Identification of host proteins required for HIV infection through a functional genomic screen
Abstract
HIV-1 exploits multiple host proteins during infection. We performed a large-scale small interfering RNA screen to identify host factors required by HIV-1 and identified more than 250 HIV-dependency factors (HDFs). These proteins participate in a broad array of cellular functions and implicate new pathways in the viral life cycle. Further analysis revealed previously unknown roles for retrograde Golgi transport proteins (Rab6 and Vps53) in viral entry, a karyopherin (TNPO3) in viral integration, and the Mediator complex (Med28) in viral transcription. Transcriptional analysis revealed that HDF genes were enriched for high expression in immune cells, suggesting that viruses evolve in host cells that optimally perform the functions required for their life cycle. This effort illustrates the power with which RNA interference and forward genetics can be used to expose the dependencies of human pathogens such as HIV, and in so doing identify potential targets for therapy.
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Host proteins with potential functions in the viral lifecycle have been identified using siRNA-based screens.
“Host proteins with potential functions in the viral lifecycle have also been identified using siRNA-based screens (125-127).”
From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [127]
GlyRS shows a mixed pattern of regulation upon HIV-1 infection.
“| Mixed pattern of regulation upon HIV-1 infection | GlyRS | 127 |”
From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [127]
The five ARSs EPRS, TyrRS, MetRS, HisRS, and PheRS exhibit a significant decrease (≥16-fold) in transcript levels.
“The five ARSs listed exhibit a significant decrease (Ն16-fold) in transcript levels.”
From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [127]
Transcript levels of EPRS, TyrRS, MetRS, HisRS, and PheRS decrease upon HIV-1 infection.
“| Levels of transcripts decrease upon HIV-1 infection b | EPRS a , TyrRS, MetRS a , HisRS, PheRS | 127 |”
From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [127]
Transcript levels of AsnRS and CysRS increase upon HIV-1 infection.
“| Levels of transcripts increase upon HIV-1 infection | AsnRS, CysRS | 127 |”
From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [127]
Five other ARSs, AlaRS, IleRS, LysRS, ValRS, and GlnRS, exhibit a moderate decrease (~4-fold) in transcript levels in HIV-1-infected cells.
“Five other ARSs, AlaRS, IleRS, LysRS, ValRS, and GlnRS, exhibit a moderate decrease (ϳ4fold) in HIV-1-infected cells.”
From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [127]
Cites
Host factors exploited by retroviruses
Goff, S. P. (2007) · Nature Reviews Microbiology · doi:10.1038/nrmicro1541 · Cited by 247 · see citing works
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Fernald, G., Capriotti, E., Daneshjou, R., Karczewski, K., & Altman, R. (2011) · Bioinform. · doi:10.1007/978-1-4020-6754-9_6751 · Cited by 6,249
Brass, A., Huang, I.-C., Benita, Y., John, S., Krishnan, M. N., Feeley, E., Ryan, B., Weyer, J., van der Weyden, L., Fikrig, E., et al. (2009) · Cell · doi:10.1016/j.cell.2009.12.017 · Cited by 1,292 · see citing works
“…S2), including a summary comparison of enriched GO categories for three whole-genome screens for host-factor modifiers of viral infection (HIV, [Brass et al., 2008], influenza A virus [this study], and WNV [Krishnan et al., 2008]), wherein each screen’s respective candidate gene list was…”
BackgroundMethodSelf-citationTRIM family proteins and their emerging roles in innate immunity
Ozato, K., Shin, D.-M., Chang, T.-H., & Morse, H. (2008) · Nature reviews. Immunology · doi:10.1038/nri2413 · Cited by 1,120 · see citing works
Global Analysis of Host-Pathogen Interactions that Regulate Early-Stage HIV-1 Replication
König, R., Zhou, Y., Elleder, D., Diamond, T. L., Bonamy, G. M. C., Irelan, J. T., Chiang, C.-Y., Tu, B. P., De Jesus, P. D., Lilley, C. E., et al. (2008) · Cell · doi:10.1016/j.cell.2008.07.032 · Cited by 960 · see citing works
“Our studies, combined with those of Brass et al. (2008), indicate the involvement of NUP153, RANBP2, and TNPO3 as factors involved in HIV-1 PIC import (Table 1).”
BackgroundMethodResultInfluentialAutophagy, Immunity, and Microbial Adaptations
Deretic, V. P., & Levine, B. (2009) · Cell Host & Microbe · doi:10.1016/j.chom.2009.05.016 · Cited by 868 · see citing works
“N IH -PA Author M anuscript N IH -PA Author M anuscript N IH -PA Author M anuscript Table 2 Microbial Adaptations to Evade or Use Autophagy to Promote Survival or Replication Microbe Adaptation Effects on hostpathogen interactions Microbial virulence factor/mechanism References VIRUSES RNA viruses Picornaviridae Polio…”
MethodInfluentialHuman Host Factors Required for Influenza Virus Replication
König, R., Stertz, S., Zhou, Y.-Y., Inoue, A., Hoffmann, H., Bhattacharyya, S., Alamares, J. G., Tscherne, D. M., Ortigoza, M., Liang, Y.-H., et al. (2010) · Nature · doi:10.1038/nature08699 · Cited by 866 · see citing works
“Genome-wide RNAi screens have enabled the identification of host factors required by a number of RNA viruses 5–7 8 9, 10 11, including an insect cell-based RNAi screen which implicated 110 Drosophila genes in influenza virus replication 12.”
