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Updated: Jan 11, 2026

A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses
Published on: August 31, 2014
Parallel HIV-1 fitness landscapes shape viral dynamics in humans and macaques that develop broadly neutralizing
Kai S Shimagaki1,2, Rebecca M Lynch3, John P Barton1,2
1Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States.
Abstract:
HIV-1 evolves within individual hosts to escape adaptive immune responses while maintaining its capacity for replication. Coevolution between HIV-1 and the immune system generates extraordinary viral genetic diversity. In some individuals, this process also results in the development of broadly neutralizing antibodies (bnAbs) that can neutralize many viral variants, a key focus of HIV-1 vaccine design. However, a general understanding of the forces that shape virus-immune coevolution within and across hosts remains incomplete. Here, we performed a quantitative study of HIV-1 evolution in humans and rhesus macaques, including individuals who developed bnAbs. We observed strong selection early in infection for mutations affecting HIV-1 envelope glycosylation and escape from autologous strain-specific antibodies, followed by weaker selection for bnAb resistance. The inferred fitness effects of HIV-1 mutations in humans and macaques were remarkably similar. Moreover, we observed a striking pattern of rapid HIV-1 fitness gains that precedes the development of bnAbs. Our work highlights strong parallels between infection in rhesus macaques and humans, and it reveals a quantitative evolutionary signature of bnAb development.
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