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Wingers Rosko Specman and Aphelele Fassi will debut for South Africa as the world champions play for the first time since November 2019 when they meet Georgia in Pretoria on Friday.
The coronavirus pandemic has sidelined the Springboks after they defeated England convincingly in Japan to win the Rugby World Cup a record-equalling third time.
Only six of the team that started against the English were included in the run-on team to face the Georgians in the first international of a two-Test series, with Johannesburg hosting the second on July 9.
Many of the victorious 2019 squad are being rested. Others like number eight Duane Vermeulen are injured, some are recovering from positive Covid-19 tests while prop Tendai 'The Beast' Mtawarira has retired.
"We believe we have a good balance with a number of experienced campaigners and a few young players who have made a strong statement this season," said coach Jacques Nienaber.
"We are also excited to see what the uncapped players bring to the table after impressive performances for their franchises in the last few seasons.
"Each one of them has proved that they deserve an opportunity at this level, and the commitment and enthusiasm they displayed at training has been striking.
"We are expecting Georgia to come out guns blazing with their passionate and physical rugby, so we need to find our rhythm early on and build up a good 80-minute performance.
"We know how big this challenge will be, but it is vital that we build a solid foundation in the next two Tests in order to refine our skill set, match readiness and ability to perform under pressure."
The matches are part of the South African preparations for three Tests against the British and Irish Lions on July 24 in Cape Town and on July 31 and August 7 in Johannesburg.
A 37-strong Lions squad arrived in Johannesburg on Monday and will play four franchises and a South Africa A selection before tackling the Springboks.
Fassi is considered one of the most exciting backline prospects in South Africa while playing mostly at full-back for the Durban-based Sharks.
Number eight Jasper Wiese, who has earned rave reviews for his performances with English outfit Leicester Tigers, is among the eight replacements and will win his first cap if he comes off the bench.
The Pretoria Test will mark the debut of Nienaber as head coach -- he was in charge of defence tactics when South Africa triumphed in Japan under Rassie Erasmus.
Erasmus has since returned to his original role of national director or rugby, but will assist Nienaber in squad preparations and on match days.
South Africa and European second-tier rugby nation Georgia have met only once with the Springboks winning 46-19 in a 2003 World Cup group match in Australia.
Willie le Roux; Rosko Specman, Jesse Kriel, Francois Steyn, Aphelele Fassi; Handre Pollard, Cobus Reinach; Kwagga Smith, Pieter-Steph du Toit, Siya Kolisi (capt); Franco Mostert, Eben Etzebeth; Trevor Nyakane, Bongi Mbonambi, Ox Nche
Replacements: Malcolm Marx, Steven Kitshoff, Frans Malherbe, Marvin Orie, Jasper Wiese, Herschel Jantjies, Elton Jantjies, Damian Willemse
Coach: Jacques Nienaber (RSA)