Well firstly instead of a lore wipe, how about a major event in current lore?
With the advent of nuclear gas clouds somewhere on the horizon, instead of forcing yet another slog through the same tired "new infection" lore. A nuclear plant finally reaching critical mass, the threat to life evolving and the world actually being effected by a progressing event over a long term period. Make the infected important again, stop setting aside the major and underused enemy that are the infected, perhaps evolve the infection, make it something new. I have so many ideas written down I could go on forever.
Just don't throw out what we already have, it's clear it doesn't really work or improve RP.