Tracking HIV-1 recombination to resolve its contribution to HIV-1 evolution in natural infection

Song, Hongshuo; Giorgi, Elena Edi; Ganusov, Vitaly V.; Cai, Fangping; Athreya, Gayathri; Yoon, Hyejin; Carja, Oana; Hora, Bhavna; Hraber, Peter Thomas; Romero-Severson, Ethan; Jiang, Chunlai; Li, Xiaojun; Wang, Shuyi; Li, Hui; Salazar-Gonzalez, Jesus F.; Salazar, Maria G.; Goonetilleke, Nilu; Keele, Brandon F.; Montefiori, David C.; Cohen, Myron S.; Shaw, George M.; Hahn, Beatrice H.; McMichael, Andrew J.; Haynes, Barton F.; Korber, Bette Tina Marie; Bhattacharya, Tanmoy; Gao, Feng

doi:10.1038/s41467-018-04217-5

Title: Tracking HIV-1 recombination to resolve its contribution to HIV-1 evolution in natural infection

Journal Article · Tue May 15 00:00:00 EDT 2018 · Nature Communications

DOI:https://doi.org/10.1038/s41467-018-04217-5· OSTI ID:1593118

Song, Hongshuo ^[1];

^[2]; Ganusov, Vitaly V. ^[3]; Cai, Fangping ^[4]; Athreya, Gayathri ^[5]; Yoon, Hyejin ^[2]; Carja, Oana ^[6]; Hora, Bhavna ^[4];

^[2];

^[2]; Jiang, Chunlai ^[7]; Li, Xiaojun ^[4]; Wang, Shuyi ^[6]; Li, Hui ^[6]; Salazar-Gonzalez, Jesus F. ^[8]; Salazar, Maria G. ^[9]; Goonetilleke, Nilu ^[10]; Keele, Brandon F. ^[11]; Montefiori, David C. ^[4]; Cohen, Myron S. ^[10] more »

Duke Univ. Medical Center, Durham, NC (United States); Walter Reed Army Institute of Research, Silver Spring, MD (United States)
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Univ. of Tennessee, Knoxville, TN (United States)
Duke Univ. Medical Center, Durham, NC (United States)
Univ. of Arizona, Tucson, AZ (United States)
Univ. of Pennsylvania, Philadelphia, PA (United States)
Duke Univ. Medical Center, Durham, NC (United States); Jilin Univ. (China)
Univ. of Alabama, Birmingham, AL (United States); MRC/UVRI and LSHTM Uganda Research Unit, Entebbe (Uganda)
Univ. of Alabama, Birmingham, AL (United States)
Univ. of North Carolina, Chapel Hill, NC (United States)
Frederick National Laboratory for Cancer Research, Frederick, MD (United States)
Univ. of Oxford (United Kingdom)

Recombination in HIV-1 is well documented, but its importance in the low-diversity setting of within-host diversification is less understood. Here we develop a novel computational tool (RAPR (Recombination Analysis PRogram)) to enable a detailed view of in vivo viral recombination during early infection, and we apply it to near-full-length HIV-1 genome sequences from longitudinal samples. Recombinant genomes rapidly replace transmitted/founder (T/F) lineages, with a median half-time of 27 days, increasing the genetic complexity of the viral population. We identify recombination hot and cold spots that differ from those observed in inter-subtype recombinants. Furthermore, RAPR analysis of longitudinal samples from an individual with well-characterized neutralizing antibody responses shows that recombination helps carry forward resistance-conferring mutations in the diversifying quasispecies. These findings provide insight into molecular mechanisms by which viral recombination contributes to HIV-1 persistence and immunopathogenesis and have implications for studies of HIV transmission and evolution in vivo.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: USDOE Laboratory Directed Research and Development (LDRD) Program

Grant/Contract Number:: 89233218CNA000001; R01AI087520; AI100645; AAI 12007-0000-01000; HHSN261200800001E

OSTI ID:: 1593118

Report Number(s):: LA-UR-19-30217

Journal Information:: Nature Communications, Vol. 9, Issue 1; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

Citation Metrics:

Cited by: 51 works

Citation information provided by
Web of Science

References (60)

