Myxoma virus M11L ORF encodes a protein for which cell surface localization is critical in manifestation of viral virulence

Kathryn A. Graham, Andrea Opgenorth, Chris Upton, Douglas McFadden

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Myxoma virus (MYX) induces extensive immunosuppression in infected rabbits and is associated with high levels of mortality. The virus encodes multiple gene products designed to circumvent the cellular immune response to the viral infection. Deletion analysis has shown that the M11L open reading frame (ORF) is an important virulence factor which downregulates leukocyte infiltration of MYX-induced tumors. To investigate the role of the M11 L protein in viral pathogenesis, we sequenced the MYX M11L ORF and showed that the sequence has motifs consistent with a 166-aa class III membrane-spanning molecule possessing a single transmembrane helix near the C-terminus and a 142-aa N-terminal extracellular domain that has six cysteine residues plus two consensus N-glycosylation sites. Transcription analysis indicates that M11 L is expressed as an early gene, and surface immunofluorescence studies with anti-M11L antibodies reveal that M11 L protein is transported to the infected cell surface. Immunoprecipitation analysis of an attenuated viral recombinant, vMYX-GF-ΔM11L, indicates that an M11 L variant protein with an altered C-terminus is synthesized at about 45% of wild type levels; however, it is not detectable on the cell surface, suggesting that proper M11L function requires localization at the infected cell membrane. We propose that M11L is a virulence factor whose function is to recognize an extracellular ligand essential for the cellular inflammatory response.

Original languageEnglish (US)
Pages (from-to)112-124
Number of pages13
JournalVirology
Volume191
Issue number1
DOIs
StatePublished - Jan 1 1992
Externally publishedYes

Fingerprint

Myxoma virus
Open Reading Frames
Virulence
Membrane Proteins
Virulence Factors
Viral Proteins
Virus Diseases
Glycosylation
Immunoprecipitation
Cellular Immunity
Immunosuppression
Genes
Fluorescent Antibody Technique
Cysteine
Anti-Idiotypic Antibodies
Proteins
Leukocytes
Down-Regulation
Cell Membrane
Rabbits

ASJC Scopus subject areas

  • Virology

Cite this

Myxoma virus M11L ORF encodes a protein for which cell surface localization is critical in manifestation of viral virulence. / Graham, Kathryn A.; Opgenorth, Andrea; Upton, Chris; McFadden, Douglas.

In: Virology, Vol. 191, No. 1, 01.01.1992, p. 112-124.

Research output: Contribution to journalArticle

Graham, Kathryn A. ; Opgenorth, Andrea ; Upton, Chris ; McFadden, Douglas. / Myxoma virus M11L ORF encodes a protein for which cell surface localization is critical in manifestation of viral virulence. In: Virology. 1992 ; Vol. 191, No. 1. pp. 112-124.
@article{4c5beb86d7264bc3a99ab04179549e90,
title = "Myxoma virus M11L ORF encodes a protein for which cell surface localization is critical in manifestation of viral virulence",
abstract = "Myxoma virus (MYX) induces extensive immunosuppression in infected rabbits and is associated with high levels of mortality. The virus encodes multiple gene products designed to circumvent the cellular immune response to the viral infection. Deletion analysis has shown that the M11L open reading frame (ORF) is an important virulence factor which downregulates leukocyte infiltration of MYX-induced tumors. To investigate the role of the M11 L protein in viral pathogenesis, we sequenced the MYX M11L ORF and showed that the sequence has motifs consistent with a 166-aa class III membrane-spanning molecule possessing a single transmembrane helix near the C-terminus and a 142-aa N-terminal extracellular domain that has six cysteine residues plus two consensus N-glycosylation sites. Transcription analysis indicates that M11 L is expressed as an early gene, and surface immunofluorescence studies with anti-M11L antibodies reveal that M11 L protein is transported to the infected cell surface. Immunoprecipitation analysis of an attenuated viral recombinant, vMYX-GF-ΔM11L, indicates that an M11 L variant protein with an altered C-terminus is synthesized at about 45{\%} of wild type levels; however, it is not detectable on the cell surface, suggesting that proper M11L function requires localization at the infected cell membrane. We propose that M11L is a virulence factor whose function is to recognize an extracellular ligand essential for the cellular inflammatory response.",
author = "Graham, {Kathryn A.} and Andrea Opgenorth and Chris Upton and Douglas McFadden",
year = "1992",
month = "1",
day = "1",
doi = "10.1016/0042-6822(92)90172-L",
language = "English (US)",
volume = "191",
pages = "112--124",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Myxoma virus M11L ORF encodes a protein for which cell surface localization is critical in manifestation of viral virulence

