Defective HIV-1 proviruses produce viral proteins
Open accessAbstract
HIV-1 proviruses persist in the CD4 + T cells of HIV-infected individuals despite years of combination antiretroviral therapy (cART) with suppression of HIV-1 RNA levels <40 copies/mL. Greater than 95% of these proviruses detected in circulating peripheral blood mononuclear cells (PBMCs) are referred to as “defective” by virtue of having large internal deletions and lethal genetic mutations. As these defective proviruses are unable to encode intact and replication-competent viruses, they have long been thought of as biologically irrelevant “graveyard” of viruses with little significance to HIV-1 pathogenesis. Contrary to this notion, we have recently demonstrated that these defective proviruses are not silent, are capable of transcribing novel unspliced forms of HIV-RNA transcripts with competent open reading frames (ORFs), and can be found in the peripheral blood CD4 + T cells of patients at all stages of HIV-1 infection. In the present study, by an approach of combining serial dilutions of CD4 + T cells and T cell–cloning technologies, we are able to demonstrate that defective proviruses that persist in HIV-infected individuals during suppressive cART are translationally competent and produce the HIV-1 Gag and Nef proteins. The HIV-RNA transcripts expressed from these defective proviruses may trigger an element of innate immunity. Likewise, the viral proteins coded in the defective proviruses may form extracellular virus-like particles and may trigger immune responses. The persistent production of HIV-1 proteins in the absence of viral replication helps explain persistent immune activation despite HIV-1 levels below detection, and also presents new challenges to HIV-1 eradication.
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A multitude of studies showed that defective HIV-1 genomes inside cells may still produce individual viral transcripts or proteins, which could be mistaken as indicators of a functional reservoir of infectious virus.
“Conversely, a multitude of studies showed that defective HIV-1 genomes inside cells may still produce individual viral transcripts or proteins, 33-35,55 which could be mistaken as indicators of a functional reservoir of infectious virus.”
From Revealing viral and cellular dynamics of HIV-1 at the single-cell level during early treatment periods (2023) · cites this paper as [35]
The Abstract and Discussion report that defective, replication-incompetent HIV-1 proviruses can produce viral transcripts and proteins. Our copy does not address whether those products have been, or could be, mistaken for indicators of an infectious viral reservoir; that part of the claim is an inference rather than a point the paper makes. (LLM, conf=0.83)
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Cites
Fiji: an open-source platform for biological-image analysis
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2019 · Cited by 66,890 · see citing works
Gallo, R. C., Salahuddin, S. Z., Popovič, M., Shearer, G. M., Kaplan, M., Haynes, B. F., Palker, T. J., Redfield, R. R., Oleske, J. M., Safai, B., et al. (1984) · Science · doi:10.1126/science.6200936 · Cited by 3,639 · see citing works
. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection.
Kuller, L. H., Tracy, R., Belloso, W., Wit, S. D., Drummond, F., Lane, H. C., Ledergerber, B., Lundgren, J., Neuhaus, J., Nixon, D., et al. (2008) · PLoS Medicine · doi:10.1371/journal.pmed.0050203 · Cited by 1,617 · see citing works
Self-citationReplication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure
Ho, Y.-C., Shan, L., Hosmane, N. N., Wang, J., Laskey, S. B., Rosenbloom, D. I. S., Lai, J., Blankson, J. N., Siliciano, J. D., & Siliciano, R. F. (2013) · Cell · doi:10.1016/j.cell.2013.09.020 · Cited by 1,405 · see citing works
The accuracy of reverse transcriptase from HIV-1
Roberts, J. D., Bebenek, K., & Kunkel, T. A. (1988) · Science · doi:10.1126/science.2460925 · Cited by 997 · see citing works
Fidelity of HIV-1 reverse transcriptase
Preston, B. D., Poiesz, B. J., & Loeb, L. A. (1988) · Science · doi:10.1126/science.2460924 · Cited by 931 · see citing works
Defective proviruses rapidly accumulate during acute HIV-1 infection
Bruner, K. M., Murray, A. J., Pollack, R. A., Soliman, M. G., Laskey, S. B., Capoferri, A. A., Lai, J., Strain, M. C., Lada, S. M., Hoh, R., et al. (2016) · Nature Medicine · doi:10.1038/nm.4156 · Cited by 737 · see citing works
Shaw, G. M., Hahn, B. H., Arya, S. K., Groopman, J. E., Gallo, R. C., & Wong‐Staal, F. (1984) · Science · doi:10.1126/science.6095449 · Cited by 633 · see citing works
Absence of Detectable HIV-1 Viremia after Treatment Cessation in an Infant
