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Researchers from EMBL Grenoble have, for the first time, observed different functional states of the influenza virus polymerase as it is actively transcribing. These results, published in Nature Structural & Molecular Biology, provide valuable information for the next generation of anti-influenza drugs.
When a virus infects and enters a host cell, the genomic material in the virus is both replicated to produce multiple copies of itself and transcribed into viral messenger RNA (mRNA). The viral mRNA can be read by the host cell's protein production machinery, tricking it into making viral proteins. The viral proteins package the copies of the viral genome to make progeny viruses that are released from the cell to infect new hosts. An enzyme called a polymerase is responsible for both the transcription and replication of the viral genome and is therefore crucial to the successful propagation of the virus. The influenza virus, with genomic material made of RNA rather than DNA, is no exception to this modus operandi.
Mechanisms - Transcription - Replication - Virus - Spread
"Studying and understanding the unique mechanisms of transcription and replication used by influenza virus is essential to fight its spread," explains EMBL group leader Stephen Cusack.
Stephen Cusack and his research group at EMBL Grenoble started to work on influenza polymerase more than 20 years ago. In 2014, the group published the first crystal structures of the complete polymerase machine. However, attempts to structurally characterize the different states of actively transcribing influenza polymerase have so far been unsuccessful.
Studies - Resting - Structure - Polymerase - Machine
"All studies so far have looked at the resting structure of the polymerase machine; we've never observed it actually doing anything," says Tomas Kouba, a postdoc in the group who, together with Petra Drncová, carried out...
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