Genome-scale RNAi screen for host factors required for HIV replication.
Zhou, H., Xu, M., Huang, Q., Gates, A. T., Zhang, X. D., Castle, J. C., Stec, E. M., Ferrer, M., Strulovici, B., Hazuda, D., et al. (2008) · Cell Host and Microbe · doi:10.1016/j.chom.2008.10.004 · Cited by 856 · see citing works
“(B) Effects of siRNA hits identified in this work and in Brass et al. (2008) on HIV replication.”
BackgroundMethodResultInfluentialLupberger, J., Zeisel, M., Xiao, F., Thumann, C., Fofana, I., Zona, L., Davis, C., Mee, C., Turek, M., Gorke, S., et al. (2011) · Nature Medicine · doi:10.1038/nm.2341 · Cited by 743 · see citing works
Global landscape of HIV–human protein complexes
Jäger, S., Cimermancic, P., Gulbahce, N., Johnson, J. R., McGovern, K. E., Clarke, S. C., Shales, M., Mercenne, G., Pache, L., Li, K., et al. (2012) · Nature · doi:10.1038/nature10719 · Cited by 731 · see citing works
Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication
Karlas, A., Machuy, N., Shin, Y.-J., Pleissner, K., Artarini, A., Heuer, D., Becker, D., Khalil, H., Ogilvie, L., Hess, S., et al. (2010) · Nature · doi:10.1038/nature08760 · Cited by 715 · see citing works
Prioritizing candidate disease genes by network-based boosting of genome-wide association dataPreprint
Lee, I., Singh-Blom, U. M., Wang, P. I., Shim, J. E., & Marcotte, E. M. (2011) · Genome Research · doi:10.1101/gr.118992.110 · Cited by 673 · see citing works
“down (Brass et al. 2008), were predictable by guilt-by-association in HumanNet.”
BackgroundInfluentialA Physical and Regulatory Map of Host-Influenza Interactions Reveals Pathways in H1N1 Infection
Shapira, S. D., Gat‐Viks, I., Shum, B. O. V., Dricot, A., DeGrace, M. M., Wu, L., Gupta, P. B., Hao, T., Silver, S. J., Root, D. E., et al. (2009) · Cell · doi:10.1016/j.cell.2009.12.018 · Cited by 630 · see citing works
“Previous studies on viral and host factors have focused on specific interactions but have not produced global models of the viral-host relationship, with few exceptions (Brass et al., 2008; Bushman et al., 2009; König et al., 2008; Krishnan et al., 2008; Li et al., 2009).”
BackgroundMunger, J. C., Bennett, B. D., Parikh, A., Feng, X., McArdle, J., RABITZ, H. A., Shenk, T. E., & Rabinowitz, J. D. (2008) · Nature Biotechnology · doi:10.1038/nbt.1500 · Cited by 630 · see citing works
HIV-1 accessory proteins--ensuring viral survival in a hostile environment.
Malim, M., & Emerman, M. (2008) · Cell Host and Microbe · doi:10.1016/j.chom.2008.04.008 · Cited by 628 · see citing works
“Interestingly, DCAF1 was also identified as an HIV-1-dependency factor (i.e., a protein whose expression promotes replication) in a large-scale siRNA screen using a viral strain that was deficient for Vpr (Brass et al., 2008).”
BackgroundInfluentialAvoiding the void: Cell-to-cell spread of human viruses
Sattentau, Q. (2008) · Nature Reviews Microbiology · doi:10.1038/nrmicro1972 · Cited by 614 · see citing works
Immunity and immunopathology to viruses: what decides the outcome?
Rouse, B. T., & Sehrawat, S. (2010) · Nature reviews. Immunology · doi:10.1038/nri2802 · Cited by 621 · see citing works
Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection
Goujon, C., Moncorgé, O., Bauby, H., Doyle, T., Ward, C. C., Schaller, T., Hué, S., Barclay, W., Schulz, R., & Malim, M. H. (2013) · Nature · doi:10.1038/nature12542 · Cited by 587 · see citing works
Heaton, N. S., Perera, R., Berger, K. L., Khadka, S., LaCount, D. J., Kuhn, R. J., & Randall, G. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010811107 · Cited by 566 · see citing works
RNA interference screen for human genes associated with West Nile virus infection
Krishnan, M. N., Ng, A., Sukumaran, B., Gilfoy, F. D., Uchil, P., Sultana, H., Brass, A., Adametz, R., Tsui, M., Qian, F., et al. (2008) · Nature · doi:10.1038/nature07207 · Cited by 542 · see citing works
Self-citationTranscription regulation by the Mediator complex
Soutourina, J. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.115 · Cited by 591 · see citing works
Rules of engagement: molecular insights from host–virus arms races
Daugherty, M. D., & Malik, H. S. (2012) · Annual Review of Genetics · doi:10.1146/annurev-genet-110711-155522 · Cited by 515 · see citing works
Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages
Kyei, G. B., Dinkins, C., Davis, A. S., Roberts, E., Singh, S. B., Dong, C., Wu, L., Kominami, E., Ueno, T., Yamamoto, A., et al. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200903070 · Cited by 509 · see citing works
“terestingly, a recent large scale siRNA screen of host cell factors required for human immunodeficiency virus (HIV) type 1 (HIV-1) replication has identified several Atg factors among >250 HIV dependency host genes (Brass et al., 2008).”