Persaud, D., Gay, H., Ziemniak, C., Chen, Y. H., Piatak, M., Chun, T., Strain, M. C., Richman, D. D., & Luzuriaga, K. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1302976 · Cited by 580 · see citing works
HIV-1 Reverse TranscriptionPreprint
Hu, W.-S., & Hughes, S. H. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006882 · Cited by 515 · see citing works
Bullen, C. K., Laird, G. M., Durand, C. M., Siliciano, J. D., & Siliciano, R. F. (2014) · Nature Medicine · doi:10.1038/nm.3489 · Cited by 487 · see citing works
Li, Y., Kappes, J. C., Conway, J. A., Price, R. W., Shaw, G. M., & Hahn, B. H. (1991) · Journal of Virology · doi:10.1128/jvi.65.8.3973-3985.1991 · Cited by 378 · see citing works
Pollack, R. A., Jones, R. B., Pertea, M., Bruner, K. M., Martin, A. R., Thomas, A. S., Capoferri, A. A., Beg, S. A., Huang, S.-H., Karandish, S., et al. (2017) · Cell Host & Microbe · doi:10.1016/j.chom.2017.03.008 · Cited by 370 · see citing works
Imamichi, H., Dewar, R. L., Adelsberger, J. W., Rehm, C. A., O’Doherty, U., Paxinos, E. E., Fauci, A. S., & Lane, H. C. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1609057113 · Cited by 344 · see citing works
Self-citationBoulware, D. R., Hullsiek, K. H., Puronen, C. E., Rupert, A. W., Baker, J. V., French, M. A., Bohjanen, P. R., Novak, R. M., Neaton, J. D., & Sereti, I. (2011) · The Journal of Infectious Diseases · doi:10.1093/infdis/jir134 · Cited by 314 · see citing works
Buzón, M. J., Martín‐Gayo, E., Pereyra, F., Ouyang, Z., Sun, H., Li, J. Z., Piovoso, M. J., Shaw, A., Dalmau, J., Zangger, N., et al. (2014) · Journal of Virology · doi:10.1128/jvi.01046-14 · Cited by 277 · see citing works
Josefsson, L., von Stockenström, S., Faria, N. R., Sinclair, E., Bacchetti, P., Killian, M., Epling, L., Tan, A., Ho, T. N., Lemey, P., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1308313110 · Cited by 276 · see citing works
Repression of MHC Class I Gene Promoter Activity by Two-Exon Tat of HIV
Howcroft, T. K., Strebel, K., Martin, M. A., & Singer, D. S. (1993) · Science · doi:10.1126/science.8493575 · Cited by 223 · see citing works
HIV-1 DNA Decay Dynamics in Blood During More Than a Decade of Suppressive Antiretroviral Therapy
Besson, G. J., Lalama, C. M., Bosch, R. J., Gandhi, R. T., Bedison, M. A., Aga, E., Riddler, S. A., McMahon, D. K., Hong, F. F., & Mellors, J. W. (2014) · Clinical Infectious Diseases · doi:10.1093/cid/ciu585 · Cited by 217 · see citing works
Han, Y., Lin, Y. B., An, W., Xu, J., Yang, H., O’Connell, K. A., Dordai, D. I., Boeke, J. D., Siliciano, J. D., & Siliciano, R. F. (2008) · Cell Host & Microbe · doi:10.1016/j.chom.2008.06.008 · Cited by 214 · see citing works
Demystified . . . Human endogenous retroviruses
Nelson, P. N., Carnegie, P., Martin, J., Ejtehadi, H. D., Hooley, P., Roden, D., Rowland-Jones, S., Warren, P., Astley, J., & Murray, P. G. (2003) · Molecular Pathology · doi:10.1136/mp.56.1.11 · Cited by 210 · see citing works
Hohn, O., Hanke, K., & Bannert, N. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2013.00246 · Cited by 196 · see citing works
Sánchez, G., Xu, X., Chermann, J., & Hirsch, I. (1997) · Journal of Virology · doi:10.1128/jvi.71.3.2233-2240.1997 · Cited by 155 · see citing works
Kearney, M. F., Wiegand, A. P., Shao, W., Coffin, J. M., Mellors, J. W., Lederman, M. M., Gandhi, R. T., Keele, B. F., & Li, J. Z. (2015) · Journal of Virology · doi:10.1128/jvi.02139-15 · Cited by 149 · see citing works
Beneficial and detrimental effects of human endogenous retroviruses
Kurth, R., & Bannert, N. (2009) · International Journal of Cancer · doi:10.1002/ijc.24902 · Cited by 137 · see citing works
Risk of cancers during interrupted antiretroviral therapy in the SMART study
Silverberg, M. J., Neuhaus, J., Bower, M., Gey, D., Hatzakis, A. E., Henry, K., Hidalgo, J. A. M., Lourtau, L., Neaton, J. D., Tambussi, G., et al. (2007) · AIDS · doi:10.1097/qad.0b013e3282ed6338 · Cited by 137 · see citing works
HIV's evasion of the cellular immune response
Collins, K. L., & Baltimore, D. (1999) · Immunological Reviews · doi:10.1111/j.1600-065x.1999.tb01283.x · Cited by 126 · see citing works
Ferdin, J., Goričar, K., Dolžan, V., Plemenitaš, A., Martin, J. N., Peterlin, B. M., Deeks, S. G., & Lenassi, M. (2018) · PLoS ONE · doi:10.1371/journal.pone.0191613 · Cited by 103 · see citing works
Comprehensive analysis of unique cases with extraordinary control over HIV replication
Mendoza, D., Johnson, S., Peterson, B. A., Natarajan, V., Salgado, M., Dewar, R. L., Burbelo, P. D., Doria‐Rose, N. A., Graf, E. H., Greenwald, J. H., et al. (2012) · Blood · doi:10.1182/blood-2011-10-381996 · Cited by 93 · see citing works
Self-citationMurray, J. M., Zaunders, J. J., McBride, K. L., Xu, Y., Bailey, M., Suzuki, K., Cooper, D. A., Emery, S., Kelleher, A. D., & Koelsch, K. K. (2014) · Journal of Virology · doi:10.1128/jvi.03331-13 · Cited by 86 · see citing works
Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis
Young, G. R., Stoye, J. P., & Kassiotis, G. (2013) · BioEssays · doi:10.1002/bies.201300049 · Cited by 78 · see citing works
HIV-1 Nef: a master manipulator of the membrane trafficking machinery mediating immune evasion
Pawlak, E. N., & Dikeakos, J. D. (2015) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2015.01.003 · Cited by 73 · see citing works
HIV-1 Nef sequesters MHC-I intracellularly by targeting early stages of endocytosis and recycling
Dirk, B. S., Pawlak, E. N., Johnson, A. L., Nynatten, L. R. V., Jacob, R. A., Heit, B., & Dikeakos, J. D. (2016) · Scientific Reports · doi:10.1038/srep37021 · Cited by 67 · see citing works
Imamichi, H., Natarajan, V., Adelsberger, J. W., Rehm, C. A., Lempicki, R. A., Das, B., Hazen, A., Imamichi, T., & Lane, H. C. (2014) · AIDS · doi:10.1097/qad.0000000000000223 · Cited by 60 · see citing works
Self-citationMechanisms of HIV‐1 to escape from the host immune surveillance
Kamp, Berk, Visser, T. S. Q., & Nottet (2000) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.2000.00697.x · Cited by 43 · see citing works
Defective Virus Drives Human Immunodeficiency Virus Infection, Persistence, and Pathogenesis
Finzi, D., Plaeger, S. F., & Dieffenbach, C. W. (2006) · Clinical and Vaccine Immunology · doi:10.1128/cvi.00052-06 · Cited by 38 · see citing works
Intracellular Nef Detected in Peripheral Blood Mononuclear Cells from HIV Patients
Wang, T., Green, L. A., Gupta, S. K., Amet, T., Byrd, D., Yu, Q., Twigg, H. L., & Clauss, M. A. (2014) · AIDS Research and Human Retroviruses · doi:10.1089/aid.2013.0250 · Cited by 35 · see citing works
HIV DNA levels and decay in a cohort of 111 long-term virally suppressed patients
Golob, J. L., Stern, J., Holte, S., Kitahata, M. M., Crane, H. M., Coombs, R. W., Goecker, E. A., Woolfrey, A. E., & Harrington, R. D. (2018) · AIDS · doi:10.1097/qad.0000000000001948 · Cited by 34 · see citing works
Single Vector System for Efficient N-myristoylation of Recombinant Proteins in E. coli
Glück, J. M., Hoffmann, S., Koenig, B. W., & Willbold, D. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010081 · Cited by 33 · see citing works
Xufré, C., Costa, M., Roura‐Mir, C., Busqueta, E. C., Usero, L., Pizarro, E., Obiols, G., Jaraquemada, D., & Martı́, M. (2013) · International Immunology · doi:10.1093/intimm/dxt020 · Cited by 32 · see citing works
Pasternak, A. O., DeMaster, L. K., Kootstra, N. A., Reiss, P., O’Doherty, U., & Berkhout, B. (2015) · Journal of Virology · doi:10.1128/jvi.02597-15 · Cited by 27 · see citing works
Mann, J. K., Chopera, D., Omarjee, S., Kuang, X. T., Le, A. Q., Anmole, G., Danroth, R., Mwimanzi, P., Reddy, T., Carlson, J. M., et al. (2014) · Virology · doi:10.1016/j.virol.2014.08.009 · Cited by 26 · see citing works
Effects of HIV-1 Nef on Human N-Myristoyltransferase 1
Morgan, C. R., Miglionico, B. V., & Engen, J. R. (2011) · Biochemistry · doi:10.1021/bi200197e · Cited by 21 · see citing works
Takebe, Y., & Telesnitsky, A. (2006) · Virology · doi:10.1016/j.virol.2006.05.009 · Cited by 8 · see citing works
Imai, H., Maotani, K., Yeon-Sil, S. H. I. N., Ikuta, K., Suehiro, S., Kurimura, T., Kato, S., & Hirai, K. (1991) · Virus Genes · doi:10.1007/bf00571734 · Cited by 7 · see citing works
Flagged first, then by citations
1 of the 46 references couldn’t be matched to a known paper.
Cited by
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Research priorities for an HIV cure: International AIDS Society Global Scientific Strategy 2021
Deeks, S. G., Archin, N., Cannon, P., Collins, S., Jones, R. B., de Jong, M. A. W. P., Lambotte, O., Lamplough, R., Ndung’u, T., Sugarman, J., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01590-5 · Cited by 377 · see citing works
The Biology of the HIV-1 Latent Reservoir and Implications for Cure Strategies
Cohn, L. B., Chomont, N., & Deeks, S. G. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.03.014 · Cited by 280 · see citing works
Prevention, treatment and cure of HIV infection
Landovitz, R. J., Scott, H. M., & Deeks, S. G. (2023) · Nature Reviews Microbiology · doi:10.1038/s41579-023-00914-1 · Cited by 145 · see citing works
Recommendations for measuring HIV reservoir size in cure-directed clinical trials
Abdel‐Mohsen, M., Richman, D. D., Siliciano, R. F., Nussenzweig, M. C., Howell, B. J., Martínez‐Picado, J., Chomont, N., Bar, K. J., Yu, X. G., Lichterfeld, M. D., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-1022-1 · Cited by 132 · see citing works
McMyn, N. F., Varriale, J., Fray, E. J., Zitzmann, C., Macleod, H. H. B., Lai, J., Singhal, A., Moskovljevic, M., Garcia, M. A., Lopez, B. M., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci171554 · Cited by 130 · see citing works
