Saturday, February 19, 2011

Virus, Parasite May Combine to Increase Harm to Humans

A parasite and a virus may be teaming up in a way that increases the parasite's ability to harm humans, scientists at the University of Lausanne in Switzerland and Washington University School of Medicine in St. Louis recently reported in Science.

"This is the first reported case of a viral infecti
on in a pathogen of this type leading to increased rather than reduced pathogenicity," says Stephen Beverley, PhD, the Marvin M. Brennecke Professor and head of the Department of Molecular Microbiology at Washington University School of Medicine. "It raises a number of important questions, including whether we can use antiviral strategies to reduce the damage caused by forms ofLeishmania that carry viruses."When the parasite Leishmaniainfects a human, immune system cells known as macrophages respond. However, some Leishmaniastrains are infected with a virus that can trigger a severe response in macrophages, allowing the parasite to do more harm in animal infections. In humans, the parasite's viral infection may be why some strains of Leishmania in Central and South America tend to cause a disfiguring form of disease that erodes the soft tissues around the nose and mouth.
In tests in mice and hamsters using parasite strains taken from the wild, Fasel and Saravia showed that only someViannia strains spread rapidly and cause high levels of inflammation and damage similar to that seen in mucocutaneous leishmaniasis.
A breakthrough came when researchers realized that the rapid, highly damaging form of infection relied on an immune system sensor protein called TLR3. This protein is found in intracellular vesicles, which are compartments inside macrophages also known to host the parasite.
"Those vesicles are where the rendezvous between host, parasite and virus takes place," Fasel says. "TLR3 normally helps the immune system fight infections, but when we deleted it in mice and repeated the experiment, infections with virus-infected Leishmania were less harmful."
Researchers sorted the Leishmania into viral-infected and non-infected strains and found that the more serious infections in laboratory animals were much more likely to be caused by viral-infected Leishmania.
Beverley's group has been exploring the role of viral infections of Leishmania in the evolution of the RNA interference pathway, which can help fight viruses.
"Surprisingly many Leishmania species have lost the RNAi interference pathway, and one force contributing to this loss could be the successful infection of the parasite by viruses," he says. "This hints at the possibility of an evolutionary trade-off, suggesting that the loss of RNAi could be balanced if the parasite gained some type of advantage when infected by a virus."
To ensure that genetic differences in the wild strains weren't interfering with the results, Lon-Fye Lye, PhD, staff scientist, and Suzanne Hickerson, senior research technician, both of Beverley's lab, supplied lines of genetically identical Leishmania with and without the virus. As in the prior comparisons, virally-infected Leishmania caused more disease and provoked a stronger response from macrophages.
According to Beverley, the results suggest that some viral infections in Leishmania may be improving the parasite's chances to infect the mammalian host's immune cells. He speculates that this increased pathogenicity may be one evolutionary trade-off that makes losing the RNAi pathway worthwhile for Leishmania and other microbes.
This finding is interesting to me because I was under the impression (or the dogma) that viral infection can never be mutualistic, it will be commensalistic to the host at best. It obviously raises the question, then, too, that if a virus can be beneficial for a parasite, can one be beneficial for a human? (Bob has touched on this in class, but nothing has yet been proved). 

-Catalina Angel

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