1887

Abstract

Human immunodeficiency virus intra-host recombination has never been studied both during early infection and throughout disease progression. The CD8-depleted rhesus macaque model of neuroAIDS was used to investigate the impact of recombination from early infection up to the onset of neuropathology in animals inoculated with a simian immunodeficiency virus (SIV) swarm. Several lymphoid and non-lymphoid tissues were collected longitudinally at 21 days post-infection (p.i.), 61 days p.i. and necropsy (75–118 days p.i.) from four macaques that developed SIV-encephalitis or meningitis, as well as from two animals euthanized at 21 days p.i. The number of recombinant sequences and breakpoints in different tissues and over time from each primate were compared. Breakpoint locations were mapped onto predicted RNA and protein secondary structures. Recombinants were found at each time point and in each primate as early as 21 days p.i. No association was found between recombination rates and specific tissue of origin. Several identical breakpoints were identified in sequences derived from different tissues in the same primate and among different primates. Breakpoints predominantly mapped to unpaired nucleotides or pseudoknots in RNA secondary structures, and proximal to glycosylation sites and cysteine residues in protein sequences, suggesting selective advantage in the emergence of specific recombinant sequences. Results indicate that recombinant sequences can become fixed very early after infection with a heterogeneous viral swarm. Features of RNA and protein secondary structure appear to play a role in driving the production of recombinants and their selection in the rapid disease model of neuroAIDS.

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2013-11-01
2020-01-18
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References

  1. Archer J. , Pinney J. W. , Fan J. , Simon-Loriere E. , Arts E. J. , Negroni M. , Robertson D. L. . ( 2008; ). Identifying the important HIV-1 recombination breakpoints. . PLOS Comput Biol 4:, e1000178. [CrossRef] [PubMed]
    [Google Scholar]
  2. Baird H. A. , Gao Y. , Galetto R. , Lalonde M. , Anthony R. M. , Giacomoni V. , Abreha M. , Destefano J. J. , Negroni M. , Arts E. J. . ( 2006; ). Influence of sequence identity and unique breakpoints on the frequency of intersubtype HIV-1 recombination. . Retrovirology 3:, 91. [CrossRef] [PubMed]
    [Google Scholar]
  3. Baril M. , Dulude D. , Steinberg S. V. , Brakier-Gingras L. . ( 2003; ). The frameshift stimulatory signal of human immunodeficiency virus type 1 group O is a pseudoknot. . J Mol Biol 331:, 571–583. [CrossRef] [PubMed]
    [Google Scholar]
  4. Bruen T. C. , Philippe H. , Bryant D. . ( 2006; ). A simple and robust statistical test for detecting the presence of recombination. . Genetics 172:, 2665–2681. [CrossRef] [PubMed]
    [Google Scholar]
  5. Burdo T. H. , Soulas C. , Orzechowski K. , Button J. , Krishnan A. , Sugimoto C. , Alvarez X. , Kuroda M. J. , Williams K. C. . ( 2010; ). Increased monocyte turnover from bone marrow correlates with severity of SIV encephalitis and CD163 levels in plasma. . PLoS Pathog 6:, e1000842. [CrossRef] [PubMed]
    [Google Scholar]
