EDIT: Why do you consider Brain the first signifiant virus to appear? Elk Cloner was the first virus to spread outside of a lab. And both Wabbit and Creeper came much earlier than both. EDIT: For continuity, Elk Cloner not being listed, none of these is the answer.

EDIT : once again , a vague and disturbing question... well , the first virus targeting boot sector of IBM PC systems in 1986 was "Brain". But in that case, the question is not really clear stating that "it's the first virus of significance" as it's obviously not (and I agree about Elk Cloner). Well... another unclear question....