InfluentialHaploid Genetic Screens in Human Cells Identify Host Factors Used by Pathogens
Carette, J., Guimarães, C. P., Varadarajan, M., Park, A. S., Wuethrich, I., Godarova, A., Kotecki, M., Cochran, B., Spooner, E., Ploegh, H., et al. (2009) · Science · doi:10.1126/science.1178955 · Cited by 508 · see citing works
Flexible Use of Nuclear Import Pathways by HIV-1
Lee, K., Ambrose, Z., Martin, T. D., Oztop, I., Mulky, A., Julias, J. G., Vandegraaff, N., Baumann, J. G., Wang, R., Yuen, W., et al. (2010) · Cell Host and Microbe · doi:10.1016/j.chom.2010.02.007 · Cited by 472 · see citing works
“Genome-wide screens using RNA interference (RNAi) technologies have revealed a wealth of host factors that, when depleted from cells, can limit HIV-1 infection (Brass et al., 2008; König et al., 2008; Zhou et al., 2008).”
BackgroundResultSelf-citationSchaller, T., Ocwieja, K. E., Rasaiyaah, J., Price, A. J., Brady, T. L., Roth, S. L., Hué, S., Fletcher, A. J., Lee, K., KewalRamani, V. N., et al. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002439 · Cited by 470 · see citing works
Host Cell Factors in HIV Replication: Meta-Analysis of Genome-Wide Studies
Bushman, F. D., Malani, N., Fernandes, J. D., D’Orso, I., Cagney, G., Diamond, T. L., Zhou, H., Hazuda, D. J., Espeseth, A. S., König, R., et al. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000437 · Cited by 452 · see citing works
“, but each method is imperfect, so that correct calls will be mixed with false positives, and authentic functions will be missed at some frequency, yielding false negatives. For example, three small interfering RNA (siRNA) screens have been reported that interrogated most of the human genes for effects on HIV infection”
BackgroundA Functional Genomic Screen Identifies Cellular Cofactors of Hepatitis C Virus Replication
Tai, A. W., Benita, Y., Peng, L. F., Kim, S.-S., Sakamoto, N., Xavier, R. J., & Chung, R. T. (2009) · Cell Host & Microbe · doi:10.1016/j.chom.2009.02.001 · Cited by 423 · see citing works
“Similarly, relatively little overlap has been observed among the hits in three genome-wide RNAi screens for HIV host cofactors (Brass et al., 2008; König et al., 2008; Zhou et al., 2008).”
BackgroundMethodInfluentialSelf-citationHIV-1 capsid: the multifaceted key player in HIV-1 infection
Campbell, E. M., & Hope, T. J. (2015) · Nature Reviews Microbiology · doi:10.1038/nrmicro3503 · Cited by 430 · see citing works
Double-Stranded RNA Sensors and Modulators in Innate Immunity
Hur, S. (2019) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042718-041356 · Cited by 420 · see citing works
Yan, N., Regalado-Magdos, A. D., Stiggelbout, B., Lee‐Kirsch, M. A., & Lieberman, J. (2010) · Nature Immunology · doi:10.1038/ni.1941 · Cited by 522 · see citing works
Self-citationKudchodkar, S. B., & Levine, B. (2009) · Reviews in Medical Virology · doi:10.1002/rmv.630 · Cited by 278 · see citing works
“A possible role for autophagy or Atg genes in supporting HIV infection was suggested by the identification of Atg7, Atg8, Atg12 and Atg16L2 in an siRNA screen in HeLa cells for genes important in HIV replication; however, it remains to be determined if these genes function in HIV infection in natural HIV target cells…”
BackgroundNuclear import by Karyopherin-βs: recognition and inhibition
Chook, Y., & Süel, K. E. (2010) · Biochimica et Biophysica Acta · doi:10.1016/j.bbamcr.2010.10.014 · Cited by 402 · see citing works
High content screening: seeing is believing
Zanella, F., Lorens, J. B., & Link, W. (2010) · Trends in biotechnology · doi:10.1016/j.tibtech.2010.02.005 · Cited by 391 · see citing works
A genome-wide genetic screen for host factors required for hepatitis C virus propagation
Li, Q.-S., Brass, A., Ng, A., Hu, Z.-Y., Xavier, R., Liang, T., & Elledge, S. (2009) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0907439106 · Cited by 391 · see citing works
“Our efforts to find HIV-dependency factors (HDFs) also found that OST48 was required for late-stage viral replication, consistent with its playing a role in glycosylation of the viral envelope spike (13).”
