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Sub-Class Differences of PH-Dependent HIV GP120-CD4 Interactions

Published:15 August 2018Publication History

ABSTRACT

Research in the field of HIV transmission has yet to provide a vaccine for this imponderable virus. Though progress has been made to extend the life of those chronically infected, a solution to the transmission of the disease remains elusive. Previous studies involving electrostatic surface charge analysis revealed the sensitivity of gp120 envelope (Env) protein function to changes in pH across levels consistent with those found in the human body. A prototype computational approach was developed and found to agree with these results. A refined process was developed capable of classifying Env sequences/structures through machine learning techniques. We expound this analytical procedure to encompass residue-level analysis and include minimization steps to ensure the integrity of the protein models. Additionally, the process has been enhanced with advanced data compression techniques to allow for more in-depth analysis of the systems. In this research we explore a new technique termed electrostatic variance masking (EVM), that reveals what we hypothesize to be the mechanistic residues responsible for the pH sensitivity of Env binding site. The data implies that a conserved set of core residues may be responsible for modulation of the binding process in varying environmental conditions mainly involving pH.

References

  1. M-R Abrahams and et al. . 2009. Quantitating the multiplicity of infection with human immunodeficiency virus type 1 subtype C reveals a non-poisson distribution of transmitted variants. Journal of Virology Vol. 83, 8 (Apr . 2009), 3556--67.Google ScholarGoogle ScholarCross RefCross Ref
  2. N A Baker and et al. . 2001. Electrostatics of nanosystems: application to microtubules and the ribosome. Proceedings of the National Academy of Sciences of the United States of America Vol. 98, 18 (2001), 10037--41.Google ScholarGoogle ScholarCross RefCross Ref
  3. Katharine J Bar and et al. . 2012. Early low-titer neutralizing antibodies impede HIV-1 replication and select for virus escape. PLoS Pathogens Vol. 8, 5 (2012), e1002721.Google ScholarGoogle ScholarCross RefCross Ref
  4. Dan H Barouch and et al. . 2013. Protective efficacy of a global HIV-1 mosaic vaccine against heterologous SHIV challenges in rhesus monkeys. Cell Vol. 155, 3 (Oct . 2013), 531--9.Google ScholarGoogle ScholarCross RefCross Ref
  5. H.J.C. Berendsen, D. van der Spoel, and R. van Drunen . 1995. GROMACS: A message-passing parallel molecular dynamics implementation. Computer Physics Communications Vol. 91, 1--3 (sep . 1995), 43--56.Google ScholarGoogle ScholarCross RefCross Ref
  6. D. I. Boeras and et al. . 2011. Role of donor genital tract HIV-1 diversity in the transmission bottleneck. Proceedings of the National Academy of Sciences Vol. 108, 46 (2011), E1156--E1163.Google ScholarGoogle ScholarCross RefCross Ref
  7. Evelien M Bunnik and et al. . 2008. Autologous neutralizing humoral immunity and evolution of the viral envelope in the course of subtype B human immunodeficiency virus type 1 infection. Journal of Virology Vol. 82, 16 (Aug . 2008), 7932--41.Google ScholarGoogle ScholarCross RefCross Ref
  8. Dennis R Burton and et al. . 2012. Broadly neutralizing antibodies present new prospects to counter highly antigenically diverse viruses. Science (New York, N.Y.) Vol. 337, 6091 (Jul . 2012), 183--6.Google ScholarGoogle Scholar
  9. Laurent Dacheux and et al. . 2004. Evolutionary dynamics of the glycan shield of the human immunodeficiency virus envelope during natural infection and implications for exposure of the 2G12 epitope. Journal of Virology Vol. 78, 22 (Nov . 2004), 12625--37.Google ScholarGoogle ScholarCross RefCross Ref
