Genome-Scale RNAi Screen for Host Factors Required for HIV Replication

被引：614

作者：

Zhou, Honglin ^{[1
]}

Xu, Min ^{[1
]}

Huang, Qian ^{[1
]}

Gates, Adam T. ^{[1
]}

Zhang, Xiaohua D. ^{[2
]}

Castle, John C. ^{[3
]}

Stec, Erica ^{[4
]}

Ferrer, Marc ^{[4
]}

Strulovici, Berta ^{[4
]}

Hazuda, Daria J. ^{[1
]}

Espeseth, Amy S. ^{[1
]}

机构：

[1] Merck & Co Inc, Dept Virus & Cell Biol, West Point, PA 19486 USA

[2] Merck & Co Inc, Dept Biometr Res, West Point, PA 19486 USA

[3] Merck & Co Inc, Rosetta Inpharmat LLC, Seattle, WA 98109 USA

[4] Merck & Co Inc, Dept Automated Biotechnol, West Point, PA 19486 USA

来源：

CELL HOST & MICROBE | 2008年 / 4卷 / 05期

关键词：

D O I：

10.1016/j.chom.2008.10.004

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Human immunodeficiency virus (HIV)-1 depends on the host cell machinery to support its replication. To discover cellular factors associated with HIV-1 replication, we conducted a genome-scale siRNA screen, revealing more than 311 host factors, including 267 that were not previously linked to HIV. Surprisingly, there was little overlap between these genes and the HIV dependency factors described recently. However, an analysis of the genes identified in both screens revealed overlaps in several of the associated pathways or protein complexes, including the SP1/mediator complex and the NF-kappa B signaling pathway. cDNAs for a subset of the identified genes were used to rescue HIV replication following knockdown of the cellular mRNA providing strong evidence that the following six genes are previously uncharacterized host factors for HIV: AKT1, PRKAA1, CD97, NEIL3, BMP2K, and SERPINB6. This study highlights both the power and shortcomings of large scale loss-of-function screens in discovering host-pathogen interactions.

引用

页码：495 / 504

页数：10

共 35 条

[1] Molecular ordering in HIV-induced apoptosis - Oxidative stress, activation of caspases, and cell survival are regulated by transaldolase [J].

Banki, K ;

Hutter, E ;

Gonchoroff, NJ ;

Perl, A .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (19) :11944-11953

[2] The ovalbumin serpins revisited: Perspective from the chicken genome of clade B serpin evolution in vertebrates [J].

Benarafa, C ;

Remold-O'Donnell, E .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (32) :11367-11372

[3] Recruitment of cyclin T1/P-TEFb to an HIV type I long terminal repeat promoter proximal RNA target is both necessary and sufficient for full activation of transcription [J].

Bieniasz, PD ;

Grdina, TA ;

Bogerd, HP ;

Cullen, BR .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (14) :7791-7796

[4] The AMP-activated protein kinase prevents ceramide synthesis de novo and apoptosis in astrocytes [J].

Blázquez, C ;

Geelen, MJH ;

Velasco, G ;

Guzmán, M .

FEBS LETTERS, 2001, 489 (2-3) :149-153

[5] Extracellular HIV-1 Tat protein activates phosphatidylinositol 3- and Akt/PKB kinases in CD4(+) T lymphoblastoid Jurkat cells [J].

Borgatti, P ;

Zauli, G ;

Colamussi, ML ;

Gibellini, D ;

Previati, M ;

Cantley, LL ;

Capitani, S .

EUROPEAN JOURNAL OF IMMUNOLOGY, 1997, 27 (11) :2805-2811

[6]

Brass AL, 2008, SCIENCE, V319, P921, DOI 10.1126/science.1152725

[7] A quantitative assay for HIV DNA integration in vivo [J].

Butler, SL ;

Hansen, MST ;

Bushman, FD .

NATURE MEDICINE, 2001, 7 (05) :631-634

[8]

CASTLE JC, 2008, NAT GENET IN PRESS

[9] FUSION FROM WITHOUT DIRECTED BY HUMAN-IMMUNODEFICIENCY-VIRUS PARTICLES [J].

CLAVEL, F ;

CHARNEAU, P .

JOURNAL OF VIROLOGY, 1994, 68 (02) :1179-1185

[10]

Clavel F, 2004, NEW ENGL J MED, V350, P1023, DOI 10.1056/NEJM2ra025195

← 1 2 3 4 →