So out of the blue my backups started barfing when trying to backup one of my ISA servers. Which really sucks because it was working fine.
V-79-57344-65072 - The connection to target system has been lost. Backup set canceled
The only changes that were made recently were just the application of the latest security patches, etc from MS. (Of course, Symantec's support of ISA with Backup Exec has never been stellar so I can't rule out the possibility that it just stopped working randomly). I went ahead and checked the usual forums, KBs, etc and found a lot of references to the error. I did the usual logging on the ISA server to check the traffic flow, etc and did notice that the agent kept trying to use the external network adapter even though the initial connections were being handled from the internal adapter. For testing I even tried creating a bi directional full access rule between the ISA server and the backup exec server and it didn't fix it. The only thing that worked was to create a User Defined Selection and use that for the backup job definition instead of the server name as mentioned in this forum post here:
I created a new User Defined Selection and used the Internal IP address of that ISA server and the damn thing started working.