Progressive transformation of the HIV-1 reservoir cell profile over two decades of antiviral therapy
Lian, X., Seiger, K. W., Parsons, E. M., Gao, C., Sun, W., Gladkov, G. T., Roseto, I. C., Einkauf, K. B., Osborn, M. R., Chevalier, J. M., et al. (2023) · Cell Host & Microbe · doi:10.1016/j.chom.2022.12.002 · Cited by 116 · see citing works
Simonetti, F. R., White, J. A., Tumiotto, C., Ritter, K. D., Cai, M., Gandhi, R. T., Deeks, S. G., Howell, B. J., Montaner, L. J., Blankson, J. N., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2006816117 · Cited by 109 · see citing works
Profound phenotypic and epigenetic heterogeneity of the HIV-1-infected CD4+ T cell reservoir
Wu, V. H., Nordin, J. M. L., Nguyen, S., Joy, J. P., Mampe, F., Estrada, P. M. D. R., Torres-Ruiz, F., González-Navarro, M., Luna-Villalobos, Y. A., Ávila‐Ríos, S., et al. (2022) · Nature Immunology · doi:10.1038/s41590-022-01371-3 · Cited by 99 · see citing works
Lian, X., Gao, C., Sun, X., Jiang, C., Einkauf, K. B., Seiger, K. W., Chevalier, J. M., Yuki, Y., Martin, M. P., Hoh, R., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abl4097 · Cited by 96 · see citing works
The multifaceted nature of HIV latency
Dufour, C., Gantner, P., Fromentin, R., & Chomont, N. (2020) · Journal of Clinical Investigation · doi:10.1172/jci136227 · Cited by 94 · see citing works
Immunological approaches to HIV cure
Ward, A. R., Mota, T. M., & Jones, R. B. (2020) · Seminars in Immunology · doi:10.1016/j.smim.2020.101412 · Cited by 92 · see citing works
Mechanisms underlying HIV-associated cognitive impairment and emerging therapies for its management
Ellis, R. J., Marquine, M. J., Kaul, M., Fields, J. A., & Schlachetzki, J. C. M. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00879-y · Cited by 98 · see citing works
White, J. A., Wu, F., Yasin, S., Moskovljevic, M., Varriale, J., Dragoni, F., Camilo-Contreras, A., Duan, J., Zheng, M. Y., Tadzong, N. F., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci165245 · Cited by 86 · see citing works
Intact HIV Proviruses Persist in the Brain Despite Viral Suppression with ART
Cochrane, C. R., Angelovich, T. A., Byrnes, S. J., Waring, E., Guanizo, A. C., Trollope, G. S., Zhou, J., Vue, J., Senior, L., Wanicek, E., et al. (2022) · Annals of Neurology · doi:10.1002/ana.26456 · Cited by 84 · see citing works
Dubé, M., Tastet, O., Dufour, C., Sannier, G., Brassard, N., Ortega-Delgado, G.-G., Pagliuzza, A., Richard, C., Nayrac, M., Routy, J., et al. (2023) · Cell Host & Microbe · doi:10.1016/j.chom.2023.08.006 · Cited by 87 · see citing works
Cho, A., Gaebler, C., Olveira, T., Ramos, V., Saad, M., Lorenzi, J. C. C., Gazumyan, A., Moir, S. L., Caskey, M. F., Chun, T., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2117630119 · Cited by 76 · see citing works
Duette, G., Hiener, B., Morgan, H., Mazur, F. G., Mathivanan, V., Horsburgh, B. A., Fisher, K., Tong, O., Lee, E., Ahn, H., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci154422 · Cited by 75 · see citing works
Phenotypic analysis of the unstimulated in vivo HIV CD4 T cell reservoir
Neidleman, J. A., Luo, X., Frouard, J., Xie, G., Hsiao, F., Ma, T., Morcilla, V., Lee, A., Telwatte, S., Thomas, R., et al. (2020) · eLife · doi:10.7554/elife.60933 · Cited by 78 · see citing works
Residual immune dysfunction under antiretroviral therapy
Cai, C. W., & Sereti, I. (2021) · Seminars in Immunology · doi:10.1016/j.smim.2021.101471 · Cited by 80 · see citing works
Cole, B., Lambrechts, L., Gantner, P., Noppe, Y., Bonine, N., Witkowski, W., Chen, L., Palmer, S., Mullins, J. I., Chomont, N., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24080-1 · Cited by 75 · see citing works
Non-invasive plasma glycomic and metabolic biomarkers of post-treatment control of HIV
Giron, L. B., Palmer, C. S., Liu, Q., Yin, X., Papasavvas, E., Sharaf, R. R., Etemad, B., Damra, M., Goldman, A. R., Tang, H., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24077-w · Cited by 73 · see citing works
Stevenson, E. M., Ward, A. R., Truong, R., Thomas, A. S., Huang, S.-H., Dilling, T. R., Terry, S. N., Bui, J. K., Mota, T. M., Danesh, A., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.142640 · Cited by 65 · see citing works
The multifaceted nature of HIV latency
Dufour, C., Gantner, P., Fromentin, R., & Chomont, N. (2021) · Journal of Clinical Investigation · doi:10.1172/jci151380 · Cited by 63 · see citing works
Singh, K., Natarajan, V., Dewar, R. L., Rupert, A. W., Badralmaa, Y., Zhai, T., Winchester, N., Scrimieri, F., Smith, M., Davis, I., et al. (2023) · AIDS · doi:10.1097/qad.0000000000003667 · Cited by 60 · see citing works
Self-citationHIV Persistence, Latency, and Cure Approaches: Where Are We Now?
