Ion channel activity of influenza A virus M2 protein: characterization of the amantadine block

Abstract

The influenza A virus M2 integral membrane protein has ion channel activity which can be blocked by the antiviral drug amantadine. The M2 protein transmembrane domain is highly conserved in amino acid sequence for all the human, swine, equine, and avian strains of influenza A virus, and thus, known amino acid differences could lead to altered properties of the M2 ion channel. We have expressed in oocytes of Xenopus lwvis the M2 protein of human influenza virus A/Udorn/72 and the avian virus A/chicken/Germany/34 (fowl plague virus, Rostock) and derivatives of the Rostock ion channel altered in the presumed pore region. The pH of activation of the M2 ion channels and amantadine block of the M2 ion channels were investigated. The channels were found to be activated by pH in a similar manner but differed in their apparent Kis for amantadine block.

Influenza and Viral Pneumonia

“…88 The adamantanes, which include amantadine and rimantadine, block the M2 protein, a membrane protein with ion channel activity. 89 They exhibit activity against influenza A but not against influenza B. The antiviral drugs currently approved by the US Food and Drug Administration are the neuraminidase inhibitors oral oseltamivir, inhaled zanamivir, and intravenous peramivir.…”

Towards our understanding of SARS-CoV, an emerging and devastating but quickly conquered virus

“…Third, three accessory proteins have been identified to have roles in apoptosis [66,67,69,71]. Very recently, the 3a protein, a transmembrane protein, was unveiled to function as an ion channel, which might be similar to M2 protein of influenza virus, indicating its possible role in the release and package of mature virus particles [72][73][74]. Also, it can trigger apoptosis in Vero E6 cells, which is supported by in vitro experiments of chromatin condensation and DNA fragmentation [66].…”

Viral channel forming proteins — How to assemble and depolarize lipid membranes in silico

“…In the 90s, proteins which alter membrane permeability were identified for a series of viruses such as 2B and 3A of polio virus [3], 6K protein of Semliki Forest virus [4], M2 of influenza A [5,6] and Vpu of HIV-1 [7,8]. Since then the number of identified and proposed channel proteins has risen (see reviews [9][10][11][12][13][14][15]).…”