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HIV-1 Nef-mediated T-cell activation and chemotaxis are decoupled using a HIV-1/SIVpbj1.9. chimeric nef variant

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Abstract

HIV-1 Nef is known to activate CD4+ T cells but inhibit their migration toward SDF-1α. However, it is not clear how this protein orchestrates these two seemingly concomitant events. In this study, by comparing these two activities of HIV-1 Nef with those of its primate counterpart, SIVpbj1.9, we found that HIV-1 Nef activated T cells only in the presence of CD3/ CD28 stimulation, while SIVpbj1.9 Nef did even without CD3/CD28. We also observed that HIV-1 Nef inhibited T-cell chemotaxis toward SDF-1α, while SIVpbj1.9 Nef did not. A hybrid between HIV-1 and SIVpbj1.9 Nef completely abrogated the chemotaxis blockade by HIV-1 Nef while failing to activate T cells without CD3/CD28 co-stimulation. Mutations in the myristoylation and SH3-binding site, but not the basic-rich domain, in Nef were unresponsive to CD3/CD28 stimulation but reversed the inhibition of migration. These findings indicate that the signals for T-cell activation by Nef do not necessarily parallel those for T-cell migration.

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Authors and Affiliations

  1. Department of Cell Biology and Anatomy, Graduate School of Biomedical Sciences, University of North Texas Health Science Center, CBH-316, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107, USA

    In-Woo Park & Johnny J. He

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Correspondence to In-Woo Park.

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Park, IW., He, J.J. HIV-1 Nef-mediated T-cell activation and chemotaxis are decoupled using a HIV-1/SIVpbj1.9. chimeric nef variant. Arch Virol 158, 845–852 (2013). https://doi.org/10.1007/s00705-012-1560-z

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  • DOI: https://doi.org/10.1007/s00705-012-1560-z

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