San Francisco 49ers (4-2) at Denver Broncos (5-1)

Sunday, 8:30 p.m. ET, at Sports Authority Field at Mile High, Denver – TV: NBC

*TV announcers: Al Michaels, Cris Collinsworth, Michele Tafoya

*Keys to the game: The 49ers have recommitted to the ground game during their three-game winning streak, and RB Frank Gore will be heavily involved as San Francisco attempts to slow the game down a bit to protect a defense dealing with Peyton Manning minus several starters. QB Colin Kaepernick is playing at a high level with seven TDs against one interception over the past five games, and it will be incumbent on OLBs DeMarcus Ware and Von Miller to rush the edges with caution so as to limit Kaepernick’s ability to escape the pocket and generate big plays on the move.

The 49ers’ defense is thinned by injuries and OLB Aldon Smith’s suspension, but also motivated not to give up the three touchdowns Manning needs to break Brett Favre’s all-time passing touchdowns record. It’s a tall task, especially with a pair of backup inside linebacker part of the mix attempting to slow TE Julius Thomas, who has a league-leading nine touchdown catches through five games. RBs Ronnie Hillman and Juwan Thompson combined for 138 rushing yards in place of Montee Ball (groin) last week, and production on the ground is vital with the line’s pass protection leaky last week.

*Matchup to watch – 49ers defensive coordinator Vic Fangio vs. Broncos QB Peyton Manning: Manning makes all the calls at the line, and it will be a chess match against Fangio, one of the more creative defensive coordinators in the game. Manning was sacked twice and hit four times by the Jets, and the Broncos began using more two-tight end packages featuring backup OT Paul Cornick.

*Player spotlight – 49ers ILB Chris Borland: The rookie saw his first action of the regular-season after Patrick Willis left Monday’s game with a turf toe injury, and was praised by coach Jim Harbaugh after recording two tackles and breaking up a pair of passes. Diagnosing the action against Manning is an entirely different proposition.

*Fast facts: The 49ers are 15-1 when Kaepernick starts and has a passer rating of 100-plus. … Thomas needs one touchdown catch to become the first Broncos tight end with 10 in consecutive seasons.

WHO WILL WIN AND WHY

The 49ers conclude a tough pre-bye stretch that has included wins over the Eagles, Chiefs and division-rival Rams leading into Sunday night’s trip to Denver, where the Broncos are well-stocked to exploit the 49ers’ defensive injuries.

*Our pick: Broncos 28-27