1. Academic Validation
  2. VP2 mediates the release of the feline calicivirus RNA genome by puncturing the endosome membrane of infected cells

VP2 mediates the release of the feline calicivirus RNA genome by puncturing the endosome membrane of infected cells

  • J Virol. 2024 Apr 9:e0035024. doi: 10.1128/jvi.00350-24.
Weiyao Sun 1 Ming Wang 1 Zhibin Shi 1 Pengfei Wang 1 Jinhui Wang 1 Bingchen Du 1 Shida Wang 1 Zhenzhao Sun 1 Zaisi Liu 1 Lili Wei 1 Decheng Yang 1 Xijun He 1 Jingfei Wang 1
Affiliations

Affiliation

  • 1 State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
Abstract

Feline calicivirus (FCV) is one of the few members of the Caliciviridae family that grows well in cell lines and, therefore, serves as a surrogate to study the biology of other viruses in the family. Conley et al. (14) demonstrated that upon the receptor engagement to the capsid, FCV VP2 forms a portal-like assembly, which might provide a channel for RNA release. However, the process of calicivirus RNA release is not yet fully understood. Our findings suggest that the separation of the FCV capsid from its genome RNA (gRNA) occurs rapidly in the early endosomes of infected cells. Using a Liposome model decorated with the FCV cell receptor fJAM-A, we demonstrate that FCV releases its gRNA into the liposomes by penetrating membranes under low pH conditions. Furthermore, we found that VP2, which is rich in hydrophobic residues at its N-terminus, functions as the pore-forming protein. When we substituted the VP2 N-terminal hydrophobic residues, the gRNA release efficacy of the FCV mutants decreased. In conclusion, our results suggest that in the acidic environment of early endosomes, FCV VP2 functions as the pore-forming protein to mediate gRNA release into the cytoplasm of infected cells. This provides insight into the mechanism of calicivirus genome release.IMPORTANCEResearch on the biology and pathogenicity of certain caliciviruses, such as Norovirus and Sapovirus, is hindered by the lack of easy-to-use Cell Culture system. Feline calicivirus (FCV), which grows effectively in cell lines, is used as a substitute. At present, there is limited understanding of the genome release mechanism in caliciviruses. Our findings suggest that FCV uses VP2 to pierce the endosome membrane for genome release and provide new insights into the calicivirus gRNA release mechanism.

Keywords

VP2 protein; calicivirus; genome release; membrane penetration.

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