Extremely High Mutation Rate of HIV-1 In Vivo

Cuevas, José M.; Geller, Ron; Garijo, Raquel; López-Aldeguer, José; Sanjuán, Rafael

doi:10.1371/journal.pbio.1002251

Cited by 371HIV Research and TreatmentEvolution and Genetic DynamicsRNA regulation and disease

Extremely High Mutation Rate of HIV-1 In Vivo

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Cuevas, José M., Geller, Ron, Garijo, Raquel, López-Aldeguer, José, Sanjuán, Rafael·2015·PLOS Biology

DOI 10.1371/journal.pbio.1002251PMC PMC4574155

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Abstract

Rates of spontaneous mutation critically determine the genetic diversity and evolution of RNA viruses. Although these rates have been characterized in vitro and in cell culture models, they have seldom been determined in vivo for human viruses. Here, we use the intrapatient frequency of premature stop codons to quantify the HIV-1 genome-wide rate of spontaneous mutation in DNA sequences from peripheral blood mononuclear cells. This reveals an extremely high mutation rate of (4.1 ± 1.7) × 10-3 per base per cell, the highest reported for any biological entity. Sequencing of plasma-derived sequences yielded a mutation frequency 44 times lower, indicating that a large fraction of viral genomes are lethally mutated and fail to reach plasma. We show that the HIV-1 reverse transcriptase contributes only 2% of mutations, whereas 98% result from editing by host cytidine deaminases of the A3 family. Hypermutated viral sequences are less abundant in patients showing rapid disease progression compared to normal progressors, highlighting the antiviral role of A3 proteins. However, the amount of A3-mediated editing varies broadly, and we find that low-edited sequences are more abundant among rapid progressors, suggesting that suboptimal A3 activity might enhance HIV-1 genetic diversity and pathogenesis.

