Scotland centre Alex Dunbar will be sidelined for up to nine months after rupturing the anterior cruciate ligament in his knee, the Scottish Rugby Union (SRU) announced on Thursday.
The 24-year-old Glasgow player sustained the injury during training as Scotland prepared for their Six Nations encounter with England at Twickenham on Saturday, in which he was due to start.
A subsequent hospital scan revealed the extent of the damage, ruling Dunbar out of the rest of the season and seriously jeopardising his chances of competing in this year's World Cup in England, which starts in September.
Speaking before the extent of Dunbar's injury had been confirmed, Scotland head coach Vern Cotter said: "Alex was in a bit of discomfort. He just went down on his own. It was a change of direction and then he went down."
Cotter announced five changes in all for the penultimate match.
David Denton, Dougie Fife Jim Hamilton and Finn Russell also return for Scotland, who are desperate for victory following successive losses to France, Wales and Italy.
The others out injured are Johnnie Beattie, Sean Lamont, Tim Swinson and Peter Horne.
"Jim comes in and will bring his physicality and understanding of English rugby to our forward pack," Cotter said in a statement released by Scottish Rugby.
"It's good to have Dave Denton back as he provides us with strong ball-carrying and strong defence. He's also a very good line-out forward and will give us a bit more physical density against a big forward pack.
"It's been tough on Finn to sit out (due to suspension) and it's great to have him back. He's slotted straight back in to the structure we're looking for.
"Finally, Dougie came on and played well against France and has had a couple of games with his club with a few work-ons.
"We're looking for him to bring his enthusiasm, energy and high work-rate, particularly in kick-chase and receipt."
Edinburgh number eight Denton is the only player not to have played in the Six Nations so far and replaces Beattie after recovering from a calf strain.
His Edinburgh club-mates Fife and Scott will both be making their first starts of the tournament.
Scott was drafted onto the starting XV after Dunbar succumbed to a knee injury in training on Thursday morning that saw him undergo a hospital scan.
Russell takes over from Peter Horne following a two-week suspension, while Hamilton replaces Swinson.
Scotland (15-1)
Stuart Hogg, Dougie Fife, Mark Bennett, Matt Scott, Tommy Seymour; Finn Russell, Greig Laidlaw (capt); David Denton, Blair Cowan, Robert Harley; Jonny Gray, Jim Hamilton; Euan Murray, Ross Ford, Alasdair Dickinson
Replacements: Fraser Brown, Ryan Grant, Geoff Cross, Tim Swinson, Johnnie Beattie, Adam Ashe, Sam Hidalgo-Clyne, Greig Tonks
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