BackgroundSelf-citationTracing the retrograde route in protein trafficking.
Johannes, L., & Popoff, V. (2008) · Cell · doi:10.1016/j.cell.2008.12.009 · Cited by 385 · see citing works
“Strikingly, a recent functional genomics screen has uncovered requirements for several retrograde trafficking factors in HIV infection (Brass et al., 2008).”
Membrane nanotubes: dynamic long-distance connections between animal cells
Davis, D., & Sowinski, S. (2008) · Nature reviews. Molecular cell biology · doi:10.1038/nrm2399 · Cited by 371 · see citing works
The Mediator complex and transcription regulation
Poss, Z. C., Ebmeier, C. C., & Taatjes, D. J. (2013) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2013.840259 · Cited by 364 · see citing works
“MED7 was shown to be important for early HIV reverse transcription (Konig et al., 2008) and MED4, MED6, MED7, MED14 and MED28 were required for HIV infection (Brass et al., 2008).”
BackgroundDuan, F., Duitama, J., Seesi, S. A., Ayres, C. M., Corcelli, S. A., Pawashe, A., Blanchard, T., McMahon, D., Sidney, J., Sette, A., et al. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20141308 · Cited by 378 · see citing works
NEAT1 Long Noncoding RNA and Paraspeckle Bodies Modulate HIV-1 Posttranscriptional Expression
Zhang, Q., Chen, C., Yedavalli, V. S. R. K., & Jeang, K. (2013) · mBio · doi:10.1128/mbio.00596-12 · Cited by 390 · see citing works
Cellular networks involved in the influenza virus life cycle
Watanabe, T., Watanabe, S., & Kawaoka, Y. (2010) · Cell Host and Microbe · doi:10.1016/j.chom.2010.05.008 · Cited by 355 · see citing works
“Now, this technology offers a new exciting tool for the exploration of novel host genes involved in virus replication (Brass et al., 2008, 2009; Cherry et al., 2005; Goff, 2008; Hao et al., 2008; König et al., 2008, 2010; Krishnan et al., 2008; Li et al., 2009; Zhou et al., 2008).”
BackgroundRNA Interference: From Basic Research to Therapeutic Applications
Kurreck, J. (2009) · Angewandte Chemie International Edition · doi:10.1002/anie.200802092 · Cited by 332 · see citing works
Craigie, R., & Bushman, F. D. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006890 · Cited by 327 · see citing works
“…have been performed to identify genes that when reduced in dosage using small interfering RNA (siRNA), diminish HIV infection, and several of the identified host factors have been mapped to the integration part of the viral replication cycle (Brass et al. 2008; Konig et al. 2008; Zhou et al. 2008).”
BackgroundThe spread, treatment, and prevention of HIV-1: evolution of a global pandemic
Cohen, M. S., Hellmann, N., Levy, J. A., DeCock, K. M., & Lange, J. M. A. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34706 · Cited by 301 · see citing works
“Most recently, Brass et al. (28) applied a unique approach, using siRNA to identify “HIV dependency factors.””
A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors
Park, R. J.-H., Wang, T., Koundakjian, D., Hultquist, J. F., Lamothe, P. A., Monel, B., Schumann, K., Yu, H., Krupzcak, K. M., García-Beltrán, W. F., et al. (2016) · Nature Genetics · doi:10.1038/ng.3741 · Cited by 329 · see citing works
Nuclear architecture dictates HIV-1 integration site selection
Marini, B., Kertész‐Farkas, A., Ali, H., Lucic, B., Lisek, K., Manganaro, L., Pongor, S., Luzzati, R., Recchia, A., Mavilio, F., et al. (2015) · Nature · doi:10.1038/nature14226 · Cited by 336 · see citing works
Adenosine Deaminases Acting on RNA (ADARs) are both Antiviral and Proviral Dependent upon the Virus
Samuel, C. (2011) · Virology · doi:10.1016/j.virol.2010.12.004 · Cited by 319 · see citing works
“Several host cell machineries and factors are utilized during HIV-1 replication including those for viral RNA transcription and processing (Brass et al., 2008; Bushman et al., 2009; Knipe et al., 2007).”
BackgroundPathogenesis of flavivirus infections: using and abusing the host cell.
Fernandez-Garcia, M., Mazzon, M., Jacobs, M., & Amara, A. (2009) · Cell Host and Microbe · doi:10.1016/j.chom.2009.04.001 · Cited by 319 · see citing works
“Recent experience of three RNAi screens of human genes involved in human immunodeficiency virus (HIV) infection revealed that only a few genes were identified consistently across three independently conducted screens (Brass et al., 2008; Konig et al., 2008; Zhou et al., 2008), highlighting the danger of overinterpreti…”
BackgroundStrategies to inhibit entry of HBV and HDV into hepatocytes.