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Each pathogen poses a unique set of challenges, including high lethality, rapid mutations, immune evasion, new strains and variants.
“Each pathogen poses a unique set of challenges, including high lethality, rapid mutations, immune evasion, new strains and variants252–258.”
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Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400 · see citing works
Quality control and preprocessing of metagenomic datasets
Schmieder, R., & Edwards, R. A. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr026 · Cited by 4,989 · see citing works
Prognosis in HIV-1 Infection Predicted by the Quantity of Virus in Plasma
Mellors, J. W., Rinaldo, C. R., Gupta, P., White, R. M., Todd, J. A., & Kingsley, L. (1996) · Science · doi:10.1126/science.272.5265.1167 · Cited by 2,658 · see citing works
J. Virol. Methods
Singh, R. P., Kurz, J., & Boiteau, G. (1996) · Journal of Virological Methods · doi:10.1016/0166-0934(96)02096-4 · Cited by 2,554 · see citing works
Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection
Keele, B. F., Giorgi, E. E., Salazar-Gonzalez, J. F., Decker, J. M., Pham, K. T., Salazar, M. G., Sun, C., Grayson, T. B., Wang, S., Li, H., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802203105 · Cited by 1,913 · see citing works
Replication-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
Viral Mutation Rates
Sanjuán, R., Nebot, M. R., Chirico, N., Mansky, L. M., & Belshaw, R. D. (2010) · Journal of Virology · doi:10.1128/jvi.00694-10 · Cited by 1,247 · see citing works
Self-citation
Lower in vivo mutation rate of human immunodeficiency virus type 1 than that predicted from the fidelity of purified reverse transcriptase
Mansky, L. M., & Temin, H. M. (1995) · Journal of Virology · doi:10.1128/jvi.69.8.5087-5094.1995 · Cited by 1,154 · see citing works
Quasispecies diversity determines pathogenesis through cooperative interactions in a viral population
Vignuzzi, M., Stone, J. K., Arnold, J. J., Cameron, C. E., & Andino, R. (2006) · Nature · doi:10.1038/nature04388 · Cited by 1,116 · 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
Modelling viral and immune system dynamics
Perelson, A. S. (2002) · Nature reviews. Immunology · doi:10.1038/nri700 · Cited by 949 · see citing works
Deciphering Human Immunodeficiency Virus Type 1 Transmission and Early Envelope Diversification by Single-Genome Amplification and Sequencing
Salazar-Gonzalez, J. F., Bailes, E., Pham, K. T., Salazar, M. G., Guffey, M. B., Keele, B. F., Derdeyn, C. A., FARMER, P. K., Hunter, E., Allen, S., et al. (2008) · Journal of Virology · doi:10.1128/jvi.02660-07 · Cited by 587 · see citing works
Multiple, Linked Human Immunodeficiency Virus Type 1 Drug Resistance Mutations in Treatment-Experienced Patients Are Missed by Standard Genotype Analysis
Palmer, S., Kearney, M., Maldarelli, F., Halvas, E. K., Bixby, C. J., Bazmi, H., Rock, D., Falloon, J., Davey, R. T., Dewar, R. L., et al. (2005) · Journal of Clinical Microbiology · doi:10.1128/jcm.43.1.406-413.2005 · Cited by 506 · see citing works
The Evolution and Emergence of RNA Viruses
Holmes, E. C. (2009) · doi:10.1093/oso/9780199211128.001.0001 · Cited by 459 · see citing works
Biased hypermutation and other genetic changes in defective measles viruses in human brain infections
Cattaneo, R., Schmid, A., Eschle, D., et al. (1988) · Cell · doi:10.1016/0092-8674(88)90048-7 · Cited by 439 · see citing works
Increased Fidelity Reduces Poliovirus Fitness and Virulence under Selective Pressure in Mice
Pfeiffer, J. K., & Kirkegaard, K. (2005) · PLoS Pathogens · doi:10.1371/journal.ppat.0010011 · Cited by 383 · see citing works
The role of mutational robustness in RNA virus evolution
Lauring, A. S., Frydman, J., & Andino, R. (2013) · Nature Reviews Microbiology · doi:10.1038/nrmicro3003 · Cited by 354 · see citing works
Predictors of disease progression in HIV infection: a review
Langford, S. E., Ananworanich, J., & Cooper, D. A. (2007) · AIDS Research and Therapy · doi:10.1186/1742-6405-4-11 · Cited by 336 · see citing works
Evidence for Editing of Human Papillomavirus DNA by APOBEC3 in Benign and Precancerous Lesions
