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

HIV-1 Nef-mediated T-cell activation and chemotaxis are decoupled using a HIV-1/SIVpbj1.9.... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

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

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Publisher
Springer Vienna
Copyright
Copyright © 2013 by Springer-Verlag Wien
Subject
Biomedicine; Virology; Medical Microbiology; Infectious Diseases
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s00705-012-1560-z
Publisher site
See Article on Publisher Site

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.

Journal

Archives of VirologySpringer Journals

Published: Apr 1, 2013

References

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