Host Cell Factors in HIV Replication: Meta-analysis of Genome-wide Studies

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2009 May 30

PMID 19478882

Citations 268

Authors

Frederic D Bushman

Nirav Malani

Jason Fernandes

Ivan DOrso

Gerard Cagney

Tracy L Diamond

Honglin Zhou

Daria J Hazuda

Amy S Espeseth

Renate Konig

Sourav Bandyopadhyay

Trey Ideker

Stephen P Goff

Nevan J Krogan

Alan D Frankel

John A T Young

Sumit K Chanda

Affiliations

Soon will be listed here.

Abstract

We have analyzed host cell genes linked to HIV replication that were identified in nine genome-wide studies, including three independent siRNA screens. Overlaps among the siRNA screens were very modest (<7% for any pairwise combination), and similarly, only modest overlaps were seen in pairwise comparisons with other types of genome-wide studies. Combining all genes from the genome-wide studies together with genes reported in the literature to affect HIV yields 2,410 protein-coding genes, or fully 9.5% of all human genes (though of course some of these are false positive calls). Here we report an "encyclopedia" of all overlaps between studies (available at http://www.hostpathogen.org), which yielded a more extensively corroborated set of host factors assisting HIV replication. We used these genes to calculate refined networks that specify cellular subsystems recruited by HIV to assist in replication, and present additional analysis specifying host cell genes that are attractive as potential therapeutic targets.

Citing Articles

Genome-wide siRNA library screening identifies human host factors that influence the replication of the highly pathogenic H5N1 influenza virus.

Wang G, Jiang L, Wang J, Li Q, Zhang J, Kong F mLife. 2025; 4(1):55-69.

PMID: 40026577 PMC: 11868839. DOI: 10.1002/mlf2.12168.

SIV infection and ARV treatment reshape the transcriptional and epigenetic profile of naïve and memory T cells .

Rahmberg A, Markowitz T, Mudd J, Ortiz A, Brenchley J J Virol. 2024; 98(6):e0028324.

PMID: 38780248 PMC: 11237756. DOI: 10.1128/jvi.00283-24.

CRISPR-Cas9 screen of E3 ubiquitin ligases identifies TRAF2 and UHRF1 as regulators of HIV latency in primary human T cells.

Rathore U, Haas P, Kumar V, Hiatt J, Haas K, Bouhaddou M mBio. 2024; 15(4):e0222223.

PMID: 38411080 PMC: 11005436. DOI: 10.1128/mbio.02222-23.

Comparison of the Biological Basis for Non-HIV Transmission to HIV-Exposed Seronegative Individuals, Disease Non-Progression in HIV Long-Term Non-Progressors and Elite Controllers.

Hokello J, Tyagi P, Dimri S, Sharma A, Tyagi M Viruses. 2023; 15(6).

PMID: 37376660 PMC: 10301403. DOI: 10.3390/v15061362.

Specialized DNA Structures Act as Genomic Beacons for Integration by Evolutionarily Diverse Retroviruses.

Kohio H, Ajoge H, Coleman M, Ndashimye E, Gibson R, Arts E Viruses. 2023; 15(2).

PMID: 36851678 PMC: 9962126. DOI: 10.3390/v15020465.

References

Mohan M, Aye P, Borda J, Alvarez X, Lackner A . Gastrointestinal disease in simian immunodeficiency virus-infected rhesus macaques is characterized by proinflammatory dysregulation of the interleukin-6-Janus kinase/signal transducer and activator of transcription3 pathway. Am J Pathol. 2007; 171(6):1952-65. PMC: 2111118. DOI: 10.2353/ajpath.2007.070017. View

Neville M, Stutz F, Lee L, Davis L, Rosbash M . The importin-beta family member Crm1p bridges the interaction between Rev and the nuclear pore complex during nuclear export. Curr Biol. 1997; 7(10):767-75. DOI: 10.1016/s0960-9822(06)00335-6. View

Schwartz O, Marechal V, Friguet B, Heard J . Antiviral activity of the proteasome on incoming human immunodeficiency virus type 1. J Virol. 1998; 72(5):3845-50. PMC: 109608. DOI: 10.1128/JVI.72.5.3845-3850.1998. View

Ciuffi A, Diamond T, Hwang Y, Marshall H, Bushman F . Modulating target site selection during human immunodeficiency virus DNA integration in vitro with an engineered tethering factor. Hum Gene Ther. 2006; 17(9):960-7. DOI: 10.1089/hum.2006.17.960. View

