Jonathan Sexton has not recovered in time for Ireland's Six Nations trip to Italy this weekend as he continues to struggle with a calf injury.
The fly-half sustained the problem in Leinster's Champions Cup draw with Castres on January 20.
Although he returned to full training last week, Sexton did not feature as Ireland fell to a 27-22 defeat against Scotland at Murrayfield on Saturday, and he will miss out again in Rome with Joe Schmidt making two changes to his XV.
Donnacha Ryan replaces Iain Henderson - who has a slight hamstring injury - at lock, while the experienced Cian Healy comes in at prop instead of Jack McGrath, who drops to the bench.
"Donnacha is a pretty good line-out operator, he's a good technician in that area and a good tactician too," Schmidt said in Thursday's media conference.
"We're not playing catch-up entirely, that's one of the great things about this championship - as long as we keep getting better we can stay in control of our destiny.
"We're focused on the immediate challenge and trying to do the best we can.
"To get that real certainty you want the more time together you can get. You try to replicate that in training but there's nothing like going out on the pitch and trying to cope."
Ireland starting XV: Rob Kearney, Keith Earls, Garry Ringrose, Robbie Henshaw, Simon Zebo, Paddy Jackson, Conor Murray; Cian Healy, Rory Best (captain), Tadhg Furlong, Donnacha Ryan, Devin Toner, CJ Stander, Sean O'Brien, Jamie Heaslip.
Replacements: Niall Scannell, Jack McGrath, John Ryan, Ultan Dillane, Josh van der Flier, Kieran Marmion, Ian Keatley, Craig Gilroy.