tailieunhanh - Báo cáo y học: "Attenuation of vaccinia virus by the expression of human Flt3 ligand"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Attenuation of vaccinia virus by the expression of human Flt3 ligand | Zurkova et al. Virologyjournal 2010 7 109 http content 7 1 109 VIROLOGY JOURNAL RESEARCH Open Access Attenuation of vaccinia virus by the expression of human Flt3 ligand Kamila Zurkova 1 Petr Hainz1 Jitka Krystofova1 Luda Kutinova1 Miloslav Sanda2 and Sarka Nemeckova1 Abstract Background Vaccinia virus one of the best known members of poxvirus family has a wide host range both in vivo and in vitro. The expression of Flt3 ligand FL by recombinant vaccinia virus rVACV highly influenced properties of the virus in dependence on the level of expression. Results High production of FL driven by the strong synthetic promoter decreased the growth of rVACV in macrophage cell line in vitro as well as its multiplication in vivo when inoculated in mice. The inhibition of replication in vivo was mirrored in low levels of antibodies against vaccinia virus anti-VACV which nearly approached to the negative serum level in non-infected mice. Strong FL expression changed not only the host range of the recombinant but also the basic protein contents of virions. The major proteins - H3L and D8L - which are responsible for the virus binding to the cells and 28 K protein that serves as a virulence factor were changed in the membrane portion of P13-E L-FL viral particles. The core virion fraction contained multiple larger uncleaved proteins and a higher amount of cellular proteins compared to the control virus. The overexpression of FL also resulted in its incorporation into the viral core of P13-E L-FL IMV particles. In contrary to the equimolar ratio of glycosylated and nonglycosylated FL forms found in cells transfected with the expression plasmid the recombinant virus incorporated mainly the smaller nonglycosylated FL. Conclusions It has been shown that the overexpression of the Flt3L gene in VACV results in the attenuation of the virus in vivo. Background Vaccinia virus VACV is the best-studied member of the Orthopoxvirus genus of the poxvirus family. It has