Urban, S., Bartenschlager, R., Kubitz, R., & Zoulim, F. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.04.030 · Cited by 315 · see citing works
Price, A. J., Jacques, D. A., McEwan, W. A., Fletcher, A. J., Essig, S., Chin, J. W., Halambage, U. D., Aiken, C., & James, L. C. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1004459 · Cited by 284 · see citing works
Genomic Screening with RNAi: Results and Challenges
Mohr, S. E., Bakal, C., & Perrimon, N. (2010) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060408-092949 · Cited by 281 · see citing works
Cone-shaped HIV-1 capsids are transported through intact nuclear poresPreprint
Zila, V., Margiotta, E., Turoňová, B., Müller, T. G., Zimmerli, C., Mattei, S., Allegretti, M., Börner, K., Rada, J., Müller, B., et al. (2020) · bioRxiv · doi:10.1101/2020.07.30.193524 · Cited by 300 · see citing works
“Several nucleoporins (NUPs), most notably the FG-repeat containing NUP358 and NUP153 were also reported to facilitate nuclear entry of HIV-1 (Brass et al., 2008; Di Nunzio et al., 2012; König et al., 2008).”
BackgroundZhou, J.-H., Swiderski, P., Li, H.-T., Zhang, J., Neff, C., Akkina, R., & Rossi, J. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp185 · Cited by 284 · see citing works
“It has been demonstrated that more than 250 HIV-dependency factors (HDFs) are required by HIV infection ( 48 ).”
BackgroundA single-molecule view of transcription reveals convoys of RNA polymerases and multi-scale bursting
Tantale, K., Mueller, F., Kozulic-Pirher, A., Lesne, A., Victor, J., Robert, M.-C., Capozi, S., Chouaib, R., Baecker, V., Langerak, J. M., et al. (2016) · Nature Communications · doi:10.1038/ncomms12248 · Cited by 286 · see citing works
Campbell, G. R., & Spector, S. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002689 · Cited by 282 · see citing works
“[28,31,39], the supernatant p24 antigen concentration in Beclin-1 silenced cells was decreased in the absence of 1,25D3 regardless of M.”
BackgroundMatreyek, K. A., Yücel, S. S., Li, X., & Engelman, A. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003693 · Cited by 280 · see citing works
“…been shown to participate in HIV-1 nuclear import, with perhaps the most promising candidates emerging from a series of genome-wide RNA interference (RNAi) screens; factors identified in more than one of these screens include transportin-3 (TNPO3 or TRN-SR2), NUP358 (RANBP2), and NUP153 [15–17].”
BackgroundSelf-citationAPOBEC proteins and intrinsic resistance to HIV-1 infection
Malim, M. H. (2008) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2008.0185 · Cited by 276 · see citing works
Viral immune modulators perturb the human molecular network by common and unique strategies
Pichlmair, A., Kandasamy, K., Alvisi, G., Mulhern, O., Sacco, R., Habjan, M., Binder, M., Stefanovic, A., Eberle, C.-A., Goncalves, A., et al. (2012) · Nature · doi:10.1038/nature11289 · Cited by 262 · see citing works
CPSF6 Defines a Conserved Capsid Interface that Modulates HIV-1 Replication
Price, A., Fletcher, A. J., Schaller, T., Elliott, T., Lee, K., KewalRamani, V., Chin, J., Towers, G., & James, L. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002896 · Cited by 276 · see citing works
Yeung, M. L., Houzet, L., Yedavalli, V. S. R. K., & Jeang, K. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.010033 · Cited by 263 · see citing works
Blanchet, F. P., Moris, A., Nikolic, D. S., Lehmann, M., Cardinaud, S., Stalder, R., Garcia, E., Dinkins, C., Leuba, F., Wu, L., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.04.011 · Cited by 273 · see citing works
“, 2008; Zhou and Spector, 2008), although autophagy has been implicated in resulting in higher viral yields in other cell types (Brass et al., 2008; Kyei et al., 2009).”
