TY - JOUR

T1 - Bioselection of coxsackievirus B6 strain variants with altered tropism to human cancer cell lines

AU - Svyatchenko, Victor A.

AU - Ternovoy, Vladimir A.

AU - Kiselev, Nikolai N.

AU - Demina, Anna V.

AU - Loktev, Valery B.

AU - Netesov, Sergey V.

AU - Chumakov, Peter M.

N1 - Funding Information: Funding The study was supported by the Grant number 14-50-00060 from the Russian Science Foundation. Publisher Copyright: © 2017, Springer-Verlag GmbH Austria.

PY - 2017/11/1

Y1 - 2017/11/1

N2 - Cancer cells develop increased sensitivity to members of many virus families and, in particular, can be efficiently infected and lysed by many low-pathogenic human enteroviruses. However, because of their great genetic heterogeneity, cancer cells display different levels of sensitivity to particular enterovirus strains, which may substantially limit the chances of a positive clinical response. We show that a non-pathogenic strain of coxsackievirus B6 (LEV15) can efficiently replicate to high titers in the malignant human cell lines C33A, DU145, AsPC-1 and SK-Mel28, although it displays much lower replication efficiency in A431 and A549 cells and very limited replication ability in RD and MCF7 cells, as well as in the normal lung fibroblast cell line MRC-5 and the immortalized mammary epithelial cell line MCF10A. By serial passaging in RD, MCF7 and A431 cells, we obtained LEV15 strain variants that had acquired high replication capacity in the appropriate carcinoma cell lines without losing their high replication capability in the original set of cancer cell lines and had limited replication capability in untransformed cells. The strains demonstrated improved oncolytic properties in nude-mouse xenografts. We identified nucleotide changes responsible for the phenotypes and suggest a bioselection approach for a generation of oncolytic virus strains with a wider spectrum of affected tumors.

AB - Cancer cells develop increased sensitivity to members of many virus families and, in particular, can be efficiently infected and lysed by many low-pathogenic human enteroviruses. However, because of their great genetic heterogeneity, cancer cells display different levels of sensitivity to particular enterovirus strains, which may substantially limit the chances of a positive clinical response. We show that a non-pathogenic strain of coxsackievirus B6 (LEV15) can efficiently replicate to high titers in the malignant human cell lines C33A, DU145, AsPC-1 and SK-Mel28, although it displays much lower replication efficiency in A431 and A549 cells and very limited replication ability in RD and MCF7 cells, as well as in the normal lung fibroblast cell line MRC-5 and the immortalized mammary epithelial cell line MCF10A. By serial passaging in RD, MCF7 and A431 cells, we obtained LEV15 strain variants that had acquired high replication capacity in the appropriate carcinoma cell lines without losing their high replication capability in the original set of cancer cell lines and had limited replication capability in untransformed cells. The strains demonstrated improved oncolytic properties in nude-mouse xenografts. We identified nucleotide changes responsible for the phenotypes and suggest a bioselection approach for a generation of oncolytic virus strains with a wider spectrum of affected tumors.

UR - http://www.scopus.com/inward/record.url?scp=85026551082&partnerID=8YFLogxK

U2 - 10.1007/s00705-017-3492-0

DO - 10.1007/s00705-017-3492-0

M3 - Article

C2 - 28766058

AN - SCOPUS:85026551082

VL - 162

SP - 3355

EP - 3362

JO - Archives of Virology

JF - Archives of Virology

SN - 0304-8608

IS - 11

ER -