The Role Of Honokiol In Anti-hepesvirus Infection And The Role Of STAT3 In MHV68 Infection

Herpesviridae is one of important pathogens which can establish the latency in host.Recently,herpesvirus infection has a worldwide seroprevalence of 20~95% in world population,with the higher frequencies being in the developing world.For example,HSV is carried over two third of the population in world,this rate was over 90% in HCMV infection and over 50% in EBV or KSHV infection.Herpesvirus infection would result in different clinical disease such as oral blisters,kerato-conjunctivitis,meningoencephalitis,lymphomas and Kaposi's sarcoma(KS);even more serious disastrous effect like blindness and death.Nowadays there is no effective vaccine for large proportion of herpesvirus like HSV and KSHV,except varicella-zoster virus.The anti-herpesvirus agents approved in clinical application are all inhibit viral DNA polymerase and could not avoid the resistant strains and have relatively high side effects.Therefore,it's necessary to seek novel anti-herpesvirus agents.In this paper we perform two projects including: honokiol plays a role in antiherpesvirus and how STAT3 activation affects MHV68 de novo infection.Honokiol,which is pleiotropic natural active compound isolated from traditional Chinese herbal medicine Magnolia,plays a role in anti-tumor,anti-inflammation,antithrombotic and anti-microbial.However,the researches about its anti-virus is limited.In this paper,we construct an infection model by the recombinant virus strains like HSV-1-GFP?KSHV-RGB-BAC16?MHV68-H2b-YFP whose genome fuses the gene coding the fluorescent protein.The results from fluorescence microscope observation,western blotting and real time-quantitative polymerase chain reaction,firstly reveal that honokiol can inhibit human herpesvirus,not only alpha-herpesvirus but also gammaherpesvirus,even murine herpesvirus 68.Preliminary results suggest its antiherpesvirus mechanisms involve in inhibiting DNA replication,reducing gene expression and viral particle production,and it has no effect on the virus entry.It is meaningful for the anti-herpesvirus treatment because of a close relationship between virus infection and host factors like STAT3.STAT3 has double functions contain signal transduction and as a transcriptional factor,and it plays a complicated role in virus infection.In fact,many active compounds achieve their bio-functions by inhibiting the target of STAT3 signal pathway.It's doubt whether honokiol influences the herpesvirus de novo infection by this way.First of all,we had better understand the relationship between STAT3 activation and MHV68 de novo infection because of MHV68 usually as a model to research the human herpesvirus.Herein,we found the inhibition of JAK-STAT3 signal pathway results in reducing MHV68 infection.The MEF cell lines over-expressing STAT3 and STAT3 C proteins were constructed to illuminate the relationship conveniently.The results suggest overexpression of STAT3 and STAT3 C protein in MEF cell lines would increase the MHV68 infection and promotes its reactivation.These innovative study provide a drug candidate to anti-herpesvirus,preliminary results show STAT3 activation increases MHV 68 de novo infection and promotes MHV68 reactivation.And that lays a basis for understanding the molecular mechanism about the STAT3 and MHV68 infection,paves the way for further research of its antivirus mechanism.