title: Global landscape of HIV-human protein complexes.
abstract: Human immunodeficiency virus (HIV) has a small genome and therefore relies heavily on the host cellular machinery to replicate. Identifying which host proteins and complexes come into physical contact with the viral proteins is crucial for a comprehensive understanding of how HIV rewires the host's cellular machinery during the course of infection. Here we report the use of affinity tagging and purification mass spectrometry to determine systematically the physical interactions of all 18 HIV-1 proteins and polyproteins with host proteins in two different human cell lines (HEK293 and Jurkat). Using a quantitative scoring system that we call MiST, we identified with high confidence 497 HIV-human protein-protein interactions involving 435 individual human proteins, with ∼40% of the interactions being identified in both cell types. We found that the host proteins hijacked by HIV, especially those found interacting in both cell types, are highly conserved across primates. We uncovered a number of host complexes targeted by viral proteins, including the finding that HIV protease cleaves eIF3d, a subunit of eukaryotic translation initiation factor 3. This host protein is one of eleven identified in this analysis that act to inhibit HIV replication. This data set facilitates a more comprehensive and detailed understanding of how the host machinery is manipulated during the course of HIV infection.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158, USA.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Jäger
authors.forename: Peter
authors.initials: P
authors.lastname: Cimermancic
authors.forename: Natali
authors.initials: N
authors.lastname: Gulbahce
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Johnson
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: McGovern
authors.forename: Starlynn C
authors.initials: SC
authors.lastname: Clarke
authors.forename: Michael
authors.initials: M
authors.lastname: Shales
authors.forename: Gaelle
authors.initials: G
authors.lastname: Mercenne
authors.forename: Lars
authors.initials: L
authors.lastname: Pache
authors.forename: Kathy
authors.initials: K
authors.lastname: Li
authors.forename: Hilda
authors.initials: H
authors.lastname: Hernandez
authors.forename: Gwendolyn M
authors.initials: GM
authors.lastname: Jang
authors.forename: Shoshannah L
authors.initials: SL
authors.lastname: Roth
authors.forename: Eyal
authors.initials: E
authors.lastname: Akiva
authors.forename: John
authors.initials: J
authors.lastname: Marlett
authors.forename: Melanie
authors.initials: M
authors.lastname: Stephens
authors.forename: Iván
authors.initials: I
authors.lastname: D'Orso
authors.forename: Jason
authors.initials: J
authors.lastname: Fernandes
authors.forename: Marie
authors.initials: M
authors.lastname: Fahey
authors.forename: Cathal
authors.initials: C
authors.lastname: Mahon
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: O'Donoghue
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Todorovic
authors.forename: John H
authors.initials: JH
authors.lastname: Morris
authors.forename: David A
authors.initials: DA
authors.lastname: Maltby
authors.forename: Tom
authors.initials: T
authors.lastname: Alber
authors.forename: Gerard
authors.initials: G
authors.lastname: Cagney
authors.forename: Frederic D
authors.initials: FD
authors.lastname: Bushman
authors.forename: John A
authors.initials: JA
authors.lastname: Young
authors.forename: Sumit K
authors.initials: SK
authors.lastname: Chanda
authors.forename: Wesley I
authors.initials: WI
authors.lastname: Sundquist
authors.forename: Tanja
authors.initials: T
authors.lastname: Kortemme
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Hernandez
authors.forename: Charles S
authors.initials: CS
authors.lastname: Craik
authors.forename: Alma
authors.initials: A
authors.lastname: Burlingame
authors.forename: Andrej
authors.initials: A
authors.lastname: Sali
authors.forename: Alan D
authors.initials: AD
authors.lastname: Frankel
authors.forename: Nevan J
authors.initials: NJ
authors.lastname: Krogan
mesh_terms: D000345:Affinity Labels; D000595:Amino Acid Sequence; D017124:Conserved Sequence; D039621:Eukaryotic Initiation Factor-3 / Q000737:chemistry / Q000378:metabolism; D057809:HEK293 Cells; D015658:HIV Infections / Q000378:metabolism / Q000821:virology; D016333:HIV Protease / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D054884:Host-Pathogen Interactions; D054298:Human Immunodeficiency Virus Proteins / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D019169:Jurkat Cells; D013058:Mass Spectrometry; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D060066:Protein Interaction Maps / Q000502:physiology*; D015203:Reproducibility of Results; D014779:Virus Replication
chemical_list: D000345:Affinity Labels; C000609002:EIF3D protein, human; D039621:Eukaryotic Initiation Factor-3; D054298:Human Immunodeficiency Virus Proteins; D016333:HIV Protease