High-Frequency Illegitimate Strand Transfers of Nascent DNA Fragments During Reverse Transcription Result in Defective Retrovirus Genomes Li, Xiaojun; Fan, Peihu; Jiang, Chunlai JAIDS Journal of Acquired Immune Deficiency Syndromes, Vol. 72, Issue 4 https://doi.org/10.1097/QAI.0000000000000952	journal	January 2016
Recombination-mediated escape from primary CD8+ T cells in acute HIV-1 infection Ritchie, Adam John; Cai, Fangping; Smith, Nicola MG Retrovirology, Vol. 11, Issue 1 https://doi.org/10.1186/s12977-014-0069-9	journal	September 2014
Estimating the in-vivo HIV template switching and recombination rate Cromer, Deborah; Grimm, Andrew J.; Schlub, Timothy E. AIDS, Vol. 30, Issue 2 https://doi.org/10.1097/QAD.0000000000000936	journal	January 2016
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. Journal of Virology, Vol. 82, Issue 8 https://doi.org/10.1128/JVI.02660-07	journal	February 2008
Mathematical modeling of escape of HIV from cytotoxic T lymphocyte responses Ganusov, Vitaly V.; Neher, Richard A.; Perelson, Alan S. Journal of Statistical Mechanics: Theory and Experiment, Vol. 2013, Issue 01 https://doi.org/10.1088/1742-5468/2013/01/P01010	journal	January 2013
Human Immunodeficiency Virus Type 1 Genetic Recombination Is More Frequent Than That of Moloney Murine Leukemia Virus despite Similar Template Switching Rates Onafuwa, A.; An, W.; Robson, N. D. Journal of Virology, Vol. 77, Issue 8 https://doi.org/10.1128/JVI.77.8.4577-4587.2003	journal	April 2003
Properties of human immunodeficiency virus type 1 reverse transcriptase recombination upon infection Sakuragi, Jun-ichi; Sakuragi, Sayuri; Shioda, Tatsuo Journal of General Virology, Vol. 96, Issue 11 https://doi.org/10.1099/jgv.0.000265	journal	November 2015
Staged induction of HIV-1 glycan–dependent broadly neutralizing antibodies Bonsignori, Mattia; Kreider, Edward F.; Fera, Daniela Science Translational Medicine, Vol. 9, Issue 381 https://doi.org/10.1126/scitranslmed.aai7514	journal	March 2017
The role of recombination in the emergence of a complex and dynamic HIV epidemic Zhang, Ming; Foley, Brian; Schultz, Anne-Kathrin Retrovirology, Vol. 7, Issue 1 https://doi.org/10.1186/1742-4690-7-25	journal	March 2010
Immune-driven recombination and loss of control after HIV superinfection Streeck, Hendrik; Li, Bin; Poon, Art F. Y. The Journal of Experimental Medicine, Vol. 205, Issue 8 https://doi.org/10.1084/jem.20080281	journal	July 2008
Modeling sequence evolution in HIV-1 infection with recombination Giorgi, Elena E.; Korber, Bette T.; Perelson, Alan S. Journal of Theoretical Biology, Vol. 329 https://doi.org/10.1016/j.jtbi.2013.03.026	journal	July 2013
Recombination-Mediated Changes in Coreceptor Usage Confer an Augmented Pathogenic Phenotype in a Nonhuman Primate Model of HIV-1-Induced AIDS Nishimura, Y.; Shingai, M.; Lee, W. R. Journal of Virology, Vol. 85, Issue 20 https://doi.org/10.1128/JVI.05010-11	journal	August 2011
Comments on the detection of reciprocal recombination or gene conversion Takahata, Naoyuki Immunogenetics, Vol. 39, Issue 2 https://doi.org/10.1007/BF00188618	journal	January 1994
An Evolutionary Model-Based Algorithm for Accurate Phylogenetic Breakpoint Mapping and Subtype Prediction in HIV-1 Kosakovsky Pond, Sergei L.; Posada, David; Stawiski, Eric PLoS Computational Biology, Vol. 5, Issue 11 https://doi.org/10.1371/journal.pcbi.1000581	journal	November 2009
Recombination Rate and Selection Strength in HIV Intra-patient Evolution Neher, Richard A.; Leitner, Thomas PLoS Computational Biology, Vol. 6, Issue 1 https://doi.org/10.1371/journal.pcbi.1000660	journal	January 2010
Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection Salazar-Gonzalez, Jesus F.; Salazar, Maria G.; Keele, Brandon F. The Journal of Experimental Medicine, Vol. 206, Issue 6 https://doi.org/10.1084/jem.20090378	journal	June 2009
HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time Perelson, A. S.; Neumann, A. U.; Markowitz, M. Science, Vol. 271, Issue 5255 https://doi.org/10.1126/science.271.5255.1582	journal	March 1996
Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques Santra, Sampa; Tomaras, Georgia D.; Warrier, Ranjit PLOS Pathogens, Vol. 11, Issue 8 https://doi.org/10.1371/journal.ppat.1005042	journal	August 2015
Recco: recombination analysis using cost optimization Maydt, Jochen; Lengauer, Thomas Bioinformatics, Vol. 22, Issue 9 https://doi.org/10.1093/bioinformatics/btl057	journal	February 2006
Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus Liao, Hua-Xin; Lynch, Rebecca; Zhou, Tongqing Nature, Vol. 496, Issue 7446 https://doi.org/10.1038/nature12053	journal	April 2013
