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Journal of Virology, October 2009, p. 9940-9951, Vol. 83, No. 19
0022-538X/09/$08.00+0     doi:10.1128/JVI.01167-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Interactions between Viral and Prokaryotic Pathogens in a Mixed Infection with Cardiovirus and Mycoplasma{triangledown}

Peter V. Lidsky,1,{dagger} Lyudmila I. Romanova,1,{dagger} Marina S. Kolesnikova,1 Maryana V. Bardina,1 Elena V. Khitrina,1 Stanleyson V. Hato,3 Frank J. M. van Kuppeveld,3 and Vadim I. Agol1,2*

M. P. Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, Moscow Region 142782, Russia,1 M. V. Lomonosov Moscow State University, Moscow 119899, Russia,2 Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, Nijmegen 6500 HB, The Netherlands3

Received 8 June 2009/ Accepted 6 July 2009

In the natural environment, animal and plant viruses often share ecological niches with microorganisms, but the interactions between these pathogens, although potentially having important implications, are poorly investigated. The present report demonstrates, in a model system, profound mutual effects of mycoplasma and cardioviruses in animal cell cultures. In contrast to mycoplasma-free cells, cultures contaminated with Mycoplasma hyorhinis responded to infection with encephalomyocarditis virus (EMCV), a picornavirus, but not with poliovirus (also a picornavirus), with a strong activation of a DNase(s), as evidenced by the TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) immunofluorescence assay and electrophoretic analysis of host DNA. This degradation was reminiscent of that observed upon apoptosis but was caspase independent, judging by the failure of the specific pan-caspase inhibitor Q-VD-OPh to prevent it. The electrophoretic mobility of the enzyme responsible for DNA degradation and dependence of its activity on ionic conditions strongly suggested that it was represented by a DNase(s) of mycoplasma origin. In cells not infected with EMCV, the relevant DNase was dormant. The possibility is discussed that activation of the mycoplasma DNase might be linked to a relatively early increase in permeability of plasma membrane of the infected cells caused by EMCV. This type of unanticipated virus-mycoplasma "cooperation" may exemplify the complexity of pathogen-host interactions under conditions when viruses and microorganisms are infecting the same host. In the course of the present study, it was also demonstrated that pan-caspase inhibitor zVAD(OMe).fmk strongly suppressed cardiovirus polyprotein processing, illustrating an additional pitfall in investigations of viral effects on the apoptotic system of host cells.


* Corresponding author. Mailing address: Institute of Poliomyelitis, Moscow Region 142782, Russia. Phone: 7 (495) 439 9026. Fax: 7 (495) 439 9321. E-mail: agol{at}belozersky.msu.ru

{triangledown} Published ahead of print on 15 July 2009.

{dagger} P.V.L. and L.I.R. contributed equally to this study.


Journal of Virology, October 2009, p. 9940-9951, Vol. 83, No. 19
0022-538X/09/$08.00+0     doi:10.1128/JVI.01167-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.