IMPORTANCEIn this paper, we define that HIV-1 Nef and Vpu display a surprising functional overlap and affect the cell surface exposure of a previously unexpected breadth of cellular receptors. Our analyses furthermore identify the tetraspanin protein family as a previously unrecognized target of Nef and Vpu activity. These findings have implications for the interpretation of effects detected for these accessory gene products on individual host cell receptors and illustrate the coevolution of Nef and Vpu function.
This work was supported by Deutsche Forschungsgemeinschaft Grants FA378/10-2 and SFB1129 (to O.T.F.) and SFB1129 (to M.T.), and the Nakatani Foundation (to M.T.). N. Tsopoulidis was supported by a Heidelberg Biosciences International Graduate School fellowship. O.T.F. and M.T. are members of the CellNetworks Cluster of Excellence (EXO81). O.T.F. designed the study, interpreted results, and wrote the manuscript together with B.S. M.L.-M. conducted and analyzed the experiments shown in Figs. 1-3 and 5. S.K. conducted and analyzed the in vivo homing experiments. B.S. carried out the transendothelial migration experiments together with R.L., conducted the Seahorse analyses with help from J.W. and G.C., and analyzed the data. N. Tsopoulidis recorded the movies analyzed in Figs. 4 and 5. J.T. and M.T. generated and interpreted the power spectrum analyses (Fig. 4B-G).
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