Recommendations for enterovirus diagnostics and characterisation within and beyond Europe Harvala, Heli; Broberg, Eeva; Benschop, Kimberley Journal of Clinical Virology, Vol. 101 https://doi.org/10.1016/j.jcv.2018.01.008	journal	April 2018
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. Proceedings of the National Academy of Sciences, Vol. 105, Issue 21 https://doi.org/10.1073/pnas.0802203105	journal	May 2008
Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody Bonsignori, Mattia; Zhou, Tongqing; Sheng, Zizhang Cell, Vol. 165, Issue 2 https://doi.org/10.1016/j.cell.2016.02.022	journal	April 2016
Application of Phylogenetic Networks in Evolutionary Studies Huson, Daniel H.; Bryant, David Molecular Biology and Evolution, Vol. 23, Issue 2 https://doi.org/10.1093/molbev/msj030	journal	October 2005
Rapid production and clearance of HIV-1 and hepatitis C virus assessed by large volume plasma apheresis Ramratnam, Bharat; Bonhoeffer, Sebastian; Binley, James The Lancet, Vol. 354, Issue 9192 https://doi.org/10.1016/S0140-6736(99)02035-8	journal	November 1999
Approximate Bayesian Computation Sunnåker, Mikael; Busetto, Alberto Giovanni; Numminen, Elina PLoS Computational Biology, Vol. 9, Issue 1 https://doi.org/10.1371/journal.pcbi.1002803	journal	January 2013
Transmission of Multiple HIV-1 Subtype C Transmitted/founder Viruses into the Same Recipients Was not Determined by Modest Phenotypic Differences Song, Hongshuo; Hora, Bhavna; Giorgi, Elena E. Scientific Reports, Vol. 6, Issue 1 https://doi.org/10.1038/srep38130	journal	December 2016
Why do RNA viruses recombine? Simon-Loriere, Etienne; Holmes, Edward C. Nature Reviews Microbiology, Vol. 9, Issue 8 https://doi.org/10.1038/nrmicro2614	journal	July 2011
Pervasive Genomic Recombination of HIV-1 in Vivo Shriner, Daniel; Rodrigo, Allen G.; Nickle, David C. Genetics, Vol. 167, Issue 4 https://doi.org/10.1534/genetics.103.023382	journal	August 2004
Identifying the Important HIV-1 Recombination Breakpoints Archer, John; Pinney, John W.; Fan, Jun PLoS Computational Biology, Vol. 4, Issue 9 https://doi.org/10.1371/journal.pcbi.1000178	journal	September 2008
Contribution of Recombination to the Evolution of Human Immunodeficiency Viruses Expressing Resistance to Antiretroviral Treatment Nora, T.; Charpentier, C.; Tenaillon, O. Journal of Virology, Vol. 81, Issue 14 https://doi.org/10.1128/JVI.00083-07	journal	May 2007
Detecting hypermutations in viral sequences with an emphasis on G -> A hypermutation Rose, P. P.; Korber, B. T. Bioinformatics, Vol. 16, Issue 4 https://doi.org/10.1093/bioinformatics/16.4.400	journal	April 2000
Cooperation of B Cell Lineages in Induction of HIV-1-Broadly Neutralizing Antibodies Gao, Feng; Bonsignori, Mattia; Liao, Hua-Xin Cell, Vol. 158, Issue 3 https://doi.org/10.1016/j.cell.2014.06.022	journal	July 2014
Multiple Pathways of Escape from HIV Broadly Cross-Neutralizing V2-Dependent Antibodies Moore, P. L.; Sheward, D.; Nonyane, M. Journal of Virology, Vol. 87, Issue 9 https://doi.org/10.1128/JVI.03424-12	journal	February 2013
Human Immunodeficiency Virus Type 1 Recombination: Rate, Fidelity, and Putative Hot Spots Zhuang, J.; Jetzt, A. E.; Sun, G. Journal of Virology, Vol. 76, Issue 22 https://doi.org/10.1128/JVI.76.22.11273-11282.2002	journal	November 2002
Broadly neutralizing antibodies with few somatic mutations and hepatitis C virus clearance Bailey, Justin R.; Flyak, Andrew I.; Cohen, Valerie J. JCI Insight, Vol. 2, Issue 9 https://doi.org/10.1172/jci.insight.92872	journal	May 2017
Modelling viral and immune system dynamics Perelson, Alan S. Nature Reviews Immunology, Vol. 2, Issue 1 https://doi.org/10.1038/nri700	journal	January 2002
Intercompartmental Recombination of HIV-1 Contributes to env Intrahost Diversity and Modulates Viral Tropism and Sensitivity to Entry Inhibitors Brown, R. J. P.; Peters, P. J.; Caron, C. Journal of Virology, Vol. 85, Issue 12 https://doi.org/10.1128/JVI.00131-11	journal	April 2011
The Effect of Recombination on the Accuracy of Phylogeny Estimation Posada, David; Crandall, Keith A. Journal of Molecular Evolution, Vol. 54, Issue 3 https://doi.org/10.1007/s00239-001-0034-9	journal	March 2002
Estimate of effective recombination rate and average selection coefficient for HIV in chronic infection Batorsky, R.; Kearney, M. F.; Palmer, S. E. Proceedings of the National Academy of Sciences, Vol. 108, Issue 14 https://doi.org/10.1073/pnas.1102036108	journal	March 2011
Molecular surveillance of norovirus, 2005–16: an epidemiological analysis of data collected from the NoroNet network van Beek, Janko; de Graaf, Miranda; Al-Hello, Haider The Lancet Infectious Diseases, Vol. 18, Issue 5 https://doi.org/10.1016/S1473-3099(18)30059-8	journal	May 2018
