The Studys Of A New Method To Prevent And Cure Infection Of Coxsaekievirus

Coxsackievirus B3 (CVB3), a member of the Enterovirus genus of the family Picornaviridae, is associated with a number of diverse syndromes including meningitis, febrile illness, diabetes, and is commonly associated with virus-induced heart disease in adults and children, and especially highly susceptible for infants and newborns. Despite its significant impact on human health, there are no therapeutic interventions to treat CVB3 infections.Here, we explored a new ’Trojan horse’ strategy to kill CVB3-infected cells, which prevents the ulterior infction inducing exacerbation such as in viral heart diseases. By exploiting 3C protease, which is highly conserved in family Picornaviridae and plays an indispensable role in virus replicative cycle, cleaving and facilitating the artificial Caspase-3 would be used clinically in the treatment is the macro design. As natural Caspase-mediated apoptosis is crucial machinery for cell survival in the struggle between virus and host, we engineered a transducing, modified, apoptosis-promoting caspase-3 protein, which substitutes CVB3 proteolytic cleavage sites for endogenous ones and efficiently transduces about 100% of cells, but remains inactive in uninfected cells. In CVB3-infected cells, artificial Caspase-3 becomes processed into an active form by 3C protease, resulting in apoptosis of the infected cell, and then stops the paroxysm. This strategy could also be applied to other pathogens encoding specific proteases, such as hepatitis C virus, cytomegalovirus and malaria.According to previous study results in our team, this continued work first constructed plasmid pcDNATM3.1(+)-recombination-signal peptide-caspase-3-6Aa (hereafter referred to as p-rc-sig-6), virus vectors contained modified Caspase-3, adenvirus vectors Ad-recombination-Caspase-3-6Aa (hereafter referred to as Ad-rc-6) and Ad-recombination-Caspase-3-8Aa (hereafter referred to as Ad-rc-8), and lentiviral vector LV-recombination-signal peptide-Caspase-3-6Aa (hereafter referred to as LV-rc-sig-6). And then, we validate the infected cells apoptosis efficiency in mammalian cells, the treatment group showed higher cell ability than control group, signifficiently. Subsequently, the evaluation survival rate of infected mice treated with or without the virus vectors showed that the treat stratege could prevent CVB3-induced death. Those results suggested the new stratege we proposed is valid to handle the CVB3 infection.