Modulation of Early Host Innate Immune Response by an Avipox Vaccine Virus’ Lateral Body Protein

Biomedicines

SusannaR. Bidgood¹  Jason Mercer¹  David Albrecht¹  JemimaJ. Burden¹  EfstathiosS. Giotis²  RebeccaC. Robey²  MichaelA. Skinner²  StephenM. Laidlaw² 

[1] Medical Research Council-Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK;Section of Virology, School of Medicine, St Mary’s Campus, Imperial College, London W2 1PG, UK;

关键词: fowlpox virus;    interferon;    lateral bodies;    nuclear localisation signal;    microarrays;   

DOI  :  10.3390/biomedicines8120634

来源: DOAJ

【 摘 要 】

The avian pathogen fowlpox virus (FWPV) has been successfully used as a vaccine vector in poultry and humans, but relatively little is known about its ability to modulate host antiviral immune responses in these hosts, which are replication-permissive and nonpermissive, respectively. FWPV is highly resistant to avian type I interferon (IFN) and able to completely block the host IFN-response. Microarray screening of host IFN-regulated gene expression in cells infected with 59 different, nonessential FWPV gene knockout mutants revealed that FPV184 confers immunomodulatory capacity. We report that the FPV184-knockout virus (FWPVΔ184) induces the cellular IFN response as early as 2 h postinfection. The wild-type, uninduced phenotype can be rescued by transient expression of FPV184 in FWPVΔ184-infected cells. Ectopic expression of FPV184 inhibited polyI:C activation of the chicken IFN-β promoter and IFN-α activation of the chicken Mx1 promoter. Confocal and correlative super-resolution light and electron microscopy demonstrated that FPV184 has a functional nuclear localisation signal domain and is packaged in the lateral bodies of the virions. Taken together, these results provide a paradigm for a late poxvirus structural protein packaged in the lateral bodies, capable of suppressing IFN induction early during the next round of infection.

【 授权许可】

Unknown