Analysis of HIV-1 intersubtype recombination breakpoints suggests region with high pairing probability may be a more fundamental factor than sequence similarity affecting HIV-1 recombination Jia, Lei; Li, Lin; Gui, Tao Virology Journal, Vol. 13, Issue 1 https://doi.org/10.1186/s12985-016-0616-1	journal	September 2016
Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection Fiebig, Eberhard W.; Wright, David J.; Rawal, Bhupat D. AIDS, Vol. 17, Issue 13 https://doi.org/10.1097/00002030-200309050-00005	journal	January 2003
A Computer Program Designed to Screen Rapidly for HIV Type 1 Intersubtype Recombinant Sequences Siepel, Adam C.; Halpern, Aaron L.; Macken, Catherine AIDS Research and Human Retroviruses, Vol. 11, Issue 11 https://doi.org/10.1089/aid.1995.11.1413	journal	November 1995
Recombination leads to the rapid emergence of HIV-1 dually resistant mutants under selective drug pressure. Moutouh, L.; Corbeil, J.; Richman, D. D. Proceedings of the National Academy of Sciences, Vol. 93, Issue 12 https://doi.org/10.1073/pnas.93.12.6106	journal	June 1996
Estimating time since infection in early homogeneous HIV-1 samples using a poisson model Giorgi, Elena E.; Funkhouser, Bob; Athreya, Gayathri BMC Bioinformatics, Vol. 11, Issue 1 https://doi.org/10.1186/1471-2105-11-532	journal	October 2010
Sequence determinants of breakpoint location during HIV-1 intersubtype recombination Baird, Heather A.; Galetto, Román; Gao, Yong Nucleic Acids Research, Vol. 34, Issue 18 https://doi.org/10.1093/nar/gkl669	journal	September 2006
Clinical, virologic, and immunologic correlates of HIV-1 intraclade B dual infection among men who have sex with men Pacold, Mary E.; Pond, Sergei L. Kosakovsky; Wagner, Gabriel A. AIDS, Vol. 26, Issue 2 https://doi.org/10.1097/QAD.0b013e32834dcd26	journal	January 2012
Selection for Human Immunodeficiency Virus Type 1 Recombinants in a Patient with Rapid Progression to AIDS Liu, S. -L.; Mittler, J. E.; Nickle, D. C. Journal of Virology, Vol. 76, Issue 21 https://doi.org/10.1128/JVI.76.21.10674-10684.2002	journal	November 2002
Molecular characterization of hepatitis B virus in Bangladesh reveals a highly recombinant population Munshi, Saif Ullah; Tran, Thanh Thi Thanh; Vo, Truc Nhu Thanh PLOS ONE, Vol. 12, Issue 12 https://doi.org/10.1371/journal.pone.0188944	journal	December 2017
APE: Analyses of Phylogenetics and Evolution in R language Paradis, E.; Claude, J.; Strimmer, K. Bioinformatics, Vol. 20, Issue 2 https://doi.org/10.1093/bioinformatics/btg412	journal	January 2004
Recombination Analysis Tool (RAT): a program for the high-throughput detection of recombination Etherington, G. J.; Dicks, J.; Roberts, I. N. Bioinformatics, Vol. 21, Issue 3 https://doi.org/10.1093/bioinformatics/bth500	journal	August 2004
Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies Doria-Rose, Nicole A.; Schramm, Chaim A.; Gorman, Jason Nature, Vol. 509, Issue 7498 https://doi.org/10.1038/nature13036	journal	March 2014
Mechanisms and Factors that Influence High Frequency Retroviral Recombination Delviks-Frankenberry, Krista; Galli, Andrea; Nikolaitchik, Olga Viruses, Vol. 3, Issue 9 https://doi.org/10.3390/v3091650	journal	September 2011
Extensive Recombination among Human Immunodeficiency Virus Type 1 Quasispecies Makes an Important Contribution to Viral Diversity in Individual Patients Charpentier, C.; Nora, T.; Tenaillon, O. Journal of Virology, Vol. 80, Issue 5 https://doi.org/10.1128/JVI.80.5.2472-2482.2006	journal	February 2006
Unselected Mutations in the Human Immunodeficiency Virus Type 1 Genome Are Mostly Nonsynonymous and Often Deleterious Gao, F.; Chen, Y.; Levy, D. N. Journal of Virology, Vol. 78, Issue 5 https://doi.org/10.1128/JVI.78.5.2426-2433.2004	journal	February 2004
RDP4: Detection and analysis of recombination patterns in virus genomes Martin, Darren P.; Murrell, Ben; Golden, Michael Virus Evolution, Vol. 1, Issue 1 https://doi.org/10.1093/ve/vev003	journal	March 2015
Evaluation of methods for detecting recombination from DNA sequences: Computer simulations Posada, D.; Crandall, K. A. Proceedings of the National Academy of Sciences, Vol. 98, Issue 24 https://doi.org/10.1073/pnas.241370698	journal	November 2001
MEGA6: Molecular Evolutionary Genetics Analysis Version 6.0 Tamura, Koichiro; Stecher, Glen; Peterson, Daniel Molecular Biology and Evolution, Vol. 30, Issue 12 https://doi.org/10.1093/molbev/mst197	journal	October 2013
Accurately Measuring Recombination between Closely Related HIV-1 Genomes Schlub, Timothy E.; Smyth, Redmond P.; Grimm, Andrew J. PLoS Computational Biology, Vol. 6, Issue 4 https://doi.org/10.1371/journal.pcbi.1000766	journal	April 2010