BackgroundLimou, S., Clerc, S. L., Coulonges, C., Carpentier, W., Dina, C., Delaneau, O., Labib, T., Taing, L., Sladek, R., Deveau, C., et al. (2009) · Journal of Infectious Diseases · doi:10.1086/596067 · Cited by 270 · see citing works
“and replication [32], suggesting that this RNA polymerase I sub-”
BackgroundAutophagy is involved in influenza A virus replication
Zhou, Z., Jiang, X.-J., Liu, D., Fan, Z., Hu, X., Yan, J., Wang, M., & Gao, G. (2009) · Autophagy · doi:10.4161/auto.5.3.7406 · Cited by 269 · see citing works
Darcis, G., Kula, A., Bouchat, S., Fujinaga, K., Corazza, F., Ait-Ammar, A., Delacourt, N., Mélard, A., Kabeya, K., Vanhulle, C., et al. (2015) · PLoS Pathogens · doi:10.1371/journal.ppat.1005063 · Cited by 268
Human immunodeficiency virus type 1, human protein interaction database at NCBI
Fu, W., Sanders-Beer, B. E., Katz, K., Maglott, D. R., Pruitt, K. D., & Ptak, R. G. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn708 · Cited by 245 · see citing works
Vinayagam, A., Gibson, T. E., Lee, H., Yilmazel, B., Roesel, C. L., Hu, Y., Kwon, Y. V., Sharma, A., Liu, Y., Perrimon, N., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1603992113 · Cited by 249 · see citing works
RNA-binding proteins in Mendelian disease
Castelló, A., Fischer, B., Hentze, M. W., & Preiß, T. (2013) · Trends in Genetics · doi:10.1016/j.tig.2013.01.004 · Cited by 255 · see citing works
Regulation of WASH-Dependent Actin Polymerization and Protein Trafficking by Ubiquitination
Hao, Y.-H., Doyle, J., Ramanathan, S., Gomez, T. S., Jia, D., Xu, M., Chen, Z. J., Billadeau, D. D., Rosen, M. K., & Potts, P. R. (2013) · Cell · doi:10.1016/j.cell.2013.01.051 · Cited by 238 · see citing works
“Endosome-to-Golgi transport is essential for cellular entry of pathogenic toxins, such as Shiga, cholera, and ricin, as well as viral pathogens such as HIV (Brass et al., 2008; Sandvig and van Deurs, 2005).”
Reactivation of Latent HIV-1 by Inhibition of BRD4
Zhu, J. K., Gaiha, G. D., John, S. P., Pertel, T., Chin, C. R., Gao, G., Qu, H., Walker, B. D., Elledge, S. J., & Brass, A. L. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.09.008 · Cited by 246 · see citing works
“Our work also demonstrates that in addition to HDFs that are needed by HIV-1 (Brass et al., 2008) and HIV-1 restriction factors (HRFs) that have evolved to specifically inhibit the virus (Yan and Chen, 2012), there exists a third functional class of host factors, HIV-1 competitive factors (HCFs);…”
BackgroundMethodSelf-citationHuang, Q., Chan, K. Y., Tobey, I. G., Chan, Y. A., Poterba, T., Boutros, C. L., Balazs, A. B., Daneman, R., Bloom, J. M., Seed, C., et al. (2019) · PLOS ONE · doi:10.1371/journal.pone.0225206 · Cited by 234 · see citing works
“The Ly6 gene family also influences susceptibility to infection by HIV126,27, Flaviviridae (yellow fever virus, dengue, and West Nile virus28, Influenza A29, and Marek’s disease virus in chickens30.”
BackgroundWheeler, L. A., Trifonova, R. T., Vrbanac, V. D., Basar, E., McKernan, S., Xu, Z., Seung, E., Déruaz, M., Dudek, T., Einarsson, J. I., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45876 · Cited by 227 · see citing works
Self-citationEating the enemy within: autophagy in infectious diseases
Orvedahl, A., & Levine, B. (2008) · Cell Death and Differentiation · doi:10.1038/cdd.2008.130 · Cited by 232 · see citing works
“68 As noted above, autophagy also mediates cell death of bystander T cells in HIV infection through CXCR4 binding to HIV envelope proteins.”
BackgroundMatreyek, K. A., & Engelman, A. (2011) · Journal of Virology · doi:10.1128/jvi.00325-11 · Cited by 224 · see citing works
“In addition to TNPO3, two major constituent proteins of the NPC, nucleoporins NUP358/RanBP2 and NUP153, were identified in two of the siRNA screens (7, 39).”
BackgroundSelf-citationA CRISPR-Based Screen Identifies Genes Essential for West-Nile-Virus-Induced Cell Death
Ma, H., Dang, Y., Wu, Y., Jia, G., Anaya, E., Zhang, J., Abraham, S., Choi, J.-G., Shi, G., Qi, L., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.06.049 · Cited by 217 · see citing works
“For example, the overlap was poor between three independent genome-wide functional screens using siRNA performed to identify host genes linked to HIV replication (Brass et al., 2008; Konig et al., 2008; Zhou et al., 2008).”
BackgroundDrug Target Prediction and Repositioning Using an Integrated Network-Based Approach
Emig, D., Ivliev, A. E., Pustovalova, O., Lancashire, L., Bureeva, S. V., Nikolsky, Y., & Bessarabova, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060618 · Cited by 242 · see citing works
The IFITMs Inhibit Zika Virus Replication
Savidis, G., Perreira, J. M., Portmann, J. M., Meraner, P., Guo, Z., Green, S., & Brass, A. L. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.05.074 · Cited by 226 · see citing works
“…The IFITMs have been shown to restrict viral replication by blocking fusion-pore formation and the entry of the viral genome and its associated proteins into the cytosol (Bailey et al., 2014; Brass et al., 2008; Feeley et al., 2011; Li et al., 2013; Lin et al., 2013; Perreira et al., 2013).”