  6. Chen J. H. , Le S. Y. , Maizel J. V. . ( 1992; ). A procedure for RNA pseudoknot prediction. . Comput Appl Biosci 8:, 243–248.[PubMed]
    [Google Scholar]
  7. Chen J. , Rhodes T. D. , Hu W. S. . ( 2005; ). Comparison of the genetic recombination rates of human immunodeficiency virus type 1 in macrophages and T cells. . J Virol 79:, 9337–9340. [CrossRef] [PubMed]
    [Google Scholar]
  8. Coffin J. M. . ( 1979; ). Structure, replication, and recombination of retrovirus genomes: some unifying hypotheses. . J Gen Virol 42:, 1–26. [CrossRef] [PubMed]
    [Google Scholar]
  9. Coffin J. M. . ( 1995; ). HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. . Science 267:, 483–489. [CrossRef] [PubMed]
    [Google Scholar]
  10. Crotty S. , Miller C. J. , Lohman B. L. , Neagu M. R. , Compton L. , Lu D. , F. X. , Fritts L. , Lifson J. D. , Andino R. . ( 2001; ). Protection against simian immunodeficiency virus vaginal challenge by using Sabin poliovirus vectors. . J Virol 75:, 7435–7452. [CrossRef] [PubMed]
    [Google Scholar]
  11. Delport W. , Poon A. F. , Frost S. D. , Kosakovsky Pond S. L. . ( 2010; ). Datamonkey 2010: a suite of phylogenetic analysis tools for evolutionary biology. . Bioinformatics 26:, 2455–2457. [CrossRef] [PubMed]
    [Google Scholar]
  12. Ding Y. , Chan C. Y. , Lawrence C. E. . ( 2005; ). RNA secondary structure prediction by centroids in a Boltzmann weighted ensemble. . RNA 11:, 1157–1166. [CrossRef] [PubMed]
    [Google Scholar]
  13. Galiwango R. M. , Lamers S. L. , Redd A. D. , Manucci J. , Tobian A. A. , Sewankambo N. , Kigozi G. , Nakigozi G. , Serwadda D. . & other authors ( 2012; ). HIV type 1 genetic variation in foreskin and blood from subjects in Rakai, Uganda. . AIDS Res Hum Retroviruses 28:, 729–733.[PubMed] [CrossRef]
    [Google Scholar]
  14. Gao F. , Robertson D. L. , Morrison S. G. , Hui H. , Craig S. , Decker J. , Fultz P. N. , Girard M. , Shaw G. M. . & other authors ( 1996; ). The heterosexual human immunodeficiency virus type 1 epidemic in Thailand is caused by an intersubtype (A/E) recombinant of African origin. . J Virol 70:, 7013–7029.[PubMed]
    [Google Scholar]
  15. Gruber A. R. , Lorenz R. , Bernhart S. H. , Neuböck R. , Hofacker I. L. . ( 2008; ). The Vienna RNA websuite. . Nucleic Acids Res 36: (Web Server issue), W70–W74. [CrossRef] [PubMed]
    [Google Scholar]
  16. Hoxie J. A. . ( 1991; ). Hypothetical assignment of intrachain disulfide bonds for HIV-2 and SIV envelope glycoproteins. . AIDS Res Hum Retroviruses 7:, 495–499. [CrossRef] [PubMed]
    [Google Scholar]
  17. Huson D. H. . ( 1998; ). SplitsTree: analyzing and visualizing evolutionary data. . Bioinformatics 14:, 68–73. [CrossRef] [PubMed]
    [Google Scholar]
  18. Huson D. H. , Bryant D. . ( 2006; ). Application of phylogenetic networks in evolutionary studies. . Mol Biol Evol 23:, 254–267. [CrossRef] [PubMed]
    [Google Scholar]
  19. Jetzt A. E. , Yu H. , Klarmann G. J. , Ron Y. , Preston B. D. , Dougherty J. P. . ( 2000; ). High rate of recombination throughout the human immunodeficiency virus type 1 genome. . J Virol 74:, 1234–1240. [CrossRef] [PubMed]
    [Google Scholar]
  20. Kijak G. H. , McCutchan F. E. . ( 2005; ). HIV diversity, molecular epidemiology, and the role of recombination. . Curr Infect Dis Rep 7:, 480–488. [CrossRef] [PubMed]