Goff S . Knockdown screens to knockout HIV-1. Cell. 2008; 135(3):417-20. PMC: 3598618. DOI: 10.1016/j.cell.2008.10.007. View

Earl P, Moss B, Doms R . Folding, interaction with GRP78-BiP, assembly, and transport of the human immunodeficiency virus type 1 envelope protein. J Virol. 1991; 65(4):2047-55. PMC: 240054. DOI: 10.1128/JVI.65.4.2047-2055.1991. View

Christ F, Thys W, De Rijck J, Gijsbers R, Albanese A, Arosio D . Transportin-SR2 imports HIV into the nucleus. Curr Biol. 2008; 18(16):1192-202. DOI: 10.1016/j.cub.2008.07.079. View

Mitchell R, Beitzel B, Schroder A, Shinn P, Chen H, Berry C . Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences. PLoS Biol. 2004; 2(8):E234. PMC: 509299. DOI: 10.1371/journal.pbio.0020234. View

Rines D, Tu B, Miraglia L, Welch G, Zhang J, Hull M . High-content screening of functional genomic libraries. Methods Enzymol. 2006; 414:530-65. DOI: 10.1016/S0076-6879(06)14028-8. View

10.

Kuras L, Borggrefe T, Kornberg R . Association of the Mediator complex with enhancers of active genes. Proc Natl Acad Sci U S A. 2003; 100(24):13887-91. PMC: 283516. DOI: 10.1073/pnas.2036346100. View

11.

Llano M, Vanegas M, Fregoso O, Saenz D, Chung S, Peretz M . LEDGF/p75 determines cellular trafficking of diverse lentiviral but not murine oncoretroviral integrase proteins and is a component of functional lentiviral preintegration complexes. J Virol. 2004; 78(17):9524-37. PMC: 506940. DOI: 10.1128/JVI.78.17.9524-9537.2004. View

12.

Studamire B, Goff S . Host proteins interacting with the Moloney murine leukemia virus integrase: multiple transcriptional regulators and chromatin binding factors. Retrovirology. 2008; 5:48. PMC: 2481268. DOI: 10.1186/1742-4690-5-48. View

13.

Gamble T, Vajdos F, Yoo S, Worthylake D, Houseweart M, Sundquist W . Crystal structure of human cyclophilin A bound to the amino-terminal domain of HIV-1 capsid. Cell. 1996; 87(7):1285-94. DOI: 10.1016/s0092-8674(00)81823-1. View

14.

Matthews P, Prendergast A, Leslie A, Crawford H, Payne R, Rousseau C . Central role of reverting mutations in HLA associations with human immunodeficiency virus set point. J Virol. 2008; 82(17):8548-59. PMC: 2519667. DOI: 10.1128/JVI.00580-08. View

15.

Konig R, Chiang C, Tu B, Yan S, DeJesus P, Romero A . A probability-based approach for the analysis of large-scale RNAi screens. Nat Methods. 2007; 4(10):847-9. DOI: 10.1038/nmeth1089. View

16.

Maertens G, Cherepanov P, Pluymers W, Busschots K, De Clercq E, Debyser Z . LEDGF/p75 is essential for nuclear and chromosomal targeting of HIV-1 integrase in human cells. J Biol Chem. 2003; 278(35):33528-39. DOI: 10.1074/jbc.M303594200. View

17.

Garrus J, von Schwedler U, Pornillos O, Morham S, Zavitz K, Wang H . Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding. Cell. 2001; 107(1):55-65. DOI: 10.1016/s0092-8674(01)00506-2. View

18.

Hutvagner G, Zamore P . RNAi: nature abhors a double-strand. Curr Opin Genet Dev. 2002; 12(2):225-32. DOI: 10.1016/s0959-437x(02)00290-3. View

19.

Li J, Tang H, Mullen T, Westberg C, Reddy T, Rose D . A role for RNA helicase A in post-transcriptional regulation of HIV type 1. Proc Natl Acad Sci U S A. 1999; 96(2):709-14. PMC: 15201. DOI: 10.1073/pnas.96.2.709. View

20.

Turlure F, Devroe E, Silver P, Engelman A . Human cell proteins and human immunodeficiency virus DNA integration. Front Biosci. 2004; 9:3187-208. DOI: 10.2741/1472. View