Very different kinds of pathogen-in this case, one a virus, the other a mycoplasma- can act as if cooperating when infecting cultured cells, with one augmenting the potency of the other, according to Peter Lidsky and Vadim I. Agol of the Russian Academy of Medical Sciences, Moscow, Russia, and their collaborators at the Academy and the nearby M. V. Lomonosov Moscow State University, as well as at Radboud University Nijmegen Medical Centre in Nijmegen, the Netherlands.
Thus a DNAase from a simultaneously infecting mycoplasma enhances the cell-killing activity of the encephalomyocarditis (EMC) virus, they report in the October Journal of Virology (83:9940-9951).
The Russian and Dutch microbiologists were analyzing what happens when EMC virus infects cultured cells. They were following up earlier studies in which Agol and his collaborators learned that poliovirus sometimes activates- but at other times suppresses- apoptosis (cell killing) in cells that it infects. Their 1995 report not only describes this apoptosis-triggering activity, but also presents the first case of apoptosis suppression via an RNA virus with a simple genome, he says. Both poliovirus andEMCare picornaviruses. While poliovirus infects the gastrointestinal tract, EMC infects the heart, making it a cardiovirus and thus a member of a more recently recognized group of human pathogens, according to Agol.
What the Russian-Dutch team studying EMC did not realize at first is that some of their cell cultures were contaminated with Mycoplasma hyorhinis. Thus, sometimes EMC degraded host-cell DNA, in a manner similar to what happens during apoptosis. However, compounds that ordinarily suppress apoptosis failed to do so. The reason is that a DNAase from the mycoplasma was responsible for degrading the cellular DNA and, thereby, enhancing the potency of the viral infection. Lidsky, Agol, and their collaborators call this phenomenon involving such different pathogens "cooperation."
Cardioviruses in mycoplasma-free cultures also trigger apoptosis, according to Agol. However, he says, the viral leader protein can suppress it, preventing DNA degradation in these cells.
"We initially observed that cardioviruses triggered in infected cells a very strong DNA degradation, which is a hallmark of apoptosis," Agol says. "One day, Peter Lidsky came to me and said he had obtained evidence that this DNAase likely originated from mycoplasma, a frequent, undesirable contaminant of cell cultures. He and [another colleague] Lyudmila Romanova were extremely disappointed, thinking that their results should be thrown away." However, they came to view the findings differently- as reflecting what likely occurs often in nature, simultaneous infection with viral and microbial agents.
Uncovering evidence for cooperation between such different pathogens is a "pioneering piece of work," says Andrei V. Gudkov of Roswell Park Cancer Institute in Buffalo, N.Y., referring to the research of the Dutch and Russian microbiologists. "Their data are consistent with the hypothesis that the EMC virus infection ‘opens up' the mammalian cell to DNAase of mycoplasma origin, thereby changing the cytotoxicity pattern of an otherwise quite benign mycoplasma infection." He also wonders whether and how mycoplasma infections affect the titer of viral progeny. On the other hand, he adds, these findings may simply "represent a completely artificial clash between two parasites which provides no benefit for either."
"However," Gudkov continues, "the more interesting hypothesis is that this outcome of viral infection reflects an adaptive survival mechanism of mycoplasma. In fact, mycoplasma seems to induce an apoptosislike outcome of viral infection, something that practically all viruses try to avoid." The findings support the importance of maintaining healthy microflora, and the need for more conservative use of antimicrobials, he says. "I would not be surprised that one day we will have to conclude that subjects with chronic mycoplasma infections are more resistant to certain viruses."
David Holzman
David Holzman is the Microbe Journal Highlights Editor.
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