It's a little different from the X3. The HD500 doesn't have two completely seperate processing channels (Tones), like the X3. The HD500 allows you to create two seperate processing paths in a more flexible manner, and you can share some FX between the paths, in either pre- or post-amp position. But, yes, you can assign different inputs to each part of the split path. The manual actually describes it fairly clearly, but you need to know where to look and how things fit together, especially thi pre- vs. post- positioning of FX and amps. Here's the rundown:

The first part of it is handled in Setup: Input Options. Here you assign which of the physical inputs on the HD500 you want to assign to your two logical inputs.This is explained in the HD500 Advanced Guide, page 2-5. Pay attention to the description of Source Input Signal Routing. The most important piece of that for your purposes, I think, is the following:

In a configuration with no Amp or FX Blocks in Pre, Input 1 is discretely fed to
Path A and Input 2 to Path B. Therefore, this is the best configuration if you want
to retain discrete Input Sources into Paths A & B (such as if your Input 1 is Guitar,
and Input 2 is Aux, Mic or Variax, and you want to apply completely different Amps
and/or FX on each).

The next part is to create a patch that uses the dual paths - A & B - in the routing. This is explained in the  Guide, page 6-1. You select your path routing and place the amps and FX as desired to match your Input selections and the Source Input Signal Routing conventions.

Hope this helps.