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Getting it against a wounded Ireland will not be easy - Joe Schmidt's side were slow out of the blocks last week against Scotland and know that a second successive defeat would all but end their title hopes.
The Irish looked to have dug themselves out of a hole in Edinburgh when they overcame a 21-8 half-time deficit to lead midway through the second period.
But two Greig Laidlaw penalties left them with just a losing bonus point, and in response Schmidt has made two changes to his team.
Donnacha Ryan comes in for Iain Henderson in the second row, while Cian Healy and Jack McGrath swap roles, the former into the starting team, the latter dropping to the bench.
Italy have made four changes, with the return of influential pair Dries van Schalkwyk, in the second row, and Simone Favaro at openside flanker.
Former skipper Leonardo Ghiraldini is back at hooker, and there's a start on the wing for Angelo Esposito.
Most crucially, O'Shea will be delighted to have seen Sergio Parisse come through a fitness test to lead the team.
Click here for the complete 2017 RBS 6 Nations fixture list with TV schedule
Conor O'Shea (Italy): "Ireland is my home, my family, it's the place where we spend the holidays. It's the country where I grew up and where I always wanted to play.
"But now my only objective is Italian rugby. So I don't think of Ireland but only of us, Italy.
"We face a mountain to climb for 80 minutes, so I hope we're ready for a big game this weekend."
Joe Schmidt (Ireland): "I would have had a lot of discussions with Conor about coaching.
"We trained with Harlequins in the World Cup which was great fun and great preparation.
"I think Conor got a good look at how we train and what we try to do. He potentially can use that to his advantage now."
Simone Favaro v Sean O'Brien:
Named Glasgow Warriors' Player of the Season last year, Simone Favaro's return is a huge boost for Italy for the remainder of the Championship.
He will go up against Sean O'Brien, and be charged with tackling everything in sight with his usual relentless work-rate.
#ITAvIRE è domani all'Olimpico e dalle 14.45 su @dmaxitalia#Italrugby, mai paura! pic.twitter.com/mqPwGrIw1p
- Italrugby (@Federugby) February 10, 2017
O'Brien played his part for Ireland in Edinburgh, carrying with intent and getting involved at the breakdown to try and slow down Scotland ball. But he will hope to make even more of an impact in Rome, alongside CJ Stander and Jamie Heaslip.
Stat watch:
Conor O'Shea faced Italy twice in his playing career for Ireland. Both games were in Dublin at Lansdowne Road - losing in 1997 and earning a measure of revenge with victory in 1999, a game in which he scored two tries.
The Italians have not won in Rome since 2013 - with their last win at the Stadio Olimpico coming against Ireland in Declan Kidney's final season in charge.
Fantasy Watch:
Click here to play the 2017 RBS 6 Nations Fantasy Game
Only goal-kicker Paddy Jackson scored more points for Ireland on the opening weekend than Rob Kearney, and the full-back could be one to watch once more in Rome.
From an Italian perspective, while Parisse was brilliant in the first half, the incredible tackle numbers of Maxime Mbanda - racking up 26 in total - making him an intriguing fantasy option.
Italy v Ireland
11 February
Stadio Olimpico
Kick-off:15:25 (local)
TV: DMAX, RTE, ITV, FR2, BBC (H)
