Proton channels of influenza A and B viruses

Influenza A and B viruses are enveloped negative strand RNA viruses that contain eight RNA segments. Segment 7 encodes the M1 protein and a proton channel protein (A/M2 for influenza A virus, BM2 for influenza B virus). A/M2 and BM2 proteins have very different amino sequences, except they share a common motif, HXXXW, in their transmembrane domain, which is essential for channel activation and gating. Channel activities of A/M2 and BM2 proteins are essential to virus replication. A/M2 protein is also the target of the adamantane class of drugs (amantadine and its analog compound rimantadine); one of two antiviral drugs against influenza A virus, whereas the BM2 protein is not inhibited by amantadine. Since the identification of the A/M2 protein in 1981, it has been extensively studied by mutagenesis, electrophysiology, and numerous structural studies, such as CD, fluorescence, solid state nuclear magnetic resonance (NMR), solution NMR, and X-ray crystallography. In this chapter, we focus on A/M2 protein to discuss recent advances in structure-function studies and the mechanism for drug inhibition. Finally, ongoing studies to develop an antiviral drug against the currently circulating form of the A/M2 protein are summarized.