Cited By (2)

Modular nature of simian foamy virus genomes and their evolutionary history Aiewsakun, Pakorn; Richard, Léa; Gessain, Antoine Virus Evolution, Vol. 5, Issue 2 https://doi.org/10.1093/ve/vez032	journal	July 2019
Combining Viral Genetics and Statistical Modeling to Improve HIV-1 Time-of-Infection Estimation towards Enhanced Vaccine Efficacy Assessment Rossenkhan, Raabya; Rolland, Morgane; Labuschagne, Jan Viruses, Vol. 11, Issue 7 https://doi.org/10.3390/v11070607	journal	July 2019

Similar Records

Low dose rectal inoculation of rhesus macaques by SIV SME660 or SIV MAC251 recapitulates human mucosal infection by HIV-1

Journal Article · Thu Jan 01 00:00:00 EST 2009 · Journal of Experimental Medicine · OSTI ID:1593118

Koraber, Bette; Perelson, Alan; Hraber, Peter; +2 more

Recombination enhances HIV-1 envelope diversity by facilitating the survival of latent genomic fragments in the plasma virus population

Journal Article · Tue Dec 22 00:00:00 EST 2015 · PLoS Computational Biology (Online) · OSTI ID:1593118

Immonen, Taina T.; Conway, Jessica M.; Romero-Severson, Ethan O.; +3 more

High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men

Journal Article · Thu May 13 00:00:00 EDT 2010 · PLoS Pathogens · OSTI ID:1593118

Li, Hui; Bar, Katharine J.; Wang, Shuyi; +21 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Biological Science

Title: Tracking HIV-1 recombination to resolve its contribution to HIV-1 evolution in natural infection

Citation Formats

References (60)

Cited By (2)

Similar Records

Related Subjects