Many viral infections are nipped in the bud by the innate
immune response. This involves specific proteins within the infected
cell that recognize the virus and trigger a signalling cascade -- the
so-called interferon response. This activates a protective mechanism in
neighbouring cells and often results in the death of the primarily
infected cell.
In plants and invertebrates another mechanism is known to function in antiviral immune response: the so-called RNA interference (RNAi) pathway. RNAi uses an intermediate of the viral proliferation process to build a weapon against the virus. Although RNAi also exists in mammals, researchers have until now thought it to be involved in other cellular processes required for gene regulation but not in antiviral immunity. Evidence that RNAi does indeed contribute to mammalian antiviral defence is now published in Science by Olivier Voinnet, professor for RNA biology at ETH Zurich, and his colleagues.
Small interfering RNAs as specific antiviral weapons
The researchers infected mouse embryonic stem cells with two viruses, the encephalomyocarditis virus (EMCV) and the Nodamura virus (NoV). Subsequently, they were able to detect short RNA molecules of about 22 nucleotides in length within the cells. The sequence of these RNA clearly corresponded to the viral genome and they displayed all the characteristics of the main effector molecules of RNAi called the small interfering or siRNAs. This provided evidence that the virus infection had activated the RNAi machinery of mammalian cells.
The trigger for RNAi is an unusual RNA molecule that arises when the viral genome is copied: a long, double-stranded RNA molecule. This double-stranded RNA is cut into shorter pieces to produce siRNAs, which subsequently serve as a homing device. Since they are derived from the viral RNA and thus correspond perfectly to its sequence, they guide molecular scissor proteins to the viral RNA. The latter is subsequently cut into harmless pieces. Thus, the virus can no longer proliferate.
In plants and invertebrates another mechanism is known to function in antiviral immune response: the so-called RNA interference (RNAi) pathway. RNAi uses an intermediate of the viral proliferation process to build a weapon against the virus. Although RNAi also exists in mammals, researchers have until now thought it to be involved in other cellular processes required for gene regulation but not in antiviral immunity. Evidence that RNAi does indeed contribute to mammalian antiviral defence is now published in Science by Olivier Voinnet, professor for RNA biology at ETH Zurich, and his colleagues.
Short RNA molecules are at the center of an antiviral response that has now been confirmed to exist in mammals.
Small interfering RNAs as specific antiviral weapons
The researchers infected mouse embryonic stem cells with two viruses, the encephalomyocarditis virus (EMCV) and the Nodamura virus (NoV). Subsequently, they were able to detect short RNA molecules of about 22 nucleotides in length within the cells. The sequence of these RNA clearly corresponded to the viral genome and they displayed all the characteristics of the main effector molecules of RNAi called the small interfering or siRNAs. This provided evidence that the virus infection had activated the RNAi machinery of mammalian cells.
The trigger for RNAi is an unusual RNA molecule that arises when the viral genome is copied: a long, double-stranded RNA molecule. This double-stranded RNA is cut into shorter pieces to produce siRNAs, which subsequently serve as a homing device. Since they are derived from the viral RNA and thus correspond perfectly to its sequence, they guide molecular scissor proteins to the viral RNA. The latter is subsequently cut into harmless pieces. Thus, the virus can no longer proliferate.
