The Establishment of Infectious Clone and Single Round Infectious Particles for Coxsackievirus A10

Coxsackievirus A10(CVA10)is one of the major etiological agents of hand,foot,and mouth disease.There are no vaccine and antiviral drugs for controlling CVA10 infection.Reverse genetic tools for CVA10 will benefit its mechanistic study and development of vaccines and antivirals.Here,two infectious clones for the prototype and a Myc-tagged CVA10 were constructed.Viable CVA10 viruses were harvested by transfecting the viral m RNA into human rhabdomyosarcoma(RD)cells.Rescued CVA10 was further confirmed by next generation sequencing and characterized experimentally.We also constructed the vectors for CVA10 subgenomic replicon with luciferase reporter and viral capsid with EGFP reporter,respectively.Co-transfection of the viral replicon RNA and capsid expresser in human embryonic kidney 293 T(HEK293 T)cells led to the production of single round infectious particles(SRIPs).Based on CVA10 replicon RNA,SRIPs with either the enterovirus A71(EVA71)capsid or the CVA10 capsid were generated.Infection by EVA71 SRIPs required SCARB2,while CVA10 SRIPs did not.Finally,we showed great improvement of the replicon activity and SRIPs production by insertion of a cis-active hammerhead ribozyme(HHRib)before the 50-untranslated region(UTR).In summary,reverse genetic tools for prototype strain of CVA10,including both the infectious clone and the SRIPs system,were successfully established.These tools will facilitate the basic and translational study of CVA10.

The transmission mechanism theory of disease dynamics:Its aims,assumptions and limitations

Most of the progress in the development of single scale mathematical and computational models for the study of infectious disease dynamics which now span over a century is build on a body of knowledge that has been developed to address particular single scale descriptions of infectious disease dynamics based on understanding disease transmission process.Although this single scale understanding of infectious disease dynamics is now founded on a body of knowledge with a long history,dating back to over a century now,that knowledge has not yet been formalized into a scientific theory.In this article,we formalize this accumulated body of knowledge into a scientific theory called the transmission mechanism theory of disease dynamics which states that at every scale of organization of an infectious disease system,disease dynamics is determined by transmission as the main dynamic disease process.Therefore,the transmission mechanism theory of disease dynamics can be seen as formalizing knowledge that has been inherent in the study of infectious disease dynamics using single scale mathematical and computational models for over a century now.The objective of this article is to summarize this existing knowledge about single scale modelling of infectious dynamics by means of a scientific theory called the transmission mechanism theory of disease dynamics and highlight its aims,assumptions and limitations.