Journal of virology 2017 07 05() pii 10.1128/JVI.00352-17
Progressive T cell depletion during chronic human immunodeficiency virus (HIV) infection is a key mechanism that leads to the development of AIDS. Recent studies have suggested that most T cells in the tissue die through pyroptosis triggered by abortive infection, i.e. infection of resting T cells where HIV failed to complete reverse transcription. However, the contribution of abortive infection to T cell loss and how quickly abortively infected cells die in vivo, key parameters for a quantitative understanding of T cell population dynamics, are not clear. Here, we infected rhesus macaques with simian-human immunodeficiency viruses (SHIV) and followed the dynamics of both plasma SHIV RNA and total cell-associated SHIV DNA. Fitting mathematical models to the data, we estimate that upon infection a majority of CD4(+) T cells become abortively infected (approximately 65% on average) and die at a relatively fast rate of 0.27 day(-1) (half-life: 2.6 days). This confirms the importance of abortive infection in driving T cell depletion. Further, we find evidence suggesting that an immune response maybe restricting viral infection 1-3 weeks after infection. Our study serves as a step-forward towards a quantitative understanding of the mechanisms driving T cell depletion during HIV infection.IMPORTANCE In HIV infected patients, progressive CD4(+) T cell loss ultimately leads to the development of AIDS. The mechanisms underlying this T cell loss are not clear. Recent experimental data suggests that the majority of CD4(+) T cells in tissue die through abortive infection where accumulation of incomplete HIV transcripts triggers cell death. To investigate the role of abortive infection in driving CD4(+) T cell loss in vivo, we infected macaques with a simian-human immunodeficiency viruses (SHIV) and followed the viral kinetics of both plasma RNA and cell-associated DNA during infection. Fitting mathematical models, we estimated that a large fraction of infected cells die through abortive infection and have a half-life of approximately 2.6 days. Our results provide the first in vivo quantitative estimates of parameters characterizing abortive infection and supports the notion that abortive infection represents an important mechanism underlying progressive CD4(+) T cell depletion in vivo.