Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication.
Human Immunodeficiency Viruses (HIV-1 and HIV-2) rely upon host-encoded proteins to facilitate their replication. Here, we combined genome-wide siRNA analyses with interrogation of human interactome databases to assemble a host-pathogen biochemical network containing 213 confirmed host cellular factors and 11 HIV-1-encoded proteins. Protein complexes that regulate ubiquitin conjugation, proteolysis, DNA-damage response, and RNA splicing were identified as important modulators of early-stage HIV-1 infection. Additionally, over 40 new factors were shown to specifically influence the initiation and/or kinetics of HIV-1 DNA synthesis, including cytoskeletal regulatory proteins, modulators of posttranslational modification, and nucleic acid-binding proteins. Finally, 15 proteins with diverse functional roles, including nuclear transport, prostaglandin synthesis, ubiquitination, and transcription, were found to influence nuclear import or viral DNA integration. Taken together, the multiscale approach described here has uncovered multiprotein virus-host interactions that likely act in concert to facilitate the early steps of HIV-1 infection.
König
Renate
R
Infectious & Inflammatory Disease Center, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Zhou
Yingyao
Y
Elleder
Daniel
D
Diamond
Tracy L
TL
Bonamy
Ghislain M C
GM
Irelan
Jeffrey T
JT
Chiang
Chih-Yuan
CY
Tu
Buu P
BP
De Jesus
Paul D
PD
Lilley
Caroline E
CE
Seidel
Shannon
S
Opaluch
Amanda M
AM
Caldwell
Jeremy S
JS
Weitzman
Matthew D
MD
Kuhen
Kelli L
KL
Bandyopadhyay
Sourav
S
Ideker
Trey
T
Orth
Anthony P
AP
Miraglia
Loren J
LJ
Bushman
Frederic D
FD
Young
John A
JA
Chanda
Sumit K
SK
D002460:Cell Line; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D011506:Proteins / Q000378:metabolism*; D034622:RNA Interference; D020798:Two-Hybrid System Techniques; D014779:Virus Replication
D011506:Proteins