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The southern franchise has been boosted by the absence of a key man for the home side for the match, which kicks off early tomorrow morning New Zealand time.
The Lions have named a strong team but will be without captain and No8 Warren Whiteley, who has a bruised knee.
His absence will be a blow for the home team as the Springbok is a quality player.
However the Lions have the luxury of bringing in super substitute Marnus Schoeman from the bench. He is a player who pops up all over the park and has the ability to turn the ball over.
Kwagga Smith goes to the back of the scrum, replacing Whiteley. Smith is a vastly experienced sevens players, having made more than 150 appearances for the South African sevens side. He is a livewire and physical player, who gets around the field.
The battle in the loose forwards is bound to be rugged and Shannon Frizell, Luke Whitelock and Dillon Hunt will have to be on form. The Lions are second-best in the competition for winning turnovers but are also one of the worst in conceding turnovers.
Highlanders coach Aaron Mauger said the side had travelled well to Johannesburg and was in good shape for the match.
"We have put some plans in place around the way we play the game and we have trust in our bench to do the job. The Lions as a side like to hold on to the ball but that means a lot of opportunities for us if we can get our game right," Mauger said.
Players had to treasure the ball and make the most of chances when they came along.
With four games to go and a crowded table, every game for the Highlanders is going to count.
Mauger said they were simply concentrating on what they could do and not worrying about other games. They had shown some good parts of their game and were just after a bit of polish to finish it off.
He was confident players would be fit enough and tough enough to last the match.
Though the Lions like to move the ball, they can also lean on their set piece when things get tight.
Discipline will be a key for the Highlanders, as will their defensive lineout.
Mauger said after playing under the roof at Forsyth Barr Stadium, the Highlanders should have little issue with the game being played on a fast and hard track at Johannesburg. Fine weather is forecast for the game which is being played mid afternoon.
Interestingly, the past 10 games between the sides have been won alternately. Going on that guide it is the turn of the Lions to be victorious.
Johannesburg, tomorrow, 1.05am
Highlanders: Matt Faddes, Jordan Hyland, Rob Thompson, Tei Walden, Sio Tomkinson, Josh Ioane, Aaron Smith, Shannon Frizell, Dillon Hunt, Luke Whitelock
(captain), Tom Franklin, Josh Dickson, Tyrel Lomax, Liam Coltman, Ayden Johnstone. Reserves: Ash Dixon, Daniel Lienert-Brown, Siate Tokolahi, Jack Whetton,
James Lentjes, Kayne Hammington, Daniel Hollinshead, Waisake Naholo.
Lions: Andries Coetzee, Courtnall Skosan, Lionel Mapoe, Harold Vorster, Aphiwe Dyantyi, Elton Jantjies, Ross Cronje, Kwagga Smith, Cyle Brink, Marnus Schoeman, Marvin Orie, Stephan Lewies, Carlu Sadie, Malcolm Marx (captain), Dylan Smith. Reserves: Jan-Henning Campher, Sti Sithole, Johannes Jonker, Vincent Tshituka, Hacjivah Dayimani, Nic Groom, Shaun Reynolds, Tyrone Green.
Referee: Rasta Rasivhenge (South Africa)