image: Toll-like receptor 2 is normally localized to the cell membrane (green outlines, left panel). However, a KSHV protein affects the normal distribution (diffuse green, right panel). Endoplasmic reticulum is shown in red. view more
Credit: HZI
This news release is available in German.
The Kaposi's sarcoma-associated herpesvirus (KSHV), a gammaherpesvirus that can cause multiple forms of cancer, establishes lifelong infections within the body. To do so the virus has to find a way to modulate the immune system of its host.
„Intruders are usually fought off immediately by an antiviral immune response that is triggered by sensors including the toll-like receptors (TLR)," says HZI researcher Dr. Kendra Bussey, author of the study that was published in the "Journal of Virology". Toll-like receptors detect the virus by binding to structures on the viral surface or the viral DNA, and trigger a signal chain that in the end leads to an antiviral immune response. Ideally this means that the pathogen is eliminated immediately. This mechanism, however, does not seem to work for KSHV and other gammaherpesviruses, as those can remain within the body for a long time.
How the virus does this was unknown until now. The scientists from the HZI research group "Viral Immune Modulation" under the leadership of Prof. Melanie Brinkmann have now been able to show that the virus is actively preventing activation of the innate immune system through Toll-like receptors.
It has yet to be established how exactly and in which part of the Toll-like receptor function is disturbed. This is one of the leverage points for future research: "The better we understand how the virus protects itself from attacks by the immune system, the better we can use this knowledge to fight infections," Brinkmann says.
This may lead to the development of new drugs against gammaherpesviruses. "Those agents could actively protect the immune system and prevent viruses from winning the fight against it," says Bussey. "However, this is still a long way off."
Original publication
Kendra A. Bussey, Elisa Reimer, Helene Todt, Brigitte Denker, Antonio Gallo, Andreas Konrad, Matthias Ottinger, Heiko Adler, Michael Stürzl, Wolfram Brune, and Melanie M. Brinkmann
The gammaherpesviruses KSHV and MHV68 modulate the TLR-induced proinflammatory cytokine response J. Virol. published ahead of print 4 June 2014 , doi:10.1128/JVI.00841-14
The Helmholtz Centre for Infection Research (HZI)
Scientists at the Helmholtz Centre for Infection Research in Braunschweig, Germany, are engaged in the study of different mechanisms of infection and of the body's response to infection. Helping to improve the scientific community's understanding of a given bacterium's or virus' pathogenicity is key to developing effective new treatments and vaccines. http://www.helmholtz-hzi.de
Ideally, our immune system will recognize and subsequently eliminate pathogens that enter our bodies. However, many microorganisms and viruses have evolved strategies to evade immune detection. The "Viral Immune Modulation" research group seeks to uncover the different mechanisms that particularly herpes viruses use to perform this feat.
Journal
Journal of Virology