Hi Chris.
Have you configured Email Source account as well as Orion?
Does problem appears only with NPM alerts, or with mail integration also?
It looks like in some point of time AC (or your VM) loose connection and can establish it only after reboot.
Also please check reboot of VM, or you can reboot only AC to reproduce this behavior.
Rebooting only AC instance can be done from appliance (https://yourHous:5480). You can login with credentials admin/admin.
Also if it's AC problem, them logbundle would be helpful.
Regards,
Stepan Husak