  10. Scott Deerwester, Susan T. Dumais, and Richard Harshman . 1990. Indexing by Latent Symantic Analysis. Journal of the American Society for Information Science and Technology Vol. 41, 6 (1990), 391--407. deftempurl%http://www.psychology.uwo.ca/faculty/harshman/latentsa.pdf tempurlGoogle ScholarGoogle ScholarCross RefCross Ref
  11. Narayanan Eswar and et al. . 2002. Comparative protein structure modeling using modeller. John Wiley & Sons, Inc.Google ScholarGoogle Scholar
  12. Kelly M. Fahrbach, Olga Malykhina, Daniel J. Stieh, and Thomas J. Hope . 2013. Differential Binding of IgG and IgA to Mucus of the Female Reproductive Tract. PLOS ONE Vol. 8, 10 (10 . 2013), 1--11.Google ScholarGoogle Scholar
  13. Daniel W. Farrell, Kirill Speranskiy, and M. F. Thorpe . 2010. Generating stereochemically acceptable protein pathways. Proteins: Structure, Function and Bioinformatics Vol. 78, 14 (2010), 2908--2921.Google ScholarGoogle ScholarCross RefCross Ref
  14. Will Fischer and et. al. . 2007. Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nature Medicine Vol. 13, 1 (Jan . 2007), 100--6.Google ScholarGoogle ScholarCross RefCross Ref
  15. Brian Thomas Foley and et al. . 2015. HIV Sequence Compendium 2015. (10 . 2015).Google ScholarGoogle Scholar
  16. Jonathan Howton . 2017. A Computational Electrostratic Modeling Pipeline for Comparing pH-dependent gp120-CD4 Interactions in Founder and Chronic HIV Strains. Master's thesis. bibinfoschoolMiddle Tennessee State University, Murfreesboro, TN. deftempurl%http://jewlscholar.mtsu.edu/xmlui/handle/mtsu/5324 tempurlGoogle ScholarGoogle Scholar
  17. Jonathan Howton and Joshua L. Phillips . 2017. Computational Modeling of pH-dependent gp120-CD4 Interactions in Founder and Chronic HIV Strains. In Proceedings of the 8th ACM International Conference on Bioinformatics, Computational Biology,and Health Informatics - ACM-BCB '17. ACM Press, Boston, MA, USA, 644--649. Google ScholarGoogle ScholarDigital LibraryDigital Library
  18. William Humphrey, Andrew Dalke, and Klaus Schulten . 1996. VMD -- Visual Molecular Dynamics. Journal of Molecular Graphics Vol. 14 (1996), 33--38.Google ScholarGoogle ScholarCross RefCross Ref
  19. Kazutaka Katoh and Daron M. Standley . 2013. MAFFT multiple sequence alignment software version 7: Improvements in performance and usability. Molecular Biology and Evolution Vol. 30, 4 (2013), 772--780.Google ScholarGoogle ScholarCross RefCross Ref
  20. Brandon F Keele and et al. . 2008. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proceedings of the National Academy of Sciences of the United States of America Vol. 105, 21 (2008), 7552--7.Google ScholarGoogle ScholarCross RefCross Ref
  21. Korber and et al. . 2017. HXB2 Annotated Spreadsheet. deftempurl%https://www.hiv.lanl.gov/content/sequence/HIV/MAP/hxb2.xls Retrieved June 24,2018 from tempurlGoogle ScholarGoogle Scholar
  22. Bette Korber and S. Gnanakaran . 2011. Converging on an HIV Vaccine. Science Vol. 333, 6049 (2011), 1589--1590.Google ScholarGoogle ScholarCross RefCross Ref
  23. B Korber-Irrgang and et al. . 1998. Numbering positions in HIV relative to HXB2CG. deftempurl%https://www.scienceopen.com/document?vid=2661d7cb-fb50--4a20--9044--71a8501579f3 tempurlGoogle ScholarGoogle Scholar
  24. Denise L Kothe and et al. . 2006. Ancestral and consensus envelope immunogens for HIV-1 subtype C. Virology Vol. 352, 2 (Sep . 2006), 438--49.Google ScholarGoogle ScholarCross RefCross Ref
  25. Bing Li and et al. . 2006. Evidence for potent autologous neutralizing antibody titers and compact envelopes in early infection with subtype C human immunodeficiency virus type 1. Journal of Virology Vol. 80, 11 (Jun . 2006), 5211--8.Google ScholarGoogle ScholarCross RefCross Ref
  26. Hua-Xin Liao and et al. . 2013. Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2. Immunity Vol. 38, 1 (Jan . 2013), 176--86.Google ScholarGoogle ScholarCross RefCross Ref
  27. Erik Lindahl, Berk Hess, and David van der Spoel . 2001. GROMACS 3.0: a package for molecular simulation and trajectory analysis. Journal of Molecular Modeling Vol. 7, 8 (Aug . 2001), 306--317.Google ScholarGoogle ScholarCross RefCross Ref
