Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

A Receptor Integrin β1 Promotes Infection of Avian Metapneumovirus Subgroup C by Recognizing Viral Fusion Protein RSD Motif

Yongqiu Cui
ORCID logo ,
Siting Li
,
Weiyin Xu
,
Yeqiu Li
,
Jiali Xie
,
Dedong Wang
,
Jinshuo Guo
,
Jianwei Zhou
,
Xufei Feng
,
Lei Hou
,
JUE LIU
*
Version 1 : Received: 15 December 2023 / Approved: 18 December 2023 / Online: 18 December 2023 (10:19:05 CET)

A peer-reviewed article of this Preprint also exists.

Cui, Y.; Li, S.; Xu, W.; Li, Y.; Xie, J.; Wang, D.; Guo, J.; Zhou, J.; Feng, X.; Hou, L.; Liu, J. A Receptor Integrin β1 Promotes Infection of Avian Metapneumovirus Subgroup C by Recognizing a Viral Fusion Protein RSD Motif. Int. J. Mol. Sci. 2024, 25, 829. Cui, Y.; Li, S.; Xu, W.; Li, Y.; Xie, J.; Wang, D.; Guo, J.; Zhou, J.; Feng, X.; Hou, L.; Liu, J. A Receptor Integrin β1 Promotes Infection of Avian Metapneumovirus Subgroup C by Recognizing a Viral Fusion Protein RSD Motif. Int. J. Mol. Sci. 2024, 25, 829.

Abstract

Avian metapneumovirus subgroup C (aMPV/C) causes respiratory diseases and egg dropping in chickens and turkeys, resulting in severe economic losses to the poultry industry worldwide. Integrin β1 (ITGB1), a transmembrane cell adhesion molecule, is present in various cells and mediates numerous viral infections. Herein, we demonstrate that ITGB1 is essential for aMPV/C infection in cultured DF-1 cells, as evidenced by the inhibition of viral binding by EDTA blockade, Arg-Ser-Asp (RSD) peptide, monoclonal antibody against ITGB1, and ITGB1 short interfering (si) RNA knockdown in cultured DF-1 cells. Simulation of the binding process between the aMPV/C fusion (F) protein and avian-derived ITGB1 using molecular dynamics showed that ITGB1 may be a host-factor for benefiting aMPV/C attachment or internalization. Transient expression of avian ITGB1 rendered porcine and feline non-permissive cells (DQ cells and CRFK cells, respectively) susceptible to aMPV/C infection. Replication kinetic of aMPV/C in siRNA-knockdown cells revealed that ITGB1 plays an important role in aMPV/C infection at the early stage (attachment and internalization). aMPV/C was also able to infect efficiently human non-small cell lung cancer (A549) cells. This may be due to a consequence of the similar structures of both metapneumovirus F protein-specific motifs (RSD for aMPV/C and RGD for human metapneumovirus) recognized by ITGB1. Overexpression of avian-derived ITGB1 and human-derived ITGB1 in A549 cells enhanced aMPV/C infectivity. Taken together, this study demonstrated that ITGB1 acts as an essential receptor for aMPV/C attachment and internalization into host cells in which facilitates aMPV/C infection.

Keywords

Avian metapneumovirus subgroup C; fusion protein; integrin β1; viral entry; avian and human cells

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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