Uploading via USB/Serial uses the bootloader, it does not erase the bootloader in the process.
Uploading via ISP will always erase the bootloader - the only way an ISP programmer can erase the flash is do do a chip erase operation, which erases the entire flash (and the EEPROM unless EESAVE fuse is programmed). So, if you want to continue being able to program via serial when you do an upload via ISP, you must use the version of the .hex with the bootloader included.