    [Google Scholar]
  21. Kuhner M. K. , Yamato J. , Felsenstein J. . ( 2000; ). Maximum likelihood estimation of recombination rates from population data. . Genetics 156:, 1393–1401.[PubMed]
    [Google Scholar]
  22. Lamers S. L. , Sleasman J. W. , Goodenow M. M. . ( 1996; ). A model for alignment of Env V1 and V2 hypervariable domains from human and simian immunodeficiency viruses. . AIDS Res Hum Retroviruses 12:, 1169–1178. [CrossRef] [PubMed]
    [Google Scholar]
  23. Lamers S. L. , Salemi M. , Galligan D. C. , de Oliveira T. , Fogel G. B. , Granier S. C. , Zhao L. , Brown J. N. , Morris A. . & other authors ( 2009; ). Extensive HIV-1 intra-host recombination is common in tissues with abnormal histopathology. . PLoS ONE 4:, e5065. [CrossRef] [PubMed]
    [Google Scholar]
  24. Lamers S. L. , Salemi M. , Galligan D. C. , Morris A. , Gray R. , Fogel G. , Zhao L. , McGrath M. S. . ( 2010; ). Human immunodeficiency virus-1 evolutionary patterns associated with pathogenic processes in the brain. . J Neurovirol 16:, 230–241. [CrossRef] [PubMed]
    [Google Scholar]
  25. Levy D. N. , Aldrovandi G. M. , Kutsch O. , Shaw G. M. . ( 2004; ). Dynamics of HIV-1 recombination in its natural target cells. . Proc Natl Acad Sci U S A 101:, 4204–4209. [CrossRef] [PubMed]
    [Google Scholar]
  26. Lifson A. R. , Thai D. , Hang K. . ( 2001a; ). Lack of immunization documentation in Minnesota refugees: challenges for refugee preventive health care. . J Immigr Health 3:, 47–52. [CrossRef] [PubMed]
    [Google Scholar]
  27. Lifson J. D. , Rossio J. L. , Piatak M. Jr , Parks T. , Li L. , Kiser R. , Coalter V. , Fisher B. , Flynn B. M. . & other authors ( 2001b; ). Role of CD8+ lymphocytes in control of simian immunodeficiency virus infection and resistance to rechallenge after transient early antiretroviral treatment. . J Virol 75:, 10187–10199. [CrossRef] [PubMed]
    [Google Scholar]
  28. Liu B. , Mathews D. H. , Turner D. H. . ( 2010; ). RNA pseudoknots: folding and finding. . F1000 Biol Rep 2:, 8.[PubMed] [CrossRef]
    [Google Scholar]
  29. Mankowski J. L. , Clements J. E. , Zink M. C. . ( 2002; ). Searching for clues: tracking the pathogenesis of human immunodeficiency virus central nervous system disease by use of an accelerated, consistent simian immunodeficiency virus macaque model. . J Infect Dis 186: (Suppl 2), S199–S208. [CrossRef] [PubMed]
    [Google Scholar]
  30. Mild M. , Esbjörnsson J. , Fenyö E. M. , Medstrand P. . ( 2007; ). Frequent intrapatient recombination between human immunodeficiency virus type 1 R5 and X4 envelopes: implications for coreceptor switch. . J Virol 81:, 3369–3376. [CrossRef] [PubMed]
    [Google Scholar]
  31. Negroni M. , Ricchetti M. , Nouvel P. , Buc H. . ( 1995; ). Homologous recombination promoted by reverse transcriptase during copying of two distinct RNA templates. . Proc Natl Acad Sci U S A 92:, 6971–6975. [CrossRef] [PubMed]
    [Google Scholar]
  32. Ng O. T. , Munshaw S. , Lamers S. L. , Chew K. K. , Lin L. , Redd A. D. , Manucci J. , Quinn T. C. , Ray S. C. . & other authors ( 2011; ). Molecular epidemiology of HIV type 1 in Singapore and identification of novel CRF01_AE/B recombinant forms. . AIDS Res Hum Retroviruses 27:, 1135–1137. [CrossRef] [PubMed]
    [Google Scholar]
