Wiese was a late withdrawal from the match against France in Marseille last week and will take over from Kwagga Smith, who will start among the replacements.
Nienaber also handed starts to locks Salmaan Moerat and Marin Orie with Lood de Jager having returned home with a shoulder injury and Eben Etzebeth dropping to the bench.
Andre Esterhuizen comes in at inside centre in a new-look midfield pairing with Damian de Allende, who switches to outside centre in place of Jesse Kriel.
The other positional switch sees Franco Mostert move from lock to flanker in place of Pieter-Steph du Toit, who is awaiting a disciplinary hearing on Wednesday for a red card received against France for cleaning out a ruck dangerously.
No 8 Evan Roos, meanwhile, will feature on the replacements bench alongside forwards Etzebeth, Smith, and the front row of Steven Kitshoff, Vincent Koch (both props) and Malcolm Marx (hooker) in a split of six forwards and two backs on the bench.
Cobus Reinach (scrumhalf) and Manie Libbok (utility back), in turn, will provide backline cover, with Libbok able to cover flyhalf, centre, wing and fullback.
“A couple of players have been training very hard in the last few weeks and deserve a chance to start, and Lood’s injury and Pieter-Steph’s disciplinary hearing opened the door for us to give them an opportunity,” said Nienaber.
“Salmaan and Marvin are both DHL Stormers players, so they have been playing together for a while, and they are very hungry for game time, so we are looking forward to what they bring in the game.
“It’s also good to have Jasper back against the physical Italian pack, and we know that Kwagga will spark something different when he takes the field. Evan also gets a chance off the bench and his skills will work well with Kwagga’s in the loose trio, while Manie earns another run after making his debut last week.
“Manie’s versatility will also come in handy, as he can cover most positions in the backline, and with Cobus on the bench and several experienced backs in the backline, he will have enough guidance to be able play to his game.”
Nienaber expected a passionate performance from Italy, who pipped Australia 30-29 last week in front of a vocal home crowd, and said: “Italy’s victory against Australia will boost their confidence immensely going into this match, and we are expecting them to draw a lot of energy from their home crowd.
“They defeated Wales away in the Six Nations and tested Scotland as well, so we are under no illusions as to the challenge that lies ahead. Italy have shown before what a force they can be at home by defeating the Boks 20-18 in Florence, and they will draw confidence from that as well.
“We have been working hard on improving the areas of the game that let us down in the last two matches, and we are determined to get onto the right side of the scoreboard after very narrow defeats against the first and second ranked teams in the world.”
Zoning in on Italy, Nienaber said: “Their forwards are physical, they have a skillful backline and a good defensive system, and they play with a lot of confidence, so we know what we are in for. We have to deliver a quality performance for the full 80 minutes.
“We believe we are on the right track after coming close against Ireland and France, and if we can produce a strong showing up front and be a little more accurate in our execution, we know we can turn things around on tour.”
Springbok team to face Italy in Genoa:
15 – Willie le Roux (Toyota Verblitz) – 81 caps, 65 pts (13t)
14 – Cheslin Kolbe (Toulon) – 22 caps, 61 pts (10t, 1c, 3p)
13 – Damian de Allende (Wild Knights) – 68 caps, 45 pts (9t)
12 – Andre Esterhuizen (Harlequins) – 10 caps, 0pts
11 – Kurt-Lee Arendse (Vodacom Bulls) – 5 caps, 20 pts (4t)
10 – Damian Willemse (DHL Stormers) – 25 caps, 25 pts (1t, 4c, 4p)
9 – Faf de Klerk (Canon Eagles) – 44 caps, 30 pts (5t, 1c, 1p)
8 – Jasper Wiese (Leicester Tigers) – 19 caps, 5 pts (1t)
7 – Franco Mostert (Honda Heat) – 61 caps, 15 pts (3t)
6 – Siya Kolisi (captain, Cell C Sharks) – 73 caps, 45 pts (9t)
5 – Marvin Orie (DHL Stormers) – 8 caps, 0 pts
4 – Salmaan Moerat (DHL Stormers) – 2 caps, 0 pts
3 – Frans Malherbe (DHL Stormers) – 56 caps, 5 pts (1t)
2 – Bongi Mbonambi (Cell C Sharks) – 53 caps, 55 pts (11t)
1 – Ox Nche (Cell C Sharks) – 17 caps, 0 pts
16 – Malcolm Marx (Kubota Spears) – 57 caps, 65 pts (13t)
17 – Steven Kitshoff (DHL Stormers) – 69 caps, 5 pts (1t)
18 – Vincent Koch (Stade Francais) – 40 caps, 0 pts
19 – Eben Etzebeth (Cell C Sharks) – 108 caps, 15 pts (3t)
20 – Kwagga Smith (Shizuoka Blue Revs) – 29 caps, 15 pts (3t)
21 – Evan Roos (DHL Stormers) – 1 cap, 0 pts
22 – Cobus Reinach (Montpellier) – 22 caps, 40 pts (8t)
23 – Manie Libbok (DHL Stormers) – 1 cap, 0 pts
Springbok record against Italy:
Played 15; Won 14; Lost 1; Points for: 701, Points against: 174; Tries scored 96, Tries conceded 14; Highest score 101-0; Biggest win 101 points. Win % 93%.
- Siya Kolisi is the second most capped Springbok captain having led the side in 43 Test matches.
- Eben Etzebeth is the second most capped Springbok lock with 108 Tests.
- The total Test caps for the Springbok starting line-up is 544.
- There are 255 caps in the backline, with 289 caps among the forwards. On the bench there are a further 327 caps.
- The average caps per player in the backline are 36, the forwards 36, while the players on the bench average 40.