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Virology. 2017 Mar;503:94-102. doi: 10.1016/j.virol.2017.01.004. Epub 2017 Jan 31.

An interaction domain in human SAMD9 is essential for myxoma virus host-range determinant M062 antagonism of host anti-viral function.

Author information

1
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
2
School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
3
School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland. Electronic address: amirrafk@tcd.ie.
4
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.

Abstract

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.

KEYWORDS:

C7L superfamily; Host range factor; Immunoprecipitation; MYXV; Polymerization; Protein-protein interaction; SAMD9; Surface plasmon resonance (SPR)

PMID:
28157624
PMCID:
PMC5419587
DOI:
10.1016/j.virol.2017.01.004
[Indexed for MEDLINE]
Free PMC Article

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