  33. Orenstein J. M. , Fox C. , Wahl S. M. . ( 1997; ). Macrophages as a source of HIV during opportunistic infections. . Science 276:, 1857–1861. [CrossRef] [PubMed]
    [Google Scholar]
  34. Palmer S. , Kearney M. , Maldarelli F. , Halvas E. K. , Bixby C. J. , Bazmi H. , Rock D. , Falloon J. , Davey R. T. Jr . & other authors ( 2005; ). Multiple, linked human immunodeficiency virus type 1 drug resistance mutations in treatment-experienced patients are missed by standard genotype analysis. . J Clin Microbiol 43:, 406–413. [CrossRef] [PubMed]
    [Google Scholar]
  35. Posada D. , Crandall K. A. . ( 2001; ). Evaluation of methods for detecting recombination from DNA sequences: computer simulations. . Proc Natl Acad Sci U S A 98:, 13757–13762. [CrossRef] [PubMed]
    [Google Scholar]
  36. Ratai E. M. , Pilkenton S. , He J. , Fell R. , Bombardier J. P. , Joo C. G. , Lentz M. R. , Kim W. K. , Burdo T. H. . & other authors ( 2011; ). CD8+ lymphocyte depletion without SIV infection does not produce metabolic changes or pathological abnormalities in the rhesus macaque brain. . J Med Primatol 40:, 300–309. [CrossRef] [PubMed]
    [Google Scholar]
  37. Reeder J. , Steffen P. , Giegerich R. . ( 2007; ). pknotsRG: RNA pseudoknot folding including near-optimal structures and sliding windows. . Nucleic Acids Res 35: (Web Server issue), W320–W324. [CrossRef] [PubMed]
    [Google Scholar]
  38. Sabino E. C. , Shpaer E. G. , Morgado M. G. , Korber B. T. , Diaz R. S. , Bongertz V. , Cavalcante S. , Galvão-Castro B. , Mullins J. I. , Mayer A. . ( 1994; ). Identification of human immunodeficiency virus type 1 envelope genes recombinant between subtypes B and F in two epidemiologically linked individuals from Brazil. . J Virol 68:, 6340–6346.[PubMed]
    [Google Scholar]
  39. Salemi M. , Gray R. R. , Goodenow M. M. . ( 2008; ). An exploratory algorithm to identify intra-host recombinant viral sequences. . Mol Phylogenet Evol 49:, 618–628. [CrossRef] [PubMed]
    [Google Scholar]
  40. Salemi M. , Vandamme A.-M. , Lemey P. . ( 2009; ). The Phylogenetic Handbook: A Practical Approach to Phylogenetic Analysis and Hypothesis Testing. Cambridge:: Cambridge University Press;.
    [Google Scholar]
  41. Salminen M. O. , Carr J. K. , Burke D. S. , McCutchan F. E. . ( 1995; ). Identification of breakpoints in intergenotypic recombinants of HIV type 1 by bootscanning. . AIDS Res Hum Retroviruses 11:, 1423–1425. [CrossRef] [PubMed]
    [Google Scholar]
  42. Schmitz G. , Theres K. . ( 1999; ). Genetic control of branching in Arabidopsis and tomato. . Curr Opin Plant Biol 2:, 51–55. [CrossRef] [PubMed]
    [Google Scholar]
  43. Schmitz J. E. , Kuroda M. J. , Santra S. , Sasseville V. G. , Simon M. A. , Lifton M. A. , Racz P. , Tenner-Racz K. , Dalesandro M. . & other authors ( 1999; ). Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. . Science 283:, 857–860. [CrossRef] [PubMed]
    [Google Scholar]
  44. Sellman J. S. , Lifson A. R. . ( 2001; ). AIDS in Africa. A global responsibility. . Minn Med 84:, 22–26.[PubMed]
    [Google Scholar]
  45. Shriner D. , Rodrigo A. G. , Nickle D. C. , Mullins J. I. . ( 2004; ). Pervasive genomic recombination of HIV-1 in vivo. . Genetics 167:, 1573–1583. [CrossRef] [PubMed]
    [Google Scholar]
