Test rookie Andrew Porter will be tasked with anchoring Ireland's scrum against Wales in Dublin in his first Six Nations start.
Rising star Porter will start at tighthead for Ireland, after Tadhg Furlong failed to beat his hamstring injury in time for Saturday's Aviva Stadium clash.
Centre Chris Farrell will also make his first Six Nations start against Warren Gatland's Wales, while Devin Toner starts at lock with Iain Henderson also missing through hamstring trouble.
Porter scrambled from the bench just three minutes into Ireland's 56-19 win over Italy, when Furlong pulled up with his hamstring issue.
The 22-year-old acquitted himself well against the Azzurri, but now faces an entirely different proposition in a serious baptism of Test-match fire for his fifth cap.
Ireland and Leinster have, however, long held high hopes for the physical under-20s graduate, who only made his Test debut in June 2017.
Farrell slots in for Robbie Henshaw, now sidelined for up to four months after a dislocated shoulder.
The former Ulster midfielder won both his Test caps in Ireland's autumn campaign, and will link up with Bundee Aki again, in an inexperienced centre partnership Wales will clearly seek to exploit.
Head coach Joe Schmidt expects both Furlong and Henderson to be fit for Ireland's clash with Scotland in Dublin on March 10.
"Iain was the closer of the two; Iain could probably have played on Saturday," said Schmidt. "But Iain wasn't able to complete training today so we're not going to risk him.
"I just don't think it's worth it with what's coming up and you don't want to put him at risk of further injury. He could definitely play next week, and the week after he will be fine.
"We thought with Tadhg he may well make it, but the progress just stalled a little bit so we said 'let's not chase this, get you right for Scotland in a couple of weeks' time'."
Ireland hosts Wales at Aviva Stadium on Saturday February 23, kicking off at 2:15pm local, Sunday 1:15am AEDT.
1. Cian Healy
2. Rory Best
3. Andrew Porter
4. James Ryan
5. Devin Toner
6. Peter O'Mahony
7. Dan Leavy
8. CJ Stander
9. Conor Murray
10. Johnny Sexton
11. Jacob Stockdale
12. Bundee Aki
13. Chris Farrell
14. Keith Earls
15. Rob Kearney
16. Sean Cronin
17. Jack McGrath
18. John Ryan
19. Quinn Roux
20. Jack Conan
21. Kieran Marmion
22. Joey Carbery
23. Fergus McFadden