Apoptin enhances the oncolytic activity of vaccinia virus
Kochneva, G.V.; Babkina, I.N.; Lupan, T.A.; Grazhdantseva, A.A.; Iudin, P.V.; Sivolobova, G.F.; Shvalov, A.N.; Popov, E.G.; Babkin, I.V.; Netesov, S.V.; Chumakov, P.M.
Molekuliarnaia Biologiia 47(5): 842-852
2013
ISSN/ISBN: 0026-8984 PMID: 25509357 Document Number: 666276
Chicken anemia virus gene encoding apoptin, a selective killer of cancer cells was synthesized and inserted into vaccinia virus (strain L-IVP) genome. The insertion has replaced major part of the viral C11R gene encoding viral growth factor (VGF), which is important for the virulence. The recombinant virus VVdGF-ApoS24/2 was obtained through the transient dominant selection technique with the use of puromycin resistance gene as the selective marker. The expression apoptin gene from a synthetic early-late promoter of vaccinia virus effectively provides accumulation of the protein in the cells infected with the VVdGF-ApoS24/2 virus. Despite the presence of virus growth factor signal peptide at apoptin N-terminal secretion of the recombinant protein into culture medium did not occur. The recombinant virus VVdGF-ApoS24/2 was found to have a significantly greater selective lyticactivity on human cancer cell lines (A549, A431, U87MG, RD and MCF7) as compared with the parent strain L-IVP and its variant VVdGF2/6 with the deletion of the C11R gene. The results suggest that the use of apoptin represents a promising approach for improving the natural anticancer activities of vaccinia virus.