Inhibition of macrophage activation by the myxoma virus M141 protein (vCD200).
The M141 protein of myxoma virus (MYXV) is a viral CD200 homolog (also called vOX-2) that inhibits macrophage activation in infected rabbits. Here, we show that murine myeloid RAW 264.7 cells became activated when infected with MYXV in which the M141 gene was deleted (vMyx-M141KO) but not with the parental wild-type MYXV. Moreover, transcript and protein levels of tumor necrosis factor and granulocyte colony-stimulating factor were rapidly upregulated in an NF-kappaB-dependent fashion in the RAW 264.7 cells infected with vMyx-M141KO. M141 protein is present in the virion and counteracts this NF-kappaB activation pathway upon infection with the wild-type MYXV. Our data suggest that upregulation of these classic macrophage-related proinflammatory cytokine markers following infection of myeloid cells with the M141-knockout MYXV is mediated via the rapid activation of the cellular NF-kappaB pathway.
Zhang
Leiliang
L
Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, 32610, USA.
Stanford
Marianne
M
Liu
Jia
J
Barrett
Catherine
C
Jiang
Lei
L
Barclay
A Neil
AN
McFadden
Grant
G
D000818:Animals; D015703:Antigens, CD; D002460:Cell Line; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000821:virology*; D051379:Mice; D022423:Myeloid Cells / Q000821:virology; D009233:Myxoma virus / Q000276:immunology* / Q000472:pathogenicity; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D015854:Up-Regulation; D014764:Viral Proteins / Q000502:physiology*
D015703:Antigens, CD; C501251:M141R protein, myxoma virus; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D016179:Granulocyte Colony-Stimulating Factor; C042739:antigens, CD200