Abstract
It has previously been shown that the Flavivirus West Nile Virus (WNV) enters the macrophagelike cell line P 388D 1 rapidly on warming to 37°C. Initially particles are internalized in coated vesicles and subsequently appear in endosomes and then lysosomes. WNV particles have been shown to fuse with artificial liposomes optimally at mild acidic pH. In the present study, interaction between WNV and P 388D 1 cells was assayed by following the association of Pronase-resistant 35S-labelled virus with cells. Transmission and Scanning electron microscopy were also used for this purpose. Virus particles were shown to have an increased affinity for the cell structure at pH below 7.0. This was shown to be because virus particles were fusing in a pH-dependent manner with maximum fusion occuring at pH6.4 or below. We have previously showed that lysosomotropic amines can inhibit WNV infection by raising the pH in the endosomal compartments. It is thus probable that acid pH-dependent fusion is important in release of the WNV nuclear capsid from endosome to the cytosol. Radiobinding study and electron microscopy showed that a balance exists between endocytosis and fusion of Flaviviruses with the P 388D 1 cell plasma membrane, with pH of extracellular medium deciding which one predominates.
