An interaction domain in human SAMD9 is essential for myxoma virus host-range determinant M062 antagonism of host anti-viral function.
In humans, deleterious mutations in the sterile α motif domain protein 9 (SAMD9) gene are associated with cancer, inflammation, weakening of the immune response, and developmental arrest. However, the biological function of SAMD9 and its sequence-structure relationships remain to be characterized. Previously, we found that an essential host range factor, M062 protein from myxoma virus (MYXV), antagonized the function of human SAMD9. In this study, we examine the interaction between M062 and human SAMD9 to identify regions that are critical to SAMD9 function. We also characterize the in vitro kinetics of the interaction. In an infection assay, exogenous expression of SAMD9 N-terminus leads to a potent inhibition of wild-type MYXV infection. We reason that this effect is due to the sequestration of viral M062 by the exogenously expressed N-terminal SAMD9 region. Our studies reveal the first molecular insight into viral M062-dependent mechanisms that suppress human SAMD9-associated antiviral function.
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Bernice
B
Nounamo
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Yibo
Y
Li
School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
Peter
P
O'Byrne
School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
Aoife M
AM
Kearney
School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland. Electronic address: amirrafk@tcd.ie.
Amir
A
Khan
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR, USA; The Center for Microbial Pathogenesis and Host Inflammatory Responses, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Electronic address: jliu4@uams.edu.
Jia
J
Liu
D000072283:A549 Cells; D000818:Animals; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006367:HeLa Cells; D058507:Host Specificity; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009233:Myxoma virus / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; C000619471:M062 protein, myxoma virus; D011506:Proteins; C514443:SAMD9 protein, human; D014764:Viral Proteins
C7L superfamily; Host range factor; Immunoprecipitation; MYXV; Polymerization; Protein-protein interaction; SAMD9; Surface plasmon resonance (SPR)