Chou, T. C., Maggirwar, N. S., & Marsden, M. D. (2024) · Viruses · doi:10.3390/v16071163 · Cited by 66 · see citing works
Insights Into Persistent HIV-1 Infection and Functional Cure: Novel Capabilities and Strategies
Ta, T. M., Malik, S., Anderson, E. M., Jones, A. D., Perchik, J., Freylikh, M., Sardo, L., Klase, Z. A., & Izumi, T. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.862270 · Cited by 57 · see citing works
Self-citationVaillant, A. (2020) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.0c00638 · Cited by 59 · see citing works
Takata, H., Mitchell, J. L., Pacheco, J. A., Pagliuzza, A., Pinyakorn, S., Buranapraditkun, S., Sacdalan, C., Leyre, L., Nathanson, S., Kakazu, J. C., et al. (2023) · Cell Host & Microbe · doi:10.1016/j.chom.2023.08.012 · Cited by 55 · see citing works
Sannier, G., Dubé, M., Dufour, C., Richard, C., Brassard, N., Ortega-Delgado, G.-G., Pagliuzza, A., Baxter, A. E., Niessl, J., Brunet‐Ratnasingham, E., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109643 · Cited by 55 · see citing works
NF-κB sub-pathways and HIV cure: A revisit
Wong, L. M., & Jiang, G. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.103159 · Cited by 52 · see citing works
The cell biology of HIV-1 latency and rebound
Mbonye, U. R., & Karn, J. (2024) · Retrovirology · doi:10.1186/s12977-024-00639-w · Cited by 51 · see citing works
Li, C., Mori, L., & Valente, S. T. (2020) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiaa681 · Cited by 42 · see citing works
Dufour, C., Richard, C., Pardons, M., Massanella, M., Ackaoui, A., Murrell, B., Routy, B., Thomas, R., Routy, J., Fromentin, R., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36772-x · Cited by 43 · see citing works
Low Inducibility of Latent Human Immunodeficiency Virus Type 1 Proviruses as a Major Barrier to Cure
Siliciano, J. D., & Siliciano, R. F. (2020) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiaa649 · Cited by 45 · see citing works
Zerbato, J. M., Khoury, G., Zhao, W. D., Gartner, M. J., Pascoe, R. D., Rhodes, A., Dantanarayana, A., Gooey, M., Anderson, J. L., Bacchetti, P., et al. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103241 · Cited by 44 · see citing works
Defective HIV-1 genomes and their potential impact on HIV pathogenesis
Kuniholm, J., Coote, C., & Henderson, A. J. (2022) · Retrovirology · doi:10.1186/s12977-022-00601-8 · Cited by 45 · see citing works
Lau, C., Adan, M. A., & Maldarelli, F. M. (2021) · Viruses · doi:10.3390/v13122512 · Cited by 44 · see citing works
HIV-1 Reservoir Persistence and Decay: Implications for Cure Strategies
Kreider, E. F., & Bar, K. J. (2022) · Current HIV/AIDS Reports · doi:10.1007/s11904-022-00604-2 · Cited by 45 · see citing works
Suzuki, K., Zaunders, J. J., Gates, T. M., Levert‐Mignon, A., Butterly, S., Liu, Z., Ishida, T., Palmer, S., Rae, C. D., Jugé, L., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2210584119 · Cited by 43 · see citing works
Pardons, M., Cole, B., Lambrechts, L., van Snippenberg, W., Rutsaert, S., Noppe, Y., Langhe, N. D., Dhondt, A., Vega, J. B., Eyassu, F., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-44020-5 · Cited by 43 · see citing works
Impact of misclassified defective proviruses on HIV reservoir measurements
Reeves, D. B., Gaebler, C., Oliveira, T. Y., Peluso, M. J., Schiffer, J. T., Cohn, L. B., Deeks, S. G., & Nussenzweig, M. C. (2023) · Nature Communications · doi:10.1038/s41467-023-39837-z · Cited by 40 · see citing works
Persistence of viral RNA in lymph nodes in ART-suppressed SIV/SHIV-infected Rhesus Macaques
Cadena, A. M., Ventura, J. D., Abbink, P., Borducchi, E. N., Tuyishime, H., Mercado, N. B., Walker-Sperling, V. E. K., Siamatu, M., Liu, P.-T., Chandrashekar, A., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21724-0 · Cited by 37 · see citing works
HIV persistence: silence or resistance?
