Craig Casey and Ross Byrne will make their first Six Nations starts for Ireland when they travel to Rome to face Italy on Saturday.
With Johnny Sexton out with a groin injury and Conor Murray dropped to the bench, Casey and Byrne will pair at half-back as coach Andy Farrell makes six changes to the team that beat France last time out.
Ronan Kelleher replaces Rob Herring at hooker, while Jack Conan comes in for Peter O'Mahony and Bundee Aki earns a start after coming off the bench in the first two games, replacing Stuart McCloskey.
Dan Sheehan is fit again and has been named among the replacements.
James Ryan will captain the side in Sexton's absence as Ireland look to make it three wins from three following victories against Wales and France.
Ireland have won 22 of their previous 23 matches against Italy in the Six Nations, including the last nine in a row, with their only defeat in that spell coming in Rome in 2013, which was the last time Italy won at home in the competition against anyone.
Italy have made three changes from the side that lost to England in their last game, with fly-half Paolo Garbisi back in for Tommaso Allan.
Coach Kieran Crowley has also recalled Pierre Bruno to the left wing, while Simone Ferrari is in for Marco Riccioni at tighthead prop.
Italy XV: Ange Capuozzo, Edoardo Padovani, Juan Ignacio Brex, Tommaso Menoncello, Pierre Bruno, Paolo Garbisi, Stephen Varney; Danilo Fischetti, Giacomo Nicotera, Simone Ferrari, Niccolo Cannone, Federico Ruzza, Sebastian Negri, Michele Lamaro (c), Lorenzo Cannone.
Replacements: Luca Bigi, Federico Zani, Marco Riccioni, Edoardo Iachizzi, Giovanni Pettinelli, Alessandro Fusco, Luca Morisi, Tommaso Allan
Ireland XV: Hugo Keenan, Mack Hansen, Garry Ringrose, Bundee Aki, James Lowe, Ross Byrne, Craig Casey; Andrew Porter, Ronan Kelleher, Finlay Bealham, Iain Henderson, James Ryan (c), Caelan Doris, Josh van der Flier, Jack Conan.
Replacements: Dan Sheehan, Dave Kilcoyne, Tom O'Toole, Ryan Baird, Peter O'Mahony, Conor Murray, Jack Crowley, Stuart McCloskey.