TY - JOUR
T1 - HIV-1 Nef-mediated T-cell activation and chemotaxis are decoupled using a HIV-1/SIVpbj1.9. chimeric nef variant
AU - Park, In Woo
AU - He, Johnny J.
N1 - Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2013/4
Y1 - 2013/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84876057337&partnerID=8YFLogxK
U2 - 10.1007/s00705-012-1560-z
DO - 10.1007/s00705-012-1560-z
M3 - Article
C2 - 23224761
AN - SCOPUS:84876057337
SN - 0304-8608
VL - 158
SP - 845
EP - 852
JO - Archives of Virology
JF - Archives of Virology
IS - 4
ER -