Vartanian, J., Guétard, D., Henry, M., & Wain–Hobson, S. (2008) · Science · doi:10.1126/science.1153201 · Cited by 327 · see citing works
Whole Genome Deep Sequencing of HIV-1 Reveals the Impact of Early Minor Variants Upon Immune Recognition During Acute Infection
Henn, M. R., Boutwell, C. L., Charlebois, P., et al. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002529 · Cited by 321 · see citing works
All or nothing
Franks, P. W. (2000) · Cambridge University Press eBooks · doi:10.1017/ccol0521651786.006 · Cited by 320 · see citing works
Extensive editing of both hepatitis B virus DNA strands by APOBEC3 cytidine deaminases in vitro and in vivo
Suspène, R., Guétard, D., Henry, M., Sommer, P., Wain–Hobson, S., & Vartanian, J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408223102 · Cited by 305 · see citing works
Understanding HIV-1 latency provides clues for the eradication of long-term reservoirs
Coiras, M., López‐Huertas, M. R., Pérez‐Olmeda, M., & Alcamı́, J. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2223 · Cited by 281 · see citing works
MOSAIK: A Hash-Based Algorithm for Accurate Next-Generation Sequencing Short-Read Mapping
Lee, W.-P., Strömberg, M. P., Ward, A. N., Stewart, C., Garrison, E. P., & Marth, G. (2014) · PLoS ONE · doi:10.1371/journal.pone.0090581 · Cited by 281 · see citing works
Engineering attenuated virus vaccines by controlling replication fidelity
Vignuzzi, M., Wendt, E., & Andino, R. (2008) · Nature Medicine · doi:10.1038/nm1726 · Cited by 281 · see citing works
Extremely High Mutation Rate of a Hammerhead Viroid
Gago, S., Elena, S. F., Flores, R., & Sanjuán, R. (2009) · Science · doi:10.1126/science.1169202 · Cited by 266 · see citing works
Nature, Position, and Frequency of Mutations Made in a Single Cycle of HIV-1 Replication
Abram, M. E., Ferris, A. L., Shao, W., Alvord, W. G., & Hughes, S. H. (2010) · Journal of Virology · doi:10.1128/jvi.00915-10 · Cited by 264 · see citing works
Long-Term Transmission of Defective RNA Viruses in Humans and Aedes Mosquitoes
Aaskov, J., Buzacott, K., Thu, H. M., Lowry, K., & Holmes, E. C. (2006) · Science · doi:10.1126/science.1115030 · Cited by 260 · see citing works
Arbovirus high fidelity variant loses fitness in mosquitoes and mice
Coffey, L. L., Beeharry, Y., Bordería, A. V., Blanc, H., & Vignuzzi, M. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1111650108 · Cited by 249 · see citing works
Virulence and Pathogenesis of HIV-1 Infection: An Evolutionary Perspective
Fraser, C., Lythgoe, K., Leventhal, G. E., Shirreff, G., Hollingsworth, T. D., Alizon, S., & Bonhoeffer, S. (2014) · Science · doi:10.1126/science.1243727 · Cited by 236 · see citing works
De novo assembly of highly diverse viral populations
Yang, X. Q., Charlebois, P., Gnerre, S., Coole, M. G., Lennon, N. J., Levin, J. Z., Qu, J., Ryan, E. M., Zody, M. C., & Henn, M. R. (2012) · BMC Genomics · doi:10.1186/1471-2164-13-475 · Cited by 210 · see citing works
Fidelity of HIV-1 reverse transcriptase copying RNA in vitro
Ji, J., & Loeb, L. A. (1992) · Biochemistry · doi:10.1021/bi00119a002 · Cited by 208 · see citing works
Multiple APOBEC3 Restriction Factors for HIV-1 and One Vif to Rule Them All
Desimmie, B. A., Delviks‐Frankenberry, K. A., Burdick, R. C., Qi, D., Izumi, T., & Pathak, V. K. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.10.033 · Cited by 201 · see citing works
Extreme Genetic Fragility of the HIV-1 Capsid
Rihn, S. J., Wilson, S. J., Loman, N. J., Alim, M., Bakker, S. E., Bhella, D., Gifford, R. J., Rixon, F. J., & Bieniasz, P. D. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003461 · Cited by 190 · see citing works
APOBEC3G Contributes to HIV-1 Variation through Sublethal Mutagenesis
Sadler, H. A., Stenglein, M. D., Harris, R. S., & Mansky, L. M. (2010) · Journal of Virology · doi:10.1128/jvi.00056-10 · Cited by 174 · see citing works
G→A Hypermutation in Protease and Reverse Transcriptase Regions of Human Immunodeficiency Virus Type 1 Residing in Resting CD4 + T Cells In Vivo
Kieffer, T. L., Kwon, P., Nettles, R. E., Han, Y., Ray, S. C., & Siliciano, R. F. (2005) · Journal of Virology · doi:10.1128/jvi.79.3.1975-1980.2005 · Cited by 171 · see citing works
Identifying genetic markers of adaptation for surveillance of viral host jumps
