A source told People that the couple had been living apart for some time while trying to salvage the relationship, but it seems it was all for naught.
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Wilde, 26, and Ruspoli, 35, eloped in Virginia six months after meeting when Wilde was 18. They later had an official wedding.
Ruspoli is a filmmaker based in Los Angeles. His family owns the Palazzo Ruspoli in Rome and a castle in Vignanello, Italy.
The House actress is next set to be seen on the silver screen in two big summer releases: she'll be fighting interstellar visitors alongside Daniel Craig and Harrison Ford in the sci-fi action flick Cowboys & Aliens and getting laughs with Jason Bateman and Ryan Renyolds in The Change Up.