AU - Graham, Kathryn A.

AU - Opgenorth, Andrea

AU - Upton, Chris

AU - McFadden, Douglas

PY - 1992/1/1

Y1 - 1992/1/1

N2 - Myxoma virus (MYX) induces extensive immunosuppression in infected rabbits and is associated with high levels of mortality. The virus encodes multiple gene products designed to circumvent the cellular immune response to the viral infection. Deletion analysis has shown that the M11L open reading frame (ORF) is an important virulence factor which downregulates leukocyte infiltration of MYX-induced tumors. To investigate the role of the M11 L protein in viral pathogenesis, we sequenced the MYX M11L ORF and showed that the sequence has motifs consistent with a 166-aa class III membrane-spanning molecule possessing a single transmembrane helix near the C-terminus and a 142-aa N-terminal extracellular domain that has six cysteine residues plus two consensus N-glycosylation sites. Transcription analysis indicates that M11 L is expressed as an early gene, and surface immunofluorescence studies with anti-M11L antibodies reveal that M11 L protein is transported to the infected cell surface. Immunoprecipitation analysis of an attenuated viral recombinant, vMYX-GF-ΔM11L, indicates that an M11 L variant protein with an altered C-terminus is synthesized at about 45% of wild type levels; however, it is not detectable on the cell surface, suggesting that proper M11L function requires localization at the infected cell membrane. We propose that M11L is a virulence factor whose function is to recognize an extracellular ligand essential for the cellular inflammatory response.

AB - Myxoma virus (MYX) induces extensive immunosuppression in infected rabbits and is associated with high levels of mortality. The virus encodes multiple gene products designed to circumvent the cellular immune response to the viral infection. Deletion analysis has shown that the M11L open reading frame (ORF) is an important virulence factor which downregulates leukocyte infiltration of MYX-induced tumors. To investigate the role of the M11 L protein in viral pathogenesis, we sequenced the MYX M11L ORF and showed that the sequence has motifs consistent with a 166-aa class III membrane-spanning molecule possessing a single transmembrane helix near the C-terminus and a 142-aa N-terminal extracellular domain that has six cysteine residues plus two consensus N-glycosylation sites. Transcription analysis indicates that M11 L is expressed as an early gene, and surface immunofluorescence studies with anti-M11L antibodies reveal that M11 L protein is transported to the infected cell surface. Immunoprecipitation analysis of an attenuated viral recombinant, vMYX-GF-ΔM11L, indicates that an M11 L variant protein with an altered C-terminus is synthesized at about 45% of wild type levels; however, it is not detectable on the cell surface, suggesting that proper M11L function requires localization at the infected cell membrane. We propose that M11L is a virulence factor whose function is to recognize an extracellular ligand essential for the cellular inflammatory response.

UR - http://www.scopus.com/inward/record.url?scp=0026787799&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026787799&partnerID=8YFLogxK

U2 - 10.1016/0042-6822(92)90172-L

DO - 10.1016/0042-6822(92)90172-L

M3 - Article

C2 - 1413498

AN - SCOPUS:0026787799

VL - 191

SP - 112

EP - 124

JO - Virology

JF - Virology

SN - 0042-6822

IS - 1

ER -