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Research Project: Intervention Strategies to Support the Global Control and Eradication of Foot-and-Mouth Disease Virus (FMDV)

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Title: Insights into jumonji c-domain containing protein 6 (JMJD6): a multifactorial role in FMDV replication in cells

item Lawrence, Paul
item Rieder, Aida - Elizabeth

Submitted to: Virus Genes
Publication Type: Review Article
Publication Acceptance Date: 3/17/2017
Publication Date: 3/31/2017
Citation: Lawrence, P.J., Rieder, A.E. 2017. Insights into jumonji c-domain containing protein 6 (JMJD6): a multifactorial role in FMDV replication in cells. Virus Genes. 53(3):340-351.

Interpretive Summary: This review article summarizes everything that is currently known about a protein called JMJD6 that was shown to be important for the replication of foot-and-mouth disease virus (FMDV). JMJD6 was recently shown to function as an alternative receptor for laboratory adapted FMDV to attach to cells for infection. This summary of JMJD6 shows other potential roles that it might play in virus infection. JMJD6 also may be a target for future bio-therapeutic interventions against FMDV.

Technical Abstract: The Jumonji C-domain containing protein 6 (JMJD6) has had a convoluted history. It was first identified as the phosphatidylserine receptor (PSR) on the cell surface responsible for recognizing phosphatidylserine on the surface of apoptotic cells resulting in their engulfment by phagocytic cells. Subsequent study revealed a nuclear sub-cellular localization, where JMJD6 participated in lysine hydroxylation and arginine demethylation of histone proteins and other non-histone proteins. Interestingly, to date, JMJD6 remains the only known arginine demethylase with a growing list of known substrate molecules. These conflicting associations rendered the sub-cellular localization of JMJD6 to be quite nebulous. Further muddying this area, two different groups illustrated that JMJD6 could be induced to redistribute from the cell surface to the nucleus of a cell. More recently, JMJD6 was demonstrated to be a host factor contributing to the foot-and-mouth disease virus (FMDV) life cycle, where it was exploited for arginine demethylase activity, but also served as an alternative virus receptor. This review attempts to coalesce these divergent roles for a single protein into one cohesive account. Given the diverse functionalities already characterized for JMJD6, it is likely to continue to be a confounding protein resulting in much contention going into the near future.