transmissible gastroenteritis virus (TGEV) into the FIPV-1146 RBD expands its binding capacity to APNs from pig, bovine, horse and giant panda. These findings provide insights into the entry mechanism and zoonotic constraints of FIPV-II, with potential relevance for antiviral strategies against coronaviruses.

Supporting text Virus Host Location

Evidence records

4 total
Experimental Infection
2 records · 1 evidence types
Evidence type Host Range Experiment
2 records
OVE11737 Host Range Experiment
Key finding

Introducing N595K and Q596R into the FIPV-1146 RBD expanded binding to APNs from pig, bovine, horse, and giant panda.

Virus
FIPV-1146 RBD N595K+Q596R
Host
pig Sus scrofa Experimental system domestic cattle Bos taurus Experimental system horse Equus caballus Experimental system giant panda Ailuropoda melanoleuca Experimental system
Location
Not specified
Supporting text

Introducing the N595K and Q596R substitutions found in transmissible gastroenteritis virus (TGEV) into the FIPV-1146 RBD expands its binding capacity to APNs from pig, bovine, horse and giant panda.

Method
mutational analysis | receptor-binding assay | cross-species analysis
Experimental system
cross-species receptor-binding host-range assay (APN-based)
OVE11736 Host Range Experiment
Key finding

FIPV-1146 shows a narrow host-range, binding only to APNs from felids and canids under cross-species testing.

Virus
FIPV-1146
Host
cat family Felidae Experimental system dog, coyote, wolf, fox Canidae Experimental system
Location
Not specified
Supporting text

Cross-species analysis demonstrated narrow tropism of FIPV-1146, limited to felids and canids.

Method
cross-species analysis | receptor-binding assay
Experimental system
cross-species receptor-binding host-range assay (APN-based)
Functional Mechanism
2 records · 2 evidence types
Evidence type Receptor Usage
1 records
OVE11735 Receptor Usage
Key finding

Type-II feline infectious peritonitis virus (FIPV-1146) uses cat aminopeptidase N (cAPN) as its entry receptor, with specific cAPN residues and an N748-linked glycan essential for high-affinity spike RBD engagement.

Virus
FIPV-1146 Type-II feline infectious peritonitis virus FIPV-II
Host
domestic cat Felis catus Experimental system
Location
Not specified
Supporting text

Here, we resolved cryo-electron microscopy (cryo-EM) structures of the spike (S) trimer of a representative FIPV-II strain 79-1146 (FIPV-1146), and of its complex with cAPN... Structural and mutational analyses revealed that the cAPN residues R378, D751 and R779, as well as the N748-linked glycan are essential for high-affinity RBD engagement.

Method
cryo-electron microscopy structure of spike–cAPN complex | structural analysis | mutational analysis
Receptors
cat aminopeptidase N | cAPN
Host factors
N748-linked glycan on cAPN | R378 on cAPN | D751 on cAPN | R779 on cAPN
Evidence type Molecular Adaptation
1 records
OVE11738 Molecular Adaptation
Key finding

Introducing N595K and Q596R into the FIPV-1146 RBD broadens APN receptor binding to pig, bovine, horse, and giant panda APNs.

Virus
FIPV-1146 Transmissible gastroenteritis virus
Host
Not specified
Location
Not specified
Supporting text

Introducing the N595K and Q596R substitutions found in transmissible gastroenteritis virus (TGEV) into the FIPV-1146 RBD expands its binding capacity to APNs from pig, bovine, horse and giant panda.

Genes or proteins
RBD | spike (S)
Receptors
APN
Mutations
N595K | Q596R
Mechanism types
receptor binding | host-range expansion | host entry