Pepin, K. M., Lass, S., Pulliam, J. R. C., Read, A. F., & Lloyd‐Smith, J. O. (2010) · Nature Reviews Microbiology · doi:10.1038/nrmicro2440 · Cited by 167 · see citing works
Dynamics of Total, Linear Nonintegrated, and Integrated HIV‐1 DNA In Vivo and In Vitro
Koelsch, K. K., Liu, L., Haubrich, R., May, S. J., Havlir, D. V., Günthard, H. F., Ignacio, C. C., Campos‐Soto, P., Little, S. J., Shafer, R. W., et al. (2008) · The Journal of Infectious Diseases · doi:10.1086/525283 · Cited by 162 · see citing works
The origin of genetic diversity in HIV-1
Smyth, R. P., Davenport, M. P., & Mak, J. (2012) · Virus Research · doi:10.1016/j.virusres.2012.06.015 · Cited by 153 · see citing works
The Spanish HIV BioBank: a model of cooperative HIV research
García-Merino, I., Cuevas, N. D. L., Jiménez, J. L., et al. (2009) · Retrovirology · doi:10.1186/1742-4690-6-27 · Cited by 153 · see citing works
Effect of Ribavirin on the Mutation Rate and Spectrum of Hepatitis C Virus In Vivo
Cuevas, J. M., Gónzález‐Candelas, F., Moyá, A., & Sanjuán, R. (2009) · Journal of Virology · doi:10.1128/jvi.00201-09 · Cited by 150 · see citing works
Self-citation
Quantifying the Diversification of Hepatitis C Virus (HCV) during Primary Infection: Estimates of the In Vivo Mutation Rate
Ribeiro, R. M., Li, H., Wang, S., Stoddard, M. B., Learn, G. H., Korber, B., Tanmoy Bhattacharya, A., Guedj, J., Parrish, E. H., Hahn, B. H., et al. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002881 · Cited by 149 · see citing works
Genetic Editing of Herpes Simplex Virus 1 and Epstein-Barr Herpesvirus Genomes by Human APOBEC3 Cytidine Deaminases in Culture and In Vivo
Suspène, R., Aynaud, M.-M., Koch, S., Pasdeloup, D., Labétoulle, M., Gaertner, B., Vartanian, J., Meyerhans, A., & Wain–Hobson, S. (2011) · Journal of Virology · doi:10.1128/jvi.00290-11 · Cited by 142 · see citing works
T-Cell Vaccine Strategies for Human Immunodeficiency Virus, the Virus with a Thousand Faces
Korber, B., Letvin, N. L., & Haynes, B. F. (2009) · Journal of Virology · doi:10.1128/jvi.00114-09 · Cited by 142 · see citing works
Measurement and modeling of human T cell kinetics
Macallan, D. C., Asquith, B., Irvine, A. J., Wallace, D. L., Worth, A. T., Ghattas, H., Zhang, Y., Griffin, G. E., Tough, D. F., & Beverley, P. C. L. (2003) · European Journal of Immunology · doi:10.1002/eji.200323763 · Cited by 129 · see citing works
Retrovirus mutation rates and their role in genetic variation.
Mansky, L. M. (1998) · Journal of General Virology · doi:10.1099/0022-1317-79-6-1337 · Cited by 118 · see citing works
Analysis of Human APOBEC3H Haplotypes and Anti-Human Immunodeficiency Virus Type 1 Activity
Wang, X., Abudu, A., Son, S., Dang, Y., Venta, P. J., & Zheng, Y. (2011) · Journal of Virology · doi:10.1128/jvi.02049-10 · Cited by 111 · see citing works
Mutation Rates and Intrinsic Fidelity of Retroviral Reverse Transcriptases
Menéndez‐Arias, L. (2009) · Viruses · doi:10.3390/v1031137 · Cited by 111 · see citing works
The Activity Spectrum of Vif from Multiple HIV-1 Subtypes against APOBEC3G, APOBEC3F, and APOBEC3H
Binka, M., Ooms, M., Steward, M., et al. (2011) · Journal of Virology · doi:10.1128/jvi.06082-11 · Cited by 106 · see citing works
Natural Polymorphisms in Human APOBEC3H and HIV-1 Vif Combine in Primary T Lymphocytes to Affect Viral G-to-A Mutation Levels and Infectivity
Refsland, E. W., Hultquist, J. F., Luengas, E. M., Ikeda, T., Shaban, N. M., Law, E. K., Brown, W. L., Reilly, C., Emerman, M., & Harris, R. S. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004761 · Cited by 103 · see citing works
HIV-1 Vif Adaptation to Human APOBEC3H Haplotypes
Ooms, M., Brayton, B., Letko, M. C., Maio, S. M., Pilcher, C. D., Hecht, F. M., Barbour, J. D., & Simon, V. R. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.09.006 · Cited by 102 · see citing works
RNA Virus Population Diversity, an Optimum for Maximal Fitness and Virulence
Korboukh, V. K., Lee, C. A., Acevedo, A., Vignuzzi, M., Xiao, Y., Arnold, J. J., Hemperly, S., Graci, J. D., August, A., Andino, R., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.592303 · Cited by 96 · see citing works
Attenuation of Human Enterovirus 71 High-Replication-Fidelity Variants in AG129 Mice