BackgroundSelf-citationHost-Directed Antiviral Therapy
Kumar, N., Sharma, S., Kumar, R., Tripathi, B. N., Barua, S., Ly, H., & Rouse, B. T. (2020) · Clinical Microbiology Reviews · doi:10.1128/cmr.00168-19 · Cited by 281 · see citing works
The APOBEC3 Family of Retroelement Restriction Factors
Refsland, E. W., & Harris, R. S. (2013) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-37765-5_1 · Cited by 209 · see citing works
Systems Biology in Immunology: A Computational Modeling Perspective
Germain, R. N., Meier‐Schellersheim, M., Nita‐Lazar, A., & Fraser, I. D. C. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101317 · Cited by 203 · see citing works
MicroRNA profile changes in human immunodeficiency virus type 1 (HIV-1) seropositive individuals
Houzet, L., Yeung, M.-L., de Lame, V., Desai, D., Smith, S. M., & Jeang, K. (2008) · Retrovirology · doi:10.1186/1742-4690-5-118 · Cited by 214
“The course of human immunodeficiency virus (HIV-1) infection in cells is impacted by the action of several hundred host proteins [12-16].”
BackgroundDalmasso, C., Carpentier, W., Meyer, L., Rouzioux, C., Goujard, C., Chaix, M., Lambotte, O., Avettand-Fenoel, V., Clerc, S. L., de Senneville, L. D., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003907 · Cited by 213 · see citing works
“…plasma HIV-RNA is a composite marker reflecting viral fitness, replicative capacity and host control, while intracellular HIV-DNA levels reflect the establishment of HIV reservoirs and, thereof, the effect of numerous host proteins that may interact with the intracellular viral lifecycle [10].”
BackgroundHIV Integration Targeting: A Pathway Involving Transportin-3 and the Nuclear Pore Protein RanBP2
Ocwieja, K. E., Brady, T. L., Ronen, K., Huegel, A., Roth, S. L., Schaller, T., James, L. C., Towers, G. J., Young, J. A. T., Chanda, S. K., et al. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1001313 · Cited by 212 · see citing works
“Passage through the pore is likely a preferred route of nuclear entry for HIV-1 even in dividing cells – several components of the nuclear pore are required for efficient infection of dividing cells, even though PICs might access the nucleus during nuclear breakdown in mitosis”
BackgroundStrunze, S., Engelke, M., Wang, I.-H., Puntener, D., Boucke, K., Schleich, S., Way, M., Schoenenberger, P., Burckhardt, C. J., & Greber, U. (2011) · Cell Host and Microbe · doi:10.1016/j.chom.2011.08.010 · Cited by 209 · see citing works
Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection
Li, B., Clohisey, S., Chia, B. S., Wang, B., Cui, A., Eisenhaure, T., Schweitzer, L. D., Hoover, P., Parkinson, N., Nachshon, A., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-13965-x · Cited by 232 · see citing works
Abdulrahman, B., Khweek, A. A., Akhter, A., Caution, K. J., Kotrange, S., Abdelaziz, D., Newland, C., Rosales-Reyes, R., Kopp, B., McCoy, K., et al. (2011) · Autophagy · doi:10.4161/auto.7.11.17660 · Cited by 200 · see citing works
Arhel, N. (2010) · Retrovirology · doi:10.1186/1742-4690-7-96 · Cited by 200 · see citing works
Krishnan, L., Matreyek, K. A., Oztop, I., Lee, K., Tipper, C. H., Li, X., Dar, M., KewalRamani, V., & Engelman, A. (2009) · Journal of Virology · doi:10.1128/jvi.01899-09 · Cited by 196 · see citing works
“MLV, in contrast, efficiently infected TNPO3 knockdown cells (5, 13, 30), and recombinant TNPO3 and MLV IN proteins failed to interact under conditions where an HIV-1 IN-TNPO3 interaction was detected.”
