Oncolytic viruses, including live attenuated measles virus (MV) vaccine strains, have recently been shown as promising therapeutic agents against human malignancies. In this study, the oncolytic potential of the attenuated vaccine strain Leningrad-16 (L-16) of MV was evaluated in a panel of human metastatic melanoma cell lines. The L-16 measles virus was shown to replicate within melanoma cells mediating direct cell killing of tumor cells, although all melanoma cell lines varied in regard to their ability to respond to L-16 MV infection, as revealed by the different pattern of the Interferon Stimulated Gene expression, cytokine release and mechanisms of cell death. Furthermore, the statistically significant L-16 measles virus related tumor growth inhibition was demonstrated in a melanoma xenograft model. Therefore, L-16 MV represents an appealing oncolytic platform for target delivery of therapeutic genes along with other attenuated measles virus strains.

Aim. Some viruses can subvert host defense mechanism, autophagy, to their own benefit. We analysed the effect of Rubella virus (RV) infection on autophagy in human alveolar epithelial cells A549. Materials and methods. Cells were infected with the wild type and lab-attenuated strain, C-77w and C-77a, respectively, with a multiplicity of infection of 1.0, in parallel, the expression level of genes encoding Beclin1, Atg5, Rab7, and p62 (SQSTM1) proteins participating in different steps of autolysosome formation was measured. To investigate the role of autophagy on RV replication cycle, we measured the amount of infectious RV particles, together with the viral RNA in supernatants and cell lysates, after incubation of A549 cells with wild type or attenuated strain in the presence of the autophagy inhibitor, Bafilomycin A1, or inducer, Rapamycin. Results. The significant increase in Beclin1 and Atg5 gene expression at 24-48 (for the wild type) and 24-72 (for the attenuated type) hours after infection was observed, while significant induction of either Rab7 or SQSTM1 gene expression was not noticed. This effect was correlated with more delayed increase of IFNβ expression and IFNβ-mediated pro-apoptotic gene expression leading to apoptotic cell death 72-96 hours after infection. Moreover, Bafilomycin A1 diminished the RV infection non significantly, as evidenced by the RT-qPCR and plaque assay, while Rapamycin increased the amount of infectious RV particles released by the infected cells more dramatically with wild type comparing with attenuated strain. Conclusion. Thus, we hypothesized that RV can use an antiviral mechanism to prevent degradation and ensure its replication, differentially regulating the process of autophagy, by stimulating the initiation and suppression of later steps.

Шешнёв Александр Сергеевич, кандидат географических наук, ведущий инженер лаборатории геоэкологии, Саратовский национальный исследовательский государственный университет имени Н. Г. Чернышевского,

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