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Number eight Caelan Doris will captain Ireland for Saturday's second Test against South Africa with usual skipper Peter O'Mahony only among the replacements.
Head coach Andy Farrell has moved Tadhg Beirne to O'Mahony's usual blindside flanker role and brought James Ryan into the second row.
In all Farrell has made four changes to the side that lost the first Test 27-20 in Pretoria last weekend, their first reverse to the Springboks since 2016.
South African head coach Rassie Erasmus had already named an unchanged squad for this weekend's game in Durban.
While Ryan's promotion to the starting side over O'Mahony appears to be a selection decision, Farrell was always going to have to alter his team for what is the last game of a long season.
Scrum-half Craig Casey and hooker Dan Sheehan were both ruled out earlier this week with injuries sustained in the first Test.
The vastly experienced Conor Murray will start at nine with Connacht's Caolin Blade among the replacements.
Ronan Kelleher is promoted into the starting side in place of Sheehan with Ulster's Rob Herring, a Cape Town native, coming onto the bench.
While Bundee Aki was not included in Ireland's injury update, he appeared to be carrying a knock after the defeat at Loftus Versfeld and is not in this weekend's panel.
Instead Robbie Henshaw switches from outside to inside centre with his Leinster colleague Garry Ringrose to wear the 13 jersey.
Resisting the temptation to the 6:2 bench split used during the Six Nations, centre Stuart McCloskey takes Ringrose's place among the replacements.
Ireland: Osborne; Nash, Ringrose, Henshaw, Lowe; Crowley, Murray; Porter, Kelleher, Furlong; McCarthy, Ryan; Beirne, Van der Flier, Doris (capt).
Replacements: Herring, Healy, Bealham, Baird, O'Mahony, Blade, Frawley, McCloskey.