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A Single Amino Acid Mutation in the Envelope Cytoplasmic Tail Restores the Ability of an Attenuated Simian Immunodeficiency Virus Mutant To Deplete Mucosal CD4+ T Cells |
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| Authors: | Matthew W Breed Andrea P O Jordan Pyone P Aye Chie Sugimoto Xavier Alvarez Marcelo J Kuroda Bapi Pahar Brandon F Keele James A Hoxie Andrew A Lackner |
| Institution: | Tulane National Primate Research Center, Covington, Louisiana, USAa;Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USAb;SAIC-Frederick, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USAc |
| Abstract: | Disruption of the conserved motif GYxxØ in the simian immunodeficiency virus (SIV) SIVmac239 envelope (Env) cytoplasmic tail resulted in a virus (ΔGY) that exhibited a high plasma peak but uniquely failed to acutely deplete mucosal CD4+ T cells. Here, we show that ΔGY containing a flanking S727P mutation that was acquired in ΔGY-infected macaques reacquired the ability to rapidly deplete CD4+ T cells in lamina propria. This suggests that the GYxxØ motif and S727P each contribute to SIV''s targeting to mucosal tissues. |
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