Thompson, Carol Ann; (1994) The function of the influenza A virus M2 protein. Doctoral thesis (Ph.D), UCL (University College London).

Text out.pdf Download (9MB)

Abstract

The influenza A virus M2 protein is a 70kDa transmembrane protein which forms an ion permeable channel. The specific inhibition of M2 by the antiviral drug amantadine has identified two roles of the protein, in virus uncoating and in the maturation of haemagglutinin (HA). With respect to the latter M2 has been shown to have the ability to modify pH. Immunofluorescence studies using monoclonal antibodies specific for the native and low pH forms of HA showed that the inhibition of M2 causes a pH-induced conformational change in HA within the trans-Golgi or trans-Golgi network (TGN). Consistent with its role in modifying the pH of transport vesicles transfering native HA to the cell surface, M2 was found to colocalize with both conformations of HA. In view of the pH changes observed within the vesicles of the transport pathway, the pH of the cell cytoplasm was studied directly using the fluorescent pH probe SNARF-1. Influenza virus infection was shown to reduce the pH of the cell cytoplasm. At 6 hours p.i. a 0.4pH unit difference was observed between the pH of uninfected and Rostock virus-infected MDCK cells, which effectively abolished the pH gradient across the plasma membrane. The change in cytoplasmic pH was shown to be M2-dependent by its specific reversal by amantadine and inhibition by antiserum against the exposed N-terminus of M2. Similar M2-induced changes in pH were also observed in M2-expressing MEL cells. Further evidence suggests that M2 located in the plasma membrane is responsible for these effects. In addition to its role in modifying the pH within the transport pathway, these studies show that M2 can also affect the pH of the cell cytoplasm, in a manner which is consistent with the transfer of protons.

Download activity - last month

Export as JSONXMLCSV

Download activity - last 12 months

Export as CSVXMLJSON

Downloads by country - last 12 months

Export as XMLCSVJSON

Archive Staff Only

View Item