Proteomics

Dataset Information

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Probing the HIV-Host Interactome in Infected Cells


ABSTRACT: Although genetically compact, HIV-1 commandeers vast arrays of cellular machinery that sustain and protect it during cycles of viral outgrowth. Transposon-mediated saturation linker scanning mutagenesis was used to isolate fully replication-competent viruses harboring a potent foreign epitope tag. Using these viral isolates, we performed differential isotopic labeling and affinity-capture mass spectrometric analyses on samples obtained from cultures of human lymphocytes to classify the vicinal interactomes of the viral Env and Vif proteins as they occur during natural infection. Importantly, interacting proteins were recovered without bias, regardless of their potential for positive, negative or neutral impact on viral replication. Specific host associations made with trimerized Env during its biosynthesis, at virological synapses, with innate immune effectors and with certain cellular signaling pathways (ex. Notch1) were identified. We also defined Vif associations with host proteins involved in the control of nuclear transcription and nucleoside biosynthesis as well as those that interact both stably and transiently with the cytoplasmic protein degradation apparatus. Our approach is broadly applicable to elucidating pathogen-host interactomes, providing high certainty identification of interactors by their direct access during cycling infection. Understanding the pathophysiological consequences of these associations is likely to provide strategic targets for antiviral intervention.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell

DISEASE(S): Human Immunodeficiency Virus Infectious Disease

SUBMITTER: Todd Greco  

LAB HEAD: Ileana Cristea

PROVIDER: PXD003762 | Pride | 2016-07-06

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
2010_11_uniprotS_human_hiv.fasta Fasta
2012_02_10_VIF_F1.raw Raw
2012_02_10_VIF_F2.raw Raw
2012_02_10_VIF_F3.raw Raw
2012_02_10_VIF_F4.raw Raw
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Publications


Although genetically compact, HIV-1 commandeers vast arrays of cellular machinery to sustain and protect it during cycles of viral outgrowth. Transposon-mediated saturation linker scanning mutagenesis was used to isolate fully replication-competent viruses harbouring a potent foreign epitope tag. Using these viral isolates, we performed differential isotopic labelling and affinity-capture mass spectrometric analyses on samples obtained from cultures of human lymphocytes to classify the vicinal i  ...[more]

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