Meng, T., & Kwang, J. (2014) · Journal of Virology · doi:10.1128/jvi.00289-14 · Cited by 90 · see citing works
Conserved Footprints of APOBEC3G on Hypermutated Human Immunodeficiency Virus Type 1 and Human Endogenous Retrovirus HERV-K(HML2) Sequences
Armitage, A. E., Katzourakis, A., de Oliveira, T., Welch, J. J., Belshaw, R. D., Bishop, K. N., Kramer, B., McMichael, A. J., Rambaut, A., & Iversen, A. K. N. (2008) · Journal of Virology · doi:10.1128/jvi.00584-08 · Cited by 87 · see citing works
HIV tropism: diagnostic tools and implications for disease progression and treatment with entry inhibitors
Poveda, E., Briz, V., Quiñones‐Mateu, M. E., & Soriano, V. (2006) · AIDS · doi:10.1097/01.aids.0000233569.74769.69 · Cited by 87 · see citing works
Deoxyribonucleoside Triphosphate Pool Imbalances In Vivo Are Associated with an Increased Retroviral Mutation Rate
Julias, J. G., & Pathak, V. K. (1998) · Journal of Virology · doi:10.1128/jvi.72.10.7941-7949.1998 · Cited by 86 · see citing works
AID and APOBECs span the gap between innate and adaptive immunity
Moris, A., Murray, S. M., & Cardinaud, S. (2014) · Frontiers in Microbiology · doi:10.3389/fmicb.2014.00534 · Cited by 79 · see citing works
APOBEC3G-Induced Hypermutation of Human Immunodeficiency Virus Type-1 Is Typically a Discrete “All or Nothing” Phenomenon
Armitage, A. E., Deforche, K., Chang, C., Wee, E. G., Kramer, B., Welch, J. J., Gerstoft, J., Fugger, L. H., McMichael, A. J., Rambaut, A., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002550 · Cited by 76 · see citing works
APOBEC3G induces a hypermutation gradient: purifying selection at multiple steps during HIV-1 replication results in levels of G-to-A mutations that are high in DNA, intermediate in cellular viral RNA, and low in virion RNA
Russell, R. A., Moore, M. D., Hu, W.-S., & Pathak, V. K. (2009) · Retrovirology · doi:10.1186/1742-4690-6-16 · Cited by 76 · see citing works
Analysis of the Percentage of Human Immunodeficiency Virus Type 1 Sequences That Are Hypermutated and Markers of Disease Progression in a Longitudinal Cohort, Including One Individual with a Partially Defective Vif
Piantadosi, A. L., Humes, D. G., Chohan, B. H., McClelland, R. S., & Overbaugh, J. M. (2009) · Journal of Virology · doi:10.1128/jvi.00280-09 · Cited by 73 · see citing works
Influence of Reverse Transcriptase Variants, Drugs, and Vpr on Human Immunodeficiency Virus Type 1 Mutant Frequencies
Mansky, L. M., Rouzic, E. L., Bénichou, S., & Gajary, L. C. (2003) · Journal of Virology · doi:10.1128/jvi.77.3.2071-2080.2003 · Cited by 72 · see citing works
A-to-G Hypermutation in the Genome of Lymphocytic Choriomeningitis Virus
Zahn, R. C., Schelp, I., Utermöhlen, O., & von Laer, D. (2006) · Journal of Virology · doi:10.1128/jvi.00067-06 · Cited by 71 · see citing works
Correlation Between Mutation Rate and Genome Size in Riboviruses: Mutation Rate of Bacteriophage Qβ
Bradwell, K. R., Combe, M., Domingo‐Calap, P., & Sanjuán, R. (2013) · Genetics · doi:10.1534/genetics.113.154963 · Cited by 71 · see citing works
Self-citation
Single-molecule PCR: an artifact-free PCR approach for the analysis of somatic mutations
Kraytsberg, Y., & Khrapko, K. (2005) · Expert Review of Molecular Diagnostics · doi:10.1586/14737159.5.5.809 · Cited by 68 · see citing works
Integrated HIV DNA accumulates prior to treatment while episomal HIV DNA records ongoing transmission afterwards
Murray, J. M., McBride, K. L., Boesecke, C., Bailey, M., Amin, J., Suzuki, K., Baker, D., Zaunders, J. J., Emery, S., Cooper, D. A., et al. (2012) · AIDS · doi:10.1097/qad.0b013e328350fb3c · Cited by 66 · see citing works
Numerous transitions in human parainfluenza virus 3 RNA recovered from persistently infected cells
Murphy, D. G., Dimock, K., & Kang, C. Y. (1991) · Virology · doi:10.1016/0042-6822(91)90913-v · Cited by 64 · see citing works
Host Factors and HIV-1 Replication: Clinical Evidence and Potential Therapeutic Approaches
Santa‐Marta, M., de Brito, P. M., Godinho‐Santos, A., & Gonçalves, J. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00343 · Cited by 61 · see citing works
End-point limiting-dilution real-time PCR assay for evaluation of hepatitis C virus quasispecies in serum: Performance under optimal and suboptimal conditions
