Good tips, thanks!
Evidently, and I can not find any documentation of this, the HD500 will only work with "high speed" USB 2.0 "480 Mbit/s (effective throughput up to 35 MB/s or 280 Mbit/s) (now called "Hi-Speed")". I have no idea why it would need so much bandwidth for changing patch settings, and it certainly needs a tiny fraction of that for audio. Evidently it is not capable of falling back/negotiating at older/slower standards. I would love some official confirmation of this, I can't find it documented anywhere. I found some discussion that people who went from XT to X3 found their USB ports were suddenly incompatible. Presumably the HD line continues this, even though there has not been a need for the increased bandwidth since before the XT line.
All usb isolator devices on the market, short of some very expensive (like $1,000+) medical devices or whatever, can only do "full speed" - "USB 1 specified data rates of 1.5 Mb/s (Low-Bandwidth) and 12 Mb/s (Full-Bandwidth)." So the fact that every single USB isolator product claims "full speed" and either USB 2.0 "compliant" or "compatible, it turns out to be misleading, and "full" is slower than "high."
Very unfortunate, since it would solve so many problems that so many people are having. I have to admit I've wondered why Line 6 doesn't think about integrating USB isolation directly into the product, since so many people have so much frustration. It would make it a much more robust product than many of their competitors.
I guess I'll try to another tactic of isolating the HD500 from the guitar amp's input with a transformer. I made a "re-amp" box out of a Jensen transformer in the past, I think a 1:1 transformer will work?
https://www.edcorusa.com/p/80/tpc10k-10k
It only solves the problem of noise/ground loop hum into the guitar amp's input, not the rest of the monitoring/recording system, but at this point the product can not be used for its intended purposes in my system and I might just return it.