Antiapoptotic activity of the cardiovirus leader protein, a viral "security" protein

Romanova, L.I.; Lidsky, P.V.; Kolesnikova, M.S.; Fominykh, K.V.; Gmyl, A.P.; Sheval, E.V.; Hato, S.V.; van Kuppeveld Frank, J.M.; Agol, V.I.

Авторы: Romanova Lyudmila I., Lidsky Peter V., Kolesnikova Marina S., Fominykh Ksenia V., Gmyl Anatoly P., Sheval Eugene V., Hato Stanleyson V., van Kuppeveld Frank J.M., Agol Vadim I.
Журнал: Journal of Virology
Том: 83
Номер: 14
Год издания: 2009
Издательство: American Society for Microbiology
Местоположение издательства: United States
Первая страница: 7273
Последняя страница: 7284
DOI: 10.1128/JVI.00467-09
Аннотация: Apoptosis is a common antiviral defensive mechanism that potentially limits viral reproduction and spread. Many viruses possess apoptosis-suppressing tools. Here, we show that the productive infection of HeLa cells with encephalomyocarditis virus (a cardiovirus) was not accompanied by full-fledged apoptosis (although the activation of caspases was detected late in infection) but rather elicited a strong antiapoptotic state, as evidenced by the resistance of infected cells to viral and nonviral apoptosis inducers. The development of the antiapoptotic state appeared to depend on a function(s) of the viral leader (L) protein, since its mutational inactivation resulted in the efflux of cytochrome c from mitochondria, the early activation of caspases, and the appearance of morphological and biochemical signs of apoptosis in a significant proportion of infected cells. Infection with both wild-type and L-deficient viruses induced the fragmentation of mitochondria, which in the former case was not accompanied with cytochrome c efflux. Although the exact nature of the antiapoptotic function(s) of cardioviruses remains obscure, our results suggested that it includes previously undescribed mechanisms operating upstream and possibly downstream of the mitochondrial level, and that L is involved in the control of these mechanisms. We propose that cardiovirus L belongs to a class of viral proteins, dubbed here security proteins, whose roles consist solely, or largely, in counteracting host antidefenses. Unrelated L proteins of other picornaviruses as well as their highly variable 2A proteins also may be security proteins. These proteins appear to be independent acquisitions in the evolution of picornaviruses, implying multiple cases of functional (though not structural) convergence.
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Antiapoptotic activity of the cardiovirus leader protein, a viral "security" proteinстатья