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Title: Global foot-and-mouth disease research update and gap analysis: 7 - pathogenesis and molecular biology

item ROBINSON, L. - Insight Editing London
item KNIGHT-JONES, T.J.D. - International Livestock Research Institute (ILRI) - Zambia
item CHARLESTON, B. - The Pirbright Institute
item Rodriguez, Luis
item Gay, Cyril
item SUMPTION, K.J. - Food And Agriculture Organization Of The United Nations-European Commission For The Control Of Foot
item VOSLOO, W. - Australian Animal Health

Submitted to: Transboundary and Emerging Diseases
Publication Type: Review Article
Publication Acceptance Date: 4/21/2016
Publication Date: 4/21/2016
Citation: Robinson, L., Knight-Jones, T., Charleston, B., Rodriguez, L.L., Gay, C.G., Sumption, K., Vosloo, W. 2016. Global foot-and-mouth disease research update and gap analysis: 7 - pathogenesis and molecular biology. Transboundary and Emerging Diseases. 63:63-71. doi: 10.1111.tbed.12520.

Interpretive Summary: We assessed research knowledge gaps in the fields of FMDV (foot-and-mouth disease virus) pathogenesis and molecular biology by performing a literature review (2011–15) and collecting research updates (2014) from 33 institutes from across the world. Findings were used to identify priority areas for future research. There have been important advances in FMDV pathogenesis; FMDV remains in lymph nodes of many recovered animals that otherwise do not appear persistently infected, even in species previously not associated with the carrier state. Whether virus retention helps maintain host immunity and/or virus survival is not known. Studies of FMDV pathogenesis in wildlife have provided insights into disease epidemiology, in endemic and epidemic settings. Many aspects of FMDV infection and virus entry remain unknown; however, at the cellular level, we know that expression level and availability of integrins (that permit viral entry), rate of clearance of infected cells and strength of anti-viral type I IFN (interferon) response are key determinants of tissue tropism. Extending findings to improved understanding of transmission requires a standardized approach and adoption of natural routes of infection during experimental study. There has been recognition of the importance of autophagosomes for FMDV entry into the cytoplasm following cell surface receptor binding, and that distinct internal cellular membranes are exploited for viral replication and immune evasion. New roles for viral proteins in blocking type I IFN production and downstream signalling have been identi'ed facilitating research in anti-viral therapeutics. We know more about how infection affects cell protein expression, and research into molecular determinants of capsid stability has aided the development of stable vaccines. We have an expanding knowledge of viral and host molecular determinates of vir-ulence and infectiousness, and of how phylogenetics may be used to estimate vaccine match and strain distribution. With ongoing advances, these areas could translate into significantly improved disease control.

Technical Abstract: In 2014, the GFRA (Global Foot-and-mouth disease Research Alliance) conducted a gap analysis of FMD (Foot-and-Mouth Disease) research. This work has been updated and reported in a series of papers, in this article we report findings in the fields of 1) pathogenesis and 2) molecular biology. The article consists of the following four sections for each field: 1) Research priorities identifed in the 2010 GFRA gap analysis (only reported for Pathogenesis). 2) Results from a literature review of FMD research published between 1st June 2011 and 31st October 2015. 3) Ongoing research reported by institutions, assessed June 2014. 4) Research priorities updated in the light of the above findings. An overview of the study and background information, including review methods, are presented in the first paper in the series.