Ramachandran, S., Xia, G.-L., Ganova-Raeva, L. M., et al. (2008) · Journal of Virological Methods · doi:10.1016/j.jviromet.2008.05.005 · Cited by 61 · see citing works
Rates of HIV immune escape and reversion: implications for vaccination
Davenport, M. P., Loh, L., Petravic, J., et al. (2008) · Trends in Microbiology · doi:10.1016/j.tim.2008.09.001 · Cited by 60 · see citing works
Variable contexts and levels of hypermutation in HIV-1 proviral genomes recovered from primary peripheral blood mononuclear cells
Kijak, G. H., Janini, L. M., Tovanabutra, S., et al. (2008) · Virology · doi:10.1016/j.virol.2008.03.017 · Cited by 55 · see citing works
Relationship Between HIV Coreceptor Tropism and Disease Progression in Persons With Untreated Chronic HIV Infection
Goetz, M. B., Leduc, R. E., Kostman, J. R., et al. (2009) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0b013e3181989a8b · Cited by 55 · see citing works
E138K and M184I mutations in HIV-1 reverse transcriptase coemerge as a result of APOBEC3 editing in the absence of drug exposure
Fourati, S., Malet, I., Lambert-Niclot, S., et al. (2012) · AIDS · doi:10.1097/qad.0b013e3283560703 · Cited by 52 · see citing works
Positioning of APOBEC3G/F Mutational Hotspots in the Human Immunodeficiency Virus Genome Favors Reduced Recognition by CD8+ T Cells
Monajemi, M., Woodworth, C. F., Zipperlen, K., Gallant, M., Grant, M. D., & Larijani, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093428 · Cited by 46 · see citing works
The Level of APOBEC3G (hA3G)-Related G-to-A Mutations Does Not Correlate with Viral Load in HIV Type 1-Infected Individuals
Ulenga, N. K., Sarr, A. D., Hamel, D. J., Sankalé, J.-L., Mboup, S., & Kanki, P. J. (2008) · AIDS Research and Human Retroviruses · doi:10.1089/aid.2008.0072 · Cited by 45 · see citing works
Inversing the natural hydrogen bonding rule to selectively amplify GC-rich ADAR-edited RNAs
Suspène, R., Renard, M., Henry, M., Guétard, D., Zemmour, D., Billecocq, A., Bouloy, M., Tangy, F., Vartanian, J., & Wain–Hobson, S. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn295 · Cited by 43 · see citing works
A model for the generation of multiple A to G transitions in the human respiratory syncytial virus genome: predicted RNA secondary structures as substrates for adenosine deaminases that act on RNA
Martínez, I., & Melero, J. A. (2002) · Journal of General Virology · doi:10.1099/0022-1317-83-6-1445 · Cited by 42 · see citing works
APOBEC3G expression and hypermutation are inversely associated with human immunodeficiency virus type 1 (HIV-1) burden in vivo
Kourteva, Y., Pasquale, M. P. D., Allos, T. M., McMunn, C., & D’Aquila, R. T. (2012) · Virology · doi:10.1016/j.virol.2012.03.018 · Cited by 39 · see citing works
Elevated hypermutation levels in HIV-1 natural viral suppressors
Eyzaguirre, L. M., Charurat, M., Redfield, R., et al. (2013) · Virology · doi:10.1016/j.virol.2013.05.019 · Cited by 34 · see citing works
A combination of defective DNA and protective host factors are found in a set of HIV-1 ancestral LTNPs
Sandonís, V., Casado, C., Alvaro, T., Pernas, M., Olivares, I., García, S., Rodríguez, C., del Romero, J., & López‐Galíndez, C. (2009) · Virology · doi:10.1016/j.virol.2009.05.022 · Cited by 30 · see citing works
Variation of HIV-1 Mutation Spectra among Cell Types
Holtz, C. M., & Mansky, L. M. (2013) · Journal of Virology · doi:10.1128/jvi.03576-12 · Cited by 30 · see citing works
Expression of APOBEC3G/3F and G-to-A Hypermutation Levels in HIV-1-Infected Children with Different Profiles of Disease Progression
Amoêdo, N. D., Afonso, A. O., Cunha, S. M., de Oliveira, R. H., Machado, E. S., & Soares, M. A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024118 · Cited by 23 · see citing works
Uneven Genetic Robustness of HIV-1 Integrase
Rihn, S. J., Hughes, J., Wilson, S. J., & Bieniasz, P. D. (2014) · Journal of Virology · doi:10.1128/jvi.02451-14 · Cited by 20 · see citing works
Requirement of HIV-1 Vif C-terminus for Vif-CBF-β interaction and assembly of CUL5-containing E3 ligase
Wang, H., Lv, G., Zhou, X., Li, Z., Liu, X., Yu, X.-F., & Zhang, W. (2014) · BMC Microbiology · doi:10.1186/s12866-014-0290-7 · Cited by 13 · see citing works

