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.
Infectious & Inflammatory Disease Center, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Renate
R
König
Yingyao
Y
Zhou
Daniel
D
Elleder
Tracy L
TL
Diamond
Ghislain M C
GM
Bonamy
Jeffrey T
JT
Irelan
Chih-Yuan
CY
Chiang
Buu P
BP
Tu
Paul D
PD
De Jesus
Caroline E
CE
Lilley
Shannon
S
Seidel
Amanda M
AM
Opaluch
Jeremy S
JS
Caldwell
Matthew D
MD
Weitzman
Kelli L
KL
Kuhen
Sourav
S
Bandyopadhyay
Trey
T
Ideker
Anthony P
AP
Orth
Loren J
LJ
Miraglia
Frederic D
FD
Bushman
John A
JA
Young
Sumit K
SK
Chanda
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