Pasternak, A. O., & Berkhout, B. (2023) · Current Opinion in Virology · doi:10.1016/j.coviro.2023.101301 · Cited by 37 · see citing works
Emert‐Sedlak, L. A., Tice, C. M., Shi, H., Alvarado, J. J., Shu, S. T., Reitz, A. B., & Smithgall, T. E. (2024) · Cell chemical biology · doi:10.1016/j.chembiol.2024.02.004 · Cited by 36 · see citing works
Benlarbi, M., Richard, J., Bourassa, C., Tolbert, W. D., Chartrand‐Lefebvre, C., Gendron‐Lepage, G., Sylla, M., Far, M. E., Messier-Peet, M., Guertin, C., et al. (2023) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiad503 · Cited by 35 · see citing works
HIV transcription persists in the brain of virally suppressed people with HIV
Eddine, J. J., Angelovich, T. A., Zhou, J., Byrnes, S. J., Tumpach, C., Saraya, N., Chalmers, E. K., Shepherd, R. A., Tan, A. E. Q., Marinis, S., et al. (2024) · PLoS Pathogens · doi:10.1371/journal.ppat.1012446 · Cited by 35 · see citing works
Cole, B., Lambrechts, L., Boyer, Z., Noppe, Y., Scheerder, M. D., Eden, J., Vrancken, B., Schlub, T. E., McLaughlin, S., Frenkel, L. M., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110739 · Cited by 35 · see citing works
Biotypes of HIV-associated neurocognitive disorders based on viral and immune pathogenesis
Johnson, T. P., & Nath, A. (2022) · Current Opinion in Infectious Diseases · doi:10.1097/qco.0000000000000825 · Cited by 35 · see citing works
Passaes, C., Delagreverie, H. M., Avettand-Fènoël, V., David, A., Monceaux, V., Essat, A., Müller-Trutwin, M. C., Duffy, D., Castro, N. D., Wittkop, L., et al. (2021) · Journal of Virology · doi:10.1128/jvi.00016-21 · Cited by 34 · see citing works
Angelovich, T. A., Cochrane, C. R., Zhou, J., Tumpach, C., Byrnes, S. J., Eddine, J. J., Waring, E., Busman‐Sahay, K., Deléage, C., Jenkins, T. A., et al. (2023) · Annals of Neurology · doi:10.1002/ana.26750 · Cited by 33 · see citing works
Obregon-Perko, V., Bricker, K. M., Mensah, G., Uddin, F., Kumar, M. R., Fray, E. J., Siliciano, R. F., Schoof, N., Horner, A. M., Mavigner, M., et al. (2020) · Journal of Virology · doi:10.1128/jvi.01669-20 · Cited by 33 · see citing works
Ellis, R. J., Iudicello, J. E., Heaton, R. K., Isnard, S., Lin, J. C.-Y., Routy, J., Gianella, S., Hoenigl, M., & Knight, R. D. (2021) · Viruses · doi:10.3390/v13101891 · Cited by 33 · see citing works
Next-generation bNAbs for HIV-1 cure strategies
Schriek, A. I., Aldon, Y., van Gils, M. J., & de Taeye, S. W. (2023) · Antiviral Research · doi:10.1016/j.antiviral.2023.105788 · Cited by 27 · see citing works
HIV-1 Persistence and Chronic Induction of Innate Immune Responses in Macrophages
Akiyama, H., & Gummuluru, S. (2020) · Viruses · doi:10.3390/v12070711 · Cited by 29 · see citing works
Correlation of SARS‑CoV‑2 to cancer: Carcinogenic or anticancer? (Review)
Li, Y., Ren, H.-C., & Cao, J.-H. (2022) · International Journal of Oncology · doi:10.3892/ijo.2022.5332 · Cited by 32 · see citing works
Papasavvas, E., Azzoni, L., Ross, B. N., Fair, M. G., Yuan, Z., Gyampoh, K., Mackiewicz, A., Sciorillo, A., Pagliuzza, A., Lada, S. M., et al. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa809 · Cited by 28 · see citing works
Wu, G., Zuck, P. D., Goh, S. L., Milush, J. M., Vohra, P., Wong, J. K., Somsouk, M., Yukl, S. A., Shacklett, B. L., Chomont, N., et al. (2021) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiab121 · Cited by 28 · see citing works
Plasma-Derived HIV-1 Virions Contain Considerable Levels of Defective Genomes
Fisher, K., Wang, X. Q., Lee, A., Morcilla, V., de Vries, A., Lee, E., Eden, J., Deeks, S. G., Kelleher, A. D., & Palmer, S. (2022) · Journal of Virology · doi:10.1128/jvi.02011-21 · Cited by 28 · see citing works
Low Level Viremia Is Associated With Serious non-AIDS Events in People With HIV
Ganesan, A., Hsieh, H.-C., Chu, X., Colombo, R. E., Berjohn, C. M., Lalani, T., Yabes, J., Joya, C. A., Blaylock, J. M., & Agan, B. K. (2024) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofae147 · Cited by 26 · see citing works
Pasternak, A. O., Vroom, J., Kootstra, N. A., Wit, F. W. N. M., de Bruin, M., Francesco, D. D., Bakker, M. E., Sabin, C. A., Winston, A., Prins, J. M., et al. (2021) · eLife · doi:10.7554/elife.68174 · Cited by 25 · see citing works
Intragenic proviral elements support transcription of defective HIV-1 proviruses
Kuniholm, J., Armstrong, E. M. R., Bernabe, B., Coote, C., Berenson, A., Drinan, S. D., Olson, A. J., He, X., Lin, N., Bass, J. I. F., et al. (2021) · PLoS Pathogens · doi:10.1371/journal.ppat.1009982 · Cited by 23 · see citing works
Trained Immunity and HIV Infection
Sviridov, D., Miller, Y. I., & Bukrinsky, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.903884 · Cited by 27 · see citing works
Persistent HIV-1 transcription during ART: time to reassess its significance?
