Potential immune escape mutations under inferred selection pressure in HIV-1 strains circulating in Medellín, Colombia

The introduction of highly active antiretroviral therapy (HAART) has significantly improved life expectancy of HIV-infected patients; nevertheless, it does not eliminate the virus from hosts, so a cure for this infection is crucial. Some strategies have employed the induction of anti-HIV CD8+ T cell...

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Autores:
Arcia, David
Ochoa, Rodrigo
Hernández López, Juan Carlos
Álvarez, Cristiam M.
Diaz, Francisco Javier
Velilla Hernandez, Paula Andrea
Acevedo Sáenz, Liliana
Tipo de recurso:
Article of journal
Fecha de publicación:
2019
Institución:
Universidad Cooperativa de Colombia
Repositorio:
Repositorio UCC
Idioma:
OAI Identifier:
oai:repository.ucc.edu.co:20.500.12494/15939
Acceso en línea:
https://hdl.handle.net/20.500.12494/15939
Palabra clave:
Epitopes
HIV-1
HLA-B
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openAccess
License
Atribución
id COOPER2_3056ff063dce3746c63f72cc95fc7847
oai_identifier_str oai:repository.ucc.edu.co:20.500.12494/15939
network_acronym_str COOPER2
network_name_str Repositorio UCC
repository_id_str
dc.title.spa.fl_str_mv Potential immune escape mutations under inferred selection pressure in HIV-1 strains circulating in Medellín, Colombia
title Potential immune escape mutations under inferred selection pressure in HIV-1 strains circulating in Medellín, Colombia
spellingShingle Potential immune escape mutations under inferred selection pressure in HIV-1 strains circulating in Medellín, Colombia
Epitopes
HIV-1
HLA-B
title_short Potential immune escape mutations under inferred selection pressure in HIV-1 strains circulating in Medellín, Colombia
title_full Potential immune escape mutations under inferred selection pressure in HIV-1 strains circulating in Medellín, Colombia
title_fullStr Potential immune escape mutations under inferred selection pressure in HIV-1 strains circulating in Medellín, Colombia
title_full_unstemmed Potential immune escape mutations under inferred selection pressure in HIV-1 strains circulating in Medellín, Colombia
title_sort Potential immune escape mutations under inferred selection pressure in HIV-1 strains circulating in Medellín, Colombia
dc.creator.fl_str_mv Arcia, David
Ochoa, Rodrigo
Hernández López, Juan Carlos
Álvarez, Cristiam M.
Diaz, Francisco Javier
Velilla Hernandez, Paula Andrea
Acevedo Sáenz, Liliana
dc.contributor.author.none.fl_str_mv Arcia, David
Ochoa, Rodrigo
Hernández López, Juan Carlos
Álvarez, Cristiam M.
Diaz, Francisco Javier
Velilla Hernandez, Paula Andrea
Acevedo Sáenz, Liliana
dc.subject.spa.fl_str_mv Epitopes
HIV-1
HLA-B
topic Epitopes
HIV-1
HLA-B
description The introduction of highly active antiretroviral therapy (HAART) has significantly improved life expectancy of HIV-infected patients; nevertheless, it does not eliminate the virus from hosts, so a cure for this infection is crucial. Some strategies have employed the induction of anti-HIV CD8+ T cells. However, the high genetic variability of HIV-1 represents the biggest obstacle for these strategies, since immune escape mutations within epitopes restricted by Human Leukocyte Antigen class I molecules (HLA-I) abrogate the antiviral activity of these cells. We used a bioinformatics pipeline for the determination of such mutations, based on selection pressure and docking/refinement analyses. Fifty HIV-1 infected patients were recruited; HLA-A and HLA-B alleles were typified using sequence-specific oligonucleotide approach, and viral RNA was extracted for the amplification of HIV-1 gag, which was bulk sequenced and aligned to perform selection pressure analysis, using Single Likelihood Ancestor Counting (SLAC) and Fast Unconstrained Bayesian Approximation (FUBAR) algorithms. Positively selected sites were mapped into HLA-I-specific epitopes, and both mutated and wild type epitopes were modelled using PEP-FOLD. Molecular docking and refinement assays were carried out using AutoDock Vina 4 and FlexPepDock. Five positively selected sites were found: S54 at HLA-A*02 GC9, T84 at HLA-A*02 SL9, S125 at HLA-B*35 HY9, S173 at HLA-A*02/B*57 KS12 and I223 at HLA-B*35 HA9. Although some mutations have been previously described as immune escape mutations, the majority of them have not been reported. Molecular docking/refinement analysis showed that one combination of mutations at GC9, one at SL9, and eight at HY9 epitopes could act as immune escape mutations. Moreover, HLA-A*02-positive patients harbouring mutations at KS12, and HLA-B*35-positive patients with mutations at HY9 have significantly higher plasma viral loads than patients lacking such mutations. Thus, HLA-A and -B alleles could be shaping the genetic diversity of HIV-1 through the selection of potential immune escape mutations.
