The siblings Jonathan "Pyro" Mireu and Jessica Mireu team up with Isaac Zivaku in the mission to Virmire during the original Mass Effect game, also known as Mass Effect 1. Aside from some residual animosity from Jessica concerning Isaac, the plans go reasonably well. Due to quick planning from Isaac, the Interferences remain under the radar for most of the mission before being found out through the interrogation with Sovereign, the Reaper vanguard. The Interferences' guts earn them the friendship and respect of Urdnot Wrex, along with that of Garrus Vakarian, and more planning and quick thinking leads to the rescue and survival of not only Captain Kirrahe of the salarian special task groups, but also both Lieutenant Kaidan Alenko and Gunnery Chief Ashley Williams by way of splitting up the group to have Isaac and Pyro save Alenko at the nuclear bomb site, while Jessica worked with Commander Shepard and his team at the site of the defense turrets to save Williams and Kirrahe's team. Due to their valor, these three are awarded honorary Normandy crew status, essentially a way for them to have their own trust relationship with the crew from there on in.

The only avoidable casualty of the scenario is Rana Thanoptis, who is shot and killed by Isaac in order to make sure she is not an issue in the future.

Although the Shepard of the scenario is male, there is a female one in later scenarios due to the botched cloning efforts of Cerberus. The clone is a male one, while the female is a red-haired one and the original Shepard.