BackgroundResultInfluentialSelf-citationHuman Nucleoporins Promote HIV-1 Docking at the Nuclear Pore, Nuclear Import and Integration
Nunzio, F. D., Danckaert, A., Fricke, T., Perez, P., Fernandez, J., Perret, E., Roux, P., Shorte, S., Charneau, P., Diaz-Griffero, F., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046037 · Cited by 195 · see citing works
HIV pathogenesis: 25 years of progress and persistent challenges
Levy, J. A. (2008) · AIDS · doi:10.1097/qad.0b013e3283217f9f · Cited by 177 · see citing works
Viruses and the autophagy machinery
Dreux, M., & Chisari, F. (2010) · Cell Cycle · doi:10.4161/cc.9.7.11109 · Cited by 190 · see citing works
John, S., Chin, C. R., Perreira, J. M., Feeley, E., Aker, A. M., Savidis, G., Smith, S. E., Elia, A., Everitt, A., Vora, M. M., et al. (2013) · Journal of Virology · doi:10.1128/jvi.00481-13 · Cited by 187 · see citing works
Self-citationRotger, M., Dang, K. K., Fellay, J., Heinzen, E., Feng, S., Descombes, P., Shianna, K., Ge, D., Günthard, H., Goldstein, D., et al. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000781 · Cited by 187 · see citing works
“) were all upregulated with increasing viral load, which is consistent with their general dependence on the interferon pathways. A number of chemokines and chemokine receptors were also positively modulated with increasing viremia. We also identified differentially expressed genes that are present in both the current…”
ResultTapping the RNA world for therapeutics
Lieberman, J. (2018) · Nature Structural & Molecular Biology · doi:10.1038/s41594-018-0054-4 · Cited by 195 · see citing works
Self-citationLi, Q.-S., Pène, V., Krishnamurthy, S. R., Cha, H., & Liang, T. (2013) · Nature Medicine · doi:10.1038/nm.3190 · Cited by 183 · see citing works
CD4+ T cells from elite controllers resist HIV-1 infection by selective upregulation of p21
Chen, H., Li, C., Huang, J., Cung, T. D. H., Seiss, K., Beamon, J., Carrington, M. N., Porter, L. C., Burke, P. S., Yang, Y., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44539 · Cited by 175 · see citing works
Self-citationHIV-1 Uncoating: Connection to Nuclear Entry and Regulation by Host Proteins
Ambrose, Z., & Aiken, C. (2014) · Virology · doi:10.1016/j.virol.2014.02.004 · Cited by 180 · see citing works
“Most notably, in 2008 three groups screened siRNA libraries to identify multiple proteins involved in early HIV-1 life cycle events (Brass et al., 2008; Konig et al., 2008; Zhou et al., 2008).”
InfluentialLentiviral delivery of short hairpin RNAs
Manjunath, N., Wu, H., Subramanya, S., & Shankar, P. (2009) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2009.03.004 · Cited by 165 · see citing works
“In fact, a recent genome-wide RNAi screen has identified several host genes necessary for viral replication [150].”
The Take and Give Between Retrotransposable Elements and their Hosts
Beauregard, A., Curcio, M. J., & Belfort, M. (2008) · Annual Review of Genetics · doi:10.1146/annurev.genet.42.110807.091549 · Cited by 168 · see citing works
A Physical Interaction Network of Dengue Virus and Human Proteins
Khadka, S., Vangeloff, A. D., Zhang, C., Siddavatam, P., Heaton, N. S., Wang, L., Sengupta, R., Sahasrabudhe, S., Randall, G., Gribskov, M., et al. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.012187 · Cited by 175 · see citing works
Nup153 and Nup98 bind the HIV-1 core and contribute to the early steps of HIV-1 replication
Nunzio, F. D., Fricke, T., Miccio, A., Valle-Casuso, J., Perez, P., Souque, P., Rizzi, E., Severgnini, M., Mavilio, F., Charneau, P., et al. (2013) · Retrovirology · doi:10.1186/1742-4690-10-s1-p111 · Cited by 171 · see citing works
“…(Ao et al., 2010), 3) importin α/ importin β heterodimer (Fassati et al., 2003; Gallay et al., 1997; Hearps and Jans, 2006), 4) transportin-SR2/TNPO3 (Brass et al., 2008; Christ et al., 2008; Konig et al., 2008; Krishnan et al., 2010; Levin et al., 2010; Thys et al., 2011; Valle-Casuso et al.,…”
BackgroundHultquist, J. F., Schumann, K., Woo, J. M., Manganaro, L., McGregor, M. J., Doudna, J., Simon, V., Krogan, N. J., & Marson, A. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.09.080 · Cited by 170 · see citing works
- Authors
- Brass, A. L., Dykxhoorn, D. M., Benita, Y., Yan, N., Engelman, A., Xavier, R. J., Lieberman, J., & Elledge, S. J.
- Affiliations
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- Science
- Published
- 2008-02-15
- Volume
- 319
- Issue
- 5865
- Pages
- 921-926
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2145848202
- Cited by
- 1,449
- References
- 0
- Citations by year
- 2026: 12 · 2025: 18 · 2024: 26 · 2023: 28 · 2022: 38 · 2021: 38 · 2020: 52 · 2019: 59 · 2018: 71 · 2017: 53 · 2016: 62 · 2015: 96 · 2014: 90 · 2013: 150 · 2012: 148
- FWCI
- 57.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Allergy and Infectious Diseases (U19AI056900, AI052014, AI 062773, R01AI062773, R01AI052014, P30AI060354)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK040561)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Keywords
- HIV-1, host factors, host-virus interaction, Rab6, viral entry, karyopherins, TNPO3, viral integration, Mediator complex, MED28, viral transcription, antiviral drug targets
- MeSH terms
- Cytoskeletal Proteins, Humans, Proteins, Transcription, Genetic, Virus Replication, HIV-1, HIV Infections, Virus Integration, Computational Biology, rab GTP-Binding Proteins, Genomics, Karyopherins, Vesicular Transport Proteins, RNA Interference, RNA, Small Interfering, Cell Line, Tumor, Intracellular Signaling Peptides and Proteins, Virus Internalization, Human Immunodeficiency Virus Proteins, Host-Pathogen Interactions, Mediator Complex
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