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Replicative fitness of transmitted HIV-1 drives acute immune activation, proviral load in memory CD4 + T cells, and disease progression

2015; National Academy of Sciences; Volume: 112; Issue: 12 Linguagem: Inglês

10.1073/pnas.1421607112

1091-6490

Daniel T. Claiborne, Jessica Prince, Eileen P. Scully, Gladys Macharia, Luca Micci, Benton Lawson, Jakub Kopycinski, Martin J. Deymier, Thomas H. Vanderford, Krystelle Nganou‐Makamdop, Zachary Ende, Kelsie Brooks, Jianming Tang, Tianwei Yu, Shabir Lakhi, William Kilembe, Guido Silvestri, Daniel C. Douek, Paul Goepfert, Matt A. Price, Susan Allen, Mirko Paiardini, Marcus Altfeld, Jill Gilmour, Eric Hunter,

Immune Cell Function and Interaction

Significance HIV infection is associated with elevated inflammation and aberrant cellular immune activation. Indeed, the activation status of an HIV-infected individual is often more predictive of disease trajectory than viral load. Here, we highlight the importance of the replicative fitness of the transmitted viral variant in driving an early inflammatory state, characterized by T-cell activation and immune dysfunction. This impact on T-cell homeostasis is independent of protective host immune response genes and viral load. Highly replicating transmitted variants were also significantly more efficient at infecting memory CD4 + T cells, a population important for maintaining the latent viral reservoir. Together, these data provide a mechanism whereby viral replicative fitness acts as a major determinant of disease progression and persistence.