M135R is a novel cell surface virulence factor of myxoma virus.
Myxoma virus (MV) encodes a cell surface protein (M135R) that is predicted to mimic the host alpha/beta interferon receptor (IFN-alpha/beta-R) and thus prevent IFN-alpha/beta from triggering a host antiviral response. This prediction is based on sequence similarity to B18R, the viral IFN-alpha/beta-R from vaccinia virus (VV), which has been demonstrated to bind and inhibit type I interferons. However, M135R is only half the size of VV B18R. All other poxvirus-encoded IFN-alpha/beta-R homologs align only to the amino-terminal half of M135R. Peptide antibodies raised against M135R were used for immunoblotting and immunofluorescence and indicate that M135R is expressed as an early gene and that the product is a cell surface N-linked glycoprotein that is not secreted. In contrast to the predicted properties of M135R as an inhibitor of type I interferon, all binding and inhibition assays designed to demonstrate whether M135R can interact with IFN-alpha/beta have been negative. However, pathogenesis studies with a targeted M135-knockout MV construct (vMyx135KO) indicate that the deletion of M135R severely attenuates MV pathogenesis in the European rabbit. We propose that M135R is an important immunomodulatory virulence factor for myxomatosis but that the target immune ligand is not from the predicted type I interferon family and remains to be identified.
Barrett
John W
JW
Biotherapeutics Research Group, Robarts Research Institute and Department of Microbiology and Immunology, University of Western Ontario, 1400 Western Road, Room 126, London, ON N6G 2V4, Canada.
Sypula
Joanna
J
Wang
Fuan
F
Alston
Lindsay R
LR
Shao
Zhuhong
Z
Gao
Xiujuan
X
Irvine
Timothy S
TS
McFadden
Grant
G
D000595:Amino Acid Sequence; D000818:Animals; D005455:Fluorescent Antibody Technique; D015151:Immunoblotting; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009233:Myxoma virus / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology; D009234:Myxomatosis, Infectious / Q000821:virology; D011817:Rabbits; D053633:Receptor, Interferon alpha-beta / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D016415:Sequence Alignment; D014616:Vaccinia virus / Q000378:metabolism; D014764:Viral Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D037521:Virulence Factors / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D014779:Virus Replication
D008565:Membrane Proteins; D014764:Viral Proteins; D037521:Virulence Factors; D053633:Receptor, Interferon alpha-beta