Fombellida-Lopez, C., Berkhout, B., Darcis, G., & Pasternak, A. O. (2024) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0000000000000849 · Cited by 24 · see citing works
Wu, G., Cheney, C. A., Huang, Q., Hazuda, D. J., Howell, B. J., & Zuck, P. D. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.636703 · Cited by 24 · see citing works
Huang, Y., Dhummakupt, A., Khetan, P., Nilles, T. L., Zhou, W., Mudvari, P., Szewczyk, J., Chen, Y. H., Boritz, E., Ji, H., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1007626 · Cited by 24 · see citing works
Clercq, J. D., Scheerder, M. D., Mortier, V., Verhofstede, C., Vandecasteele, S. J., Allard, S. D., Necsoi, C., Wit, S. D., Gerlo, S., & Vandekerckhove, L. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1337316 · Cited by 23 · see citing works
The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers
Gasca‐Capote, C., Lian, X., Gao, C., Roseto, I. C., Jiménez‐León, M. R., Gladkov, G. T., Camacho-Sojo, M. I., Pérez‐Gómez, A., Gallego, I., López-Cortés, L. E., et al. (2024) · Journal of Clinical Investigation · doi:10.1172/jci174215 · Cited by 23 · see citing works
Darcis, G., Berkhout, B., & Pasternak, A. O. (2020) · Viruses · doi:10.3390/v12050489 · Cited by 24 · see citing works
Sialyl-LewisX Glycoantigen Is Enriched on Cells with Persistent HIV Transcription during Therapy
Colomb, F., Giron, L. B., Kuri-Cervantes, L., Adeniji, O. S., Ma, T., Dweep, H., Battivelli, E., Verdin, E. M., Palmer, C. S., Tateno, H., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107991 · Cited by 22 · see citing works
Bone Quality in Relation to HIV and Antiretroviral Drugs
Olali, A. Z., Carpenter, K. A., Myers, M., Sharma, A., Yin, M. T., Al‐Harthi, L., & Ross, R. D. (2022) · Current HIV/AIDS Reports · doi:10.1007/s11904-022-00613-1 · Cited by 23 · see citing works
Learning from Persistent Viremia: Mechanisms and Implications for Clinical Care and HIV-1 Cure
Wu, F., & Simonetti, F. R. (2023) · Current HIV/AIDS Reports · doi:10.1007/s11904-023-00674-w · Cited by 21 · see citing works
Flow Virometry Quantification of Host Proteins on the Surface of HIV-1 Pseudovirus Particles
Burnie, J., Tang, V. A., Welsh, J. A., Persaud, A. T., Thaya, L., Jones, J. C., & Guzzo, C. (2020) · Viruses · doi:10.3390/v12111296 · Cited by 22 · see citing works
HIV Compartmentalization in the CNS and Its Impact in Treatment Outcomes and Cure Strategies
Chan, P., & Spudich, S. (2022) · Current HIV/AIDS Reports · doi:10.1007/s11904-022-00605-1 · Cited by 22 · see citing works
Sarabia, I., Huang, S.-H., Ward, A. R., Jones, R. B., & Bosque, A. (2021) · Journal of Virology · doi:10.1128/jvi.01297-20 · Cited by 21 · see citing works
Byrnes, S. J., Eddine, J. J., Zhou, J., Chalmers, E. K., Wanicek, E., Osman, N., Jenkins, T. A., Roche, M., Brew, B. J., Estes, J. D., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1570692 · Cited by 21 · see citing works
HIV reservoirs are dominated by genetically younger and clonally enriched proviruses
Kinloch, N. N., Shahid, A., Dong, W., Kirkby, D., Jones, B. R., Beelen, C. J., MacMillan, D., Lee, G. Q., Mota, T. M., Sudderuddin, H., et al. (2023) · mBio · doi:10.1128/mbio.02417-23 · Cited by 21 · see citing works
Scrimieri, F., Bastian, E., Smith, M., Rehm, C. A., Morse, C. G., Kuruppu, J. C., McLaughlin, M. E., Chang, W., Sereti, I., Kovacs, J. A., et al. (2024) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiae009 · Cited by 21 · see citing works
Self-citationChronic HIV Transcription, Translation, and Persistent Inflammation
Kilroy, J. M., Leal, A. A., & Henderson, A. J. (2024) · Viruses · doi:10.3390/v16050751 · Cited by 21 · see citing works
The Splice of Life: Does RNA Processing Have a Role in HIV-1 Persistence?
Pasternak, A. O., & Berkhout, B. (2021) · Viruses · doi:10.3390/v13091751 · Cited by 20 · see citing works
Villar, S. S., López‐Huertas, M. R., Jiménez, D., Galera, C., Martínez‐Sanz, J., Moreno, E., Muriel, A., Gutiérrez, F., Busca, C., Portilla, J., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.848630 · Cited by 19 · see citing works
Subtype C HIV-1 reservoirs throughout the body in ART-suppressed individuals
Liu, Z., Julius, P., Kang, G., West, J. T., & Wood, C. A. (2022) · JCI Insight · doi:10.1172/jci.insight.162604 · Cited by 19 · see citing works
The latent HIV reservoir: current advances in genetic sequencing approaches
Moar, P., Premeaux, T. A., Atkins, A., & Ndhlovu, L. C. (2023) · mBio · doi:10.1128/mbio.01344-23 · Cited by 19 · see citing works
SuPAR mediates viral response proteinuria by rapidly changing podocyte function
Wei, C., Datta, P. K., Siegerist, F., Li, J., Sudhini, Y. R., Koh, K. H., Kriho, N., Ismail, A., Luo, S., Fischer, T., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-40165-5 · Cited by 18 · see citing works
Delporte, M., Lambrechts, L., Blomme, E. E., van Snippenberg, W., Rutsaert, S., Verschoore, M., Smet, E. D., Noppe, Y., Langhe, N. D., Scheerder, M. D., et al. (2024) · Clinical Chemistry · doi:10.1093/clinchem/hvae192 · Cited by 18 · see citing works