  46. Simmonds P. , Balfe P. , Ludlam C. A. , Bishop J. O. , Brown A. J. . ( 1990; ). Analysis of sequence diversity in hypervariable regions of the external glycoprotein of human immunodeficiency virus type 1. . J Virol 64:, 5840–5850.[PubMed]
    [Google Scholar]
  47. Sperschneider J. , Datta A. . ( 2008; ). KnotSeeker: heuristic pseudoknot detection in long RNA sequences. . RNA 14:, 630–640. [CrossRef] [PubMed]
    [Google Scholar]
  48. Strickland S. L. , Gray R. R. , Lamers S. L. , Burdo T. H. , Huenink E. , Nolan D. J. , Nowlin B. , Alvarez X. , Midkiff C. C. . & other authors ( 2011; ). Significant genetic heterogeneity of the SIVmac251 viral swarm derived from different sources. . AIDS Res Hum Retroviruses 27:, 1327–1332. [CrossRef] [PubMed]
    [Google Scholar]
  49. Strickland S. L. , Gray R. R. , Lamers S. L. , Burdo T. H. , Huenink E. , Nolan D. J. , Nowlin B. , Alvarez X. , Midkiff C. C. . & other authors ( 2012; ). Efficient transmission and persistence of low-frequency SIVmac251 variants in CD8-depleted rhesus macaques with different neuropathology. . J Gen Virol 93:, 925–938. [CrossRef] [PubMed]
    [Google Scholar]
  50. Svarovskaia E. S. , Delviks K. A. , Hwang C. K. , Pathak V. K. . ( 2000; ). Structural determinants of murine leukemia virus reverse transcriptase that affect the frequency of template switching. . J Virol 74:, 7171–7178. [CrossRef] [PubMed]
    [Google Scholar]
  51. Swingler S. , Mann A. M. , Zhou J. , Swingler C. , Stevenson M. . ( 2007; ). Apoptotic killing of HIV-1-infected macrophages is subverted by the viral envelope glycoprotein. . PLoS Pathog 3:, e134. [CrossRef] [PubMed]
    [Google Scholar]
  52. Walshe R. , Schmitz N. , Diehl V. . ( 1999; ). Can corporatization contribute to quality assurance and cost control in the German hospital sector? A pilot project for stem cell transplantation. . Health Policy 48:, 207–218. [CrossRef] [PubMed]
    [Google Scholar]
  53. Watts J. M. , Dang K. K. , Gorelick R. J. , Leonard C. W. , Bess J. W. Jr , Swanstrom R. , Burch C. L. , Weeks K. M. . ( 2009; ). Architecture and secondary structure of an entire HIV-1 RNA genome. . Nature 460:, 711–716. [CrossRef] [PubMed]
    [Google Scholar]
  54. Williams K. , Burdo T. H. . ( 2012; ). Monocyte mobilization, activation markers, and unique macrophage populations in the brain: observations from SIV infected monkeys are informative with regard to pathogenic mechanisms of HIV infection in humans. . J Neuroimmune Pharmacol 7:, 363–371. [CrossRef] [PubMed]
    [Google Scholar]
  55. Wills N. M. , Gesteland R. F. , Atkins J. F. . ( 1994; ). Pseudoknot-dependent read-through of retroviral gag termination codons: importance of sequences in the spacer and loop 2. . EMBO J 13:, 4137–4144.[PubMed]
    [Google Scholar]
  56. Wood N. , Bhattacharya T. , Keele B. F. , Giorgi E. , Liu M. , Gaschen B. , Daniels M. , Ferrari G. , Haynes B. F. . & other authors ( 2009; ). HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of APOBEC. . PLoS Pathog 5:, e1000414. [CrossRef] [PubMed]
    [Google Scholar]
  57. Zuker M. , Stiegler P. . ( 1981; ). Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information. . Nucleic Acids Res 9:, 133–148. [CrossRef] [PubMed]
    [Google Scholar]
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