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

Abstract

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.

Dose‐dependent effects of the caspase inhibitor Q‐VD‐OPh on different apoptosis‐related processes

“…However, although the recommended working concentration for the use in cell cultures is usually 10–20 µM, the inhibitors are often added at higher doses (10 out of 19 randomly chosen papers reported the use of Q‐VD‐OPh at 40–100 µM concentration). The limited specificity has already been warranted for other caspase inhibitors than Q‐VD‐OPh [Ekert et al, 1999; Martin et al, 2007; Lidsky et al, 2009]. The latter is supposed to be more selective for the caspase family as it does not cross‐react with cathepsins (except for cathepsin H), granzyme B, and calpains [Chauvier et al, 2007] but the hypothesis that even this inhibitor may have non‐caspase targets cannot be ruled out.…”

Facilitative and antagonistic interactions between plant viruses in mixed infections

“…Most attention in virology research has traditionally been given to properties of individual virus species, whereas comparatively little attention has been paid to within‐host interactions between viruses or between viruses and microorganisms in multiple infections (Lidsky et al ., 2009; Rentería‐Canett et al ., 2011). Meanwhile, accumulating evidence for ubiquitous viral infections in the plant and animal (including humans) kingdoms strongly suggests that mixed viral infections may be the rule rather than the exception in nature (DaPalma et al ., 2010; Waner, 1994), which seems to be typical of the infections induced by parasites (Balmer et al ., 2009).…”

Role of Sexually-Transmitted Infections in the Structural and Functional Reorganization of the Prostate

“…M. genitalium can induce infl ammatory reaction in infected tissues by stimulation of NF-kB transcription factor in epithelial cells through TLR2/6 [10]. Interactions of mycoplasmas with various associations of viruses and other infectious agents with induction of cell apoptosis or necrosis are also probable [8].…”