Vellas, C., Nayrac, M., Collercandy, N., Requena, M., Jeanne, N., Latour, J., Dimeglio, C., Cazabat, M., Barange, K., Alric, L., et al. (2024) · eBioMedicine · doi:10.1016/j.ebiom.2023.104954 · Cited by 17 · see citing works
Thorball, C., Borghesi, A., Bachmann, N., von Siebenthal, C., Vongrad, V., Turk, T., Neumann, K., Beerenwinkel, N., Bogojeska, J., Röth, V., et al. (2020) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0000000000002473 · Cited by 15 · see citing works
Buchholtz, N. V., Hermans, L. E., Umunnakwe, C. N., Nühn, M. M., Voss, R., Need, E., Kootstra, N. A., Maurer, I., de Jong, D. C. M., Symons, J., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1484358 · Cited by 16 · see citing works
Immunotherapeutic approaches to HIV cure and remission
Lee, M. J., Fidler, S. J., & Frater, J. (2021) · Current Opinion in Infectious Diseases · doi:10.1097/qco.0000000000000803 · Cited by 16 · see citing works
Chronic and delayed neurological manifestations of persistent infections
Pandya, D., & Johnson, T. P. (2023) · Current Opinion in Neurology · doi:10.1097/wco.0000000000001154 · Cited by 17 · see citing works
Phenotyping Viral Reservoirs to Reveal HIV-1 Hiding Places
Chen, W., Berkhout, B., & Pasternak, A. O. (2025) · Current HIV/AIDS Reports · doi:10.1007/s11904-025-00723-6 · Cited by 15 · see citing works
Viral and Host Biomarkers of HIV Remission Post Treatment Interruption
Giron, L. B., & Abdel‐Mohsen, M. (2022) · Current HIV/AIDS Reports · doi:10.1007/s11904-022-00607-z · Cited by 15 · see citing works
Guo, S., Luke, B. T., Henry, A. R., Darko, S. W., Brandt, L. D., Su, L., Sun, D. F., Wells, D., Joseph, K. W., Demirov, D. G., et al. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010726 · Cited by 15 · see citing works
HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing
Lyons, D. E., Kumar, P., Roan, N. R., Defechereux, P. A., Feschotte, C., Lange, U. C., Murthy, N., Sameshima, P., Verdin, E. M., Ake, J. A., et al. (2023) · Viruses · doi:10.3390/v15112171 · Cited by 15 · see citing works
Silencing the transcriptionally active HIV reservoir to improve treatment outcomes
Kazmierski, J., Tavora, R., O’Brien, R. L. F., Schulze‐Gahmen, U., Boehm, D., Roan, N. R., Nixon, D. F., Ndhlovu, L. C., Valente, S. T., & Ott, M. (2024) · Nature Microbiology · doi:10.1038/s41564-024-01816-5 · Cited by 15 · see citing works
Puertas, M. C., Bayón-Gil, Á., García-Guerrero, M. C., Salgado, M., Urrea, V., Morón‐López, S., Peña, R., Jiménez‐Moyano, E., Clotet, B., Prado, J. G., et al. (2021) · mBio · doi:10.1128/mbio.00560-21 · Cited by 15 · see citing works
Stern, J., Solomon, A. E., Dantanarayana, A., Pascoe, R. D., Reynaldi, A., Davenport, M. P., Milush, J. M., Deeks, S. G., Hartogensis, W., Hecht, F. M., et al. (2021) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiab533 · Cited by 15 · see citing works
The HIV-1 Matrix Protein p17 Does Cross the Blood-Brain Barrier
Caccuri, F., Neves, V., Gano, L., Correia, J. D. G., Oliveira, M. C., Mazzuca, P., Caruso, A., & Castanho, M. A. R. B. (2021) · Journal of Virology · doi:10.1128/jvi.01200-21 · Cited by 15 · see citing works
A widely distributed HIV-1 provirus elimination assay to evaluate latency-reversing agents in vitro
Matsuda, K., Islam, S., Takada, T., Tsuchiya, K., Tan, B. J. Y., Hattori, S.-I., Katsuya, H., Kitagawa, K., Kim, K. S., Matsuo, M., et al. (2021) · Cell Reports Methods · doi:10.1016/j.crmeth.2021.100122 · Cited by 15 · see citing works
Johnson, S. D., Fox, H. S., Buch, S. J., & Byrareddy, S. N. (2021) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-021-09993-4 · Cited by 14 · see citing works
Mesenchymal Stromal Cells: a Possible Reservoir for HIV-1?
Kallmeyer, K., Ryder, M. A., & Pepper, M. S. (2022) · Stem Cell Reviews and Reports · doi:10.1007/s12015-021-10298-5 · Cited by 14 · see citing works
- Authors
- Imamichi, H., Smith, M., Adelsberger, J. W., Izumi, T., Scrimieri, F., Sherman, B. T., Rehm, C. A., Imamichi, T., Pau, A., Catalfamo, M., Fauci, A. S., & Lane, H. C.
- Affiliations
- National Institutes of Health (US)
- Frederick National Laboratory for Cancer Research (US)
- Department of Microbiology and Immunology, Georgetown University School of Medicine, Washington, DC 20057
- Corresponding author
- Fauci, Anthony S.
- Lane, H. Clifford
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2020-02-06
- Volume
- 117
- Issue
- 7
- Pages
- 3704-3710
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC7035625
- OpenAlex
- W3005267901
- Cited by
- 251
- References
- 46
- Citations by year
- 2026: 38 · 2025: 41 · 2024: 40 · 2023: 41 · 2022: 33 · 2021: 38 · 2020: 19
- FWCI
- 17.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases (N/A)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Keywords
- HIV-1 Gag protein, HIV-1 Nef, CD4+ T cells, highly active antiretroviral therapy, viral persistence, open reading frames, virus-like particles, innate immunity, persistent immune activation, HIV-1 eradication
- MeSH terms
- Humans, Leukocytes, Mononuclear, Male, Middle Aged, Proviruses, Viral Proteins, CD4-Positive T-Lymphocytes, HIV-1, HIV Infections
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