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Efficient SIVcpz replication in human lymphoid tissue requires viral matrix protein adaptation
Frederic Bibollet-Ruche, … , Beatrice H. Hahn, Frank Kirchhoff
Frederic Bibollet-Ruche, … , Beatrice H. Hahn, Frank Kirchhoff
Published May 1, 2012; First published April 16, 2012
Citation Information: J Clin Invest. 2012;122(5):1644-1652. https://doi.org/10.1172/JCI61429.
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Categories: Research Article Virology

Efficient SIVcpz replication in human lymphoid tissue requires viral matrix protein adaptation

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Abstract

SIVs infecting wild-living apes in west central Africa have crossed the species barrier to humans on at least four different occasions, one of which spawned the AIDS pandemic. Although the chimpanzee precursor of pandemic HIV-1 strains must have been able to infect humans, the capacity of SIVcpz strains to replicate in human lymphoid tissues (HLTs) is not known. Here, we show that SIVcpz strains from two chimpanzee subspecies are capable of replicating in human tonsillary explant cultures, albeit only at low titers. However, SIVcpz replication in HLT was significantly improved after introduction of a previously identified human-specific adaptation at position 30 in the viral Gag matrix protein. An Arg or Lys at this position significantly increased SIVcpz replication in HLT, while the same mutation reduced viral replication in chimpanzee-derived CD4+ T cells. Thus, naturally occurring SIVcpz strains are capable of infecting HLTs, the major site of HIV-1 replication in vivo. However, efficient replication requires the acquisition of a host-specific adaptation in the viral matrix protein. These results identify Gag matrix as a major determinant of SIVcpz replication fitness in humans and suggest a critical role in the emergence of HIV/AIDS.

Authors

Frederic Bibollet-Ruche, Anke Heigele, Brandon F. Keele, Juliet L. Easlick, Julie M. Decker, Jun Takehisa, Gerald Learn, Paul M. Sharp, Beatrice H. Hahn, Frank Kirchhoff

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Figure 1

Evolutionary relationships of HIV-1 (including groups M, N, O, and P), SIVcpzPtt (upper clade) and SIVcpzPts (lower clade), and SIVgor Gag protein sequences, shown in red, blue, and green, respectively.

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Evolutionary relationships of HIV-1 (including groups M, N, O, and P), S...
The 4 molecular clones of SIVcpz analyzed in this study are highlighted in yellow. The tree was constructed using maximum likelihood methods *Bootstrap support of greater than 80%. Scale bar: 0.1 amino acid replacements per site.
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