2015
DOI: 10.1016/j.chom.2015.09.003
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Cell Surface Proteomic Map of HIV Infection Reveals Antagonism of Amino Acid Metabolism by Vpu and Nef

Abstract: SummaryCritical cell surface immunoreceptors downregulated during HIV infection have previously been identified using non-systematic, candidate approaches. To gain a comprehensive, unbiased overview of how HIV infection remodels the T cell surface, we took a distinct, systems-level, quantitative proteomic approach. >100 plasma membrane proteins, many without characterized immune functions, were downregulated during HIV infection. Host factors targeted by the viral accessory proteins Vpu or Nef included the ami… Show more

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Cited by 159 publications
(210 citation statements)
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“…The presence of this G2 arrest protein signature indirectly validates our strategy. Taken together, these data indicate that SILAC represents a powerful tool to study rapid large-scale proteomic changes in the cellular environment induced by HIV-1 Vpr, as has been recently demonstrated for other HIV proteins (56). Of note, we also validated our SILAC procedure with the observation that SAMHD1 levels were strongly decreased on delivery of HIV-2/SIVsmm Vpx protein as expected (57,58).…”
Section: Resultssupporting
confidence: 52%
“…The presence of this G2 arrest protein signature indirectly validates our strategy. Taken together, these data indicate that SILAC represents a powerful tool to study rapid large-scale proteomic changes in the cellular environment induced by HIV-1 Vpr, as has been recently demonstrated for other HIV proteins (56). Of note, we also validated our SILAC procedure with the observation that SAMHD1 levels were strongly decreased on delivery of HIV-2/SIVsmm Vpx protein as expected (57,58).…”
Section: Resultssupporting
confidence: 52%
“…By virtue of this adaptor function, Nef affects many central processes in HIV target cells. This includes modulation of cellular transport pathways leading to downregulation of an array of receptors from the surface of infected cells (4)(5)(6), which, e.g., prevents superinfection (7,8) and lysis of productively infected cells by cytotoxic T or NK cells (9,10). HIV-1 Nef also alters the response of CD4 T lymphocytes to stimulation via the T cell receptor (TCR), and modulation of the resulting cellular signaling pathways is thought to increase virus replication in the infected host (11)(12)(13)(14)(15)(16)(17).…”
mentioning
confidence: 99%
“…They include immunoreceptors, such as human leukocyte antigen C (HLA-C) (20), NK-T-B antigen (NTB-A) (21), CD1d (22), and poliovirus receptor (PVR) (23); homing molecules, like CCR7 (24) and CD62L (25); sodium-coupled neutral amino acid transporter 1 (SNAT1) (26); and numerous members of the tetraspanin family (27). These downregulations lead to a wide array of immunomodulatory effects, including immune evasion and metabolic dysfunction.…”
mentioning
confidence: 99%