  28. P. Lindstrom . 2014. Fixed-Rate Compressed Floating-Point Arrays. IEEE Trans. on Visualzation and Computer Graphics Vol. 20, 12 (2014), 2674--2683.Google ScholarGoogle ScholarCross RefCross Ref
  29. Michael K P Liu and et al. . 2013. Vertical T cell immunodominance and epitope entropy determine HIV-1 escape. The Journal of clinical investigation Vol. 123, 1 (jan . 2013), 380--93.Google ScholarGoogle Scholar
  30. Aaron C. Mason and Jan H. Jensen . 2008. Protein-protein binding is often associated with changes in protonation state. Proteins: Structure, Function and Genetics Vol. 71, 1 (2008), 81--91.Google ScholarGoogle ScholarCross RefCross Ref
  31. Scott P. Morton, Julie B. Phillips, and Joshua L. Phillips . 2017. High-Throughput Structural Modeling of the HIV Transmission Bottleneck Proceedings of the 2017 IEEE International Conference on Bioinformatics and Biomedicine - BIBM-HPCB '17. IEEE Press, Kansas City, MO, USA.Google ScholarGoogle Scholar
  32. David C. Nickle and et al. . 2007. HIV-Specific Probabilistic Models of Protein Evolution. PLoS ONE Vol. 2, 6 (2007).Google ScholarGoogle Scholar
  33. Emmanuel Paradis, Julien Claude, and Korbinian Strimmer . 2004. APE: Analyses of phylogenetics and evolution in R language. Bioinformatics Vol. 20, 2 (2004), 289--290. Google ScholarGoogle ScholarDigital LibraryDigital Library
  34. Nicholas F Parrish and et. al. . 2013. Phenotypic properties of transmitted founder HIV-1. Proceedings of the National Academy of Sciences of the United States of America Vol. 110, 17 (2013), 6626--33.Google ScholarGoogle ScholarCross RefCross Ref
  35. Joshua L. Phillips and S. Gnanakaran . 2015. A data-driven approach to modeling the tripartite structure of multidrug resistance efflux pumps. Proteins: Structure, Function and Bioinformatics Vol. 83, 1 (2015), 46--65.Google ScholarGoogle ScholarCross RefCross Ref
  36. Jesus F Salazar-Gonzalez and et al. . 2009. Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection. The Journal of Experimental Medicine Vol. 206, 6 (Jun . 2009), 1273--89.Google ScholarGoogle ScholarCross RefCross Ref
  37. Alexandros Stamatakis . 2014. RAxML version 8: A tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics Vol. 30, 9 (2014), 1312--1313.Google ScholarGoogle ScholarCross RefCross Ref
  38. Daniel J. Stieh and et al. . 2013. Dynamic electrophoretic fingerprinting of the HIV-1 envelope glycoprotein. Retrovirology Vol. 10, 1 (2013), 33.Google ScholarGoogle ScholarCross RefCross Ref
  39. Emma L Turnbull and et al. . 2009. Kinetics of expansion of epitope-specific T cell responses during primary HIV-1 infection. Journal of Immunology (Baltimore, Md. : 1950) Vol. 182, 11 (Jun . 2009), 7131--45.Google ScholarGoogle Scholar
  40. Xiping Wei and et al. . 2003. Antibody neutralization and escape by HIV-1. Nature Vol. 422, 6929 (Mar . 2003), 307--12.Google ScholarGoogle ScholarCross RefCross Ref
  41. R Wyatt and et al. . 1998. The antigenic structure of the HIV gp120 envelope glycoprotein. Nature Vol. 393, 6686 (Jun . 1998), 705--11.Google ScholarGoogle ScholarCross RefCross Ref

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              cover image ACM Conferences
              BCB '18: Proceedings of the 2018 ACM International Conference on Bioinformatics, Computational Biology, and Health Informatics
              August 2018
              727 pages
              ISBN:9781450357944
              DOI:10.1145/3233547

              Copyright © 2018 ACM

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              Publication History

              • Published: 15 August 2018

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              BCB '18 Paper Acceptance Rate46of148submissions,31%Overall Acceptance Rate254of885submissions,29%

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