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mRNA vaccines for infectious diseases: principles, delivery and clinical translation
Chaudhary, N., Weissman, D., & Whitehead, K. A. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00283-5 · Cited by 1,555 · see citing works
Transcriptome-wide Cas13 guide RNA design for model organisms and viral RNA pathogens
Guo, X., Rahman, J. A., Wessels, H.-H., Méndez-Mancilla, A., Haro, D., Chen, X., & Sanjana, N. E. (2021) · Cell Genomics · doi:10.1016/j.xgen.2021.100001 · Cited by 79 · see citing works

Authors: Cuevas, J. M., Geller, R., Garijo, R., López-Aldeguer, J., & Sanjuán, R.
Affiliations: Universitat de València (ES)
Corresponding author: Sanjuán, Rafael
ORCID: Cuevas, José M.
Geller, Ron
Sanjuán, Rafael
Venue: PLOS Biology
Publisher: Public Library of Science (PLoS)
Published: 2015-09-16
Volume: 13
Issue: 9
Pages: e1002251
ISSN: 1544-9173 (ISSN-L)
1545-7885
DOI: 10.1371/journal.pbio.1002251
PMC: PMC4574155
OpenAlex: W2198318089
Cited by: 371
References: 83
Citations by year: 2026: 17 · 2025: 33 · 2024: 25 · 2023: 29 · 2022: 48 · 2021: 49 · 2020: 47 · 2019: 37 · 2018: 21 · 2017: 34 · 2016: 29 · 2015: 2
FWCI: 14.50
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: PLoS Biology (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DIGITAL.CSIC (Spanish National Research Council (CSIC)) (acceptedVersion, other-oa)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Figshare (submittedVersion, cc-by)
Funders: Instituto de Salud Carlos III (RD12/0017)
FP7 Ideas: European Research Council (281191)
Topics: Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords: HIV-1, spontaneous mutation rate, premature stop codon, APOBEC3A, APOBEC3B, cytidine deaminase, reverse transcriptase, antiviral defense, viral genetic diversity, disease progression, peripheral blood mononuclear cells, RNA virus evolution
MeSH terms: Adult, Female, Humans, Male, Middle Aged, HIV-1, HIV Infections, Sequence Analysis, RNA, Disease Progression, Young Adult, Mutation Rate

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Extremely High Mutation Rate of HIV-1 In Vivo

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