publishDate 2019
dc.date.issued.none.fl_str_mv 2019-04
dc.date.accessioned.none.fl_str_mv 2020-01-15T18:59:59Z
dc.date.available.none.fl_str_mv 2020-01-15T18:59:59Z
2022-06-30
dc.type.none.fl_str_mv Artículo
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.coar.none.fl_str_mv http://purl.org/coar/resource_type/c_6501
dc.type.coarversion.none.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/article
dc.type.version.none.fl_str_mv info:eu-repo/semantics/publishedVersion
format http://purl.org/coar/resource_type/c_6501
status_str publishedVersion
dc.identifier.issn.spa.fl_str_mv 1567-1348
dc.identifier.uri.spa.fl_str_mv 10.1016/j.meegid.2018.07.001
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12494/15939
dc.identifier.bibliographicCitation.spa.fl_str_mv Arcia, D., Ochoa, R., Hernández, J. C., Álvarez, C. M., Díaz, F. J., Velilla, P. A. y Acevedo Sáenz, L. (2018). Potential immune escape mutations under inferred selection pressure in HIV-1 strains circulating in Medellín, Colombia. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 69: 267-278. 2019. Recuperado de:
identifier_str_mv 1567-1348
10.1016/j.meegid.2018.07.001
Arcia, D., Ochoa, R., Hernández, J. C., Álvarez, C. M., Díaz, F. J., Velilla, P. A. y Acevedo Sáenz, L. (2018). Potential immune escape mutations under inferred selection pressure in HIV-1 strains circulating in Medellín, Colombia. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 69: 267-278. 2019. Recuperado de:
url https://hdl.handle.net/20.500.12494/15939
dc.relation.isversionof.spa.fl_str_mv https://www.sciencedirect.com/science/article/abs/pii/S1567134818304714?via%3Dihub
dc.relation.ispartofjournal.spa.fl_str_mv Infection, Genetics and Evolution
dc.relation.references.spa.fl_str_mv Abram, M.E., Ferris, A.L., Shao, W., Alvord, W.G., Hughes, S.H., 2010. Nature, position, and frequency of mutations made in a single cycle of HIV-1 replication. J. Virol. 84 (19), 9864–9878. https://doi.org/10.1128/jvi.00915-10. PubMed PMID: 20660205.
Acevedo-Saenz, L., Ochoa, R., Rugeles, M.T., Olaya-Garcia, P., Velilla-Hernandez, P.A., Diaz, F.J., 2015. Selection pressure in CD8(+) T-cell epitopes in the pol gene of HIV- 1 infected individuals in Colombia. A bioinformatic approach. Viruses 7 (3), 1313–1331. https://doi.org/10.3390/v7031313. PubMed PMID: 25803098
Ahlers, J.D., Belyakov, I.M., Thomas, E.K., Berzofsky, J.A., 2001. High-affinity T helper epitope induces complementary helper and APC polarization, increased CTL, and protection against viral infection. J. Clin. Invest. 108 (11), 1677–1685. https://doi. org/10.1172/JCI13463. PubMed PMID: 11733563; PubMed Central PMCID: PMC200990.
Ammaranond, P., van Bockel, D.J., Petoumenos, K., McMurchie, M., Finlayson, R., Middleton, M.G., et al., 2011. HIV immune escape at an immunodominant epitope in HLA-B*27-positive individuals predicts viral load outcome. J. Immunol. 186 (1), 479–488. https://doi.org/10.4049/jimmunol.0903227. PubMed PMID: 21115730.
Arcia, D., Acevedo-Saenz, L., Rugeles, M.T., Velilla, P.A., 2017. Role of CD8+ T cells in the selection of HIV-1 immune escape mutations. Viral Immunol. 30 (1), 3–12. https://doi.org/10.1089/vim.2016.0095. (PubMed PMID: 27805477).
Arts, E.J., Hazuda, D.J., 2012. HIV-1 antiretroviral drug therapy. Cold Spring Harbor Perspectives in Medicine 2 (4), a007161. https://doi.org/10.1101/cshperspect. a007161. PubMed PMID: 22474613.
Bennett, M.S., Joseph, A., Ng, H.L., Goldstein, H., Yang, O.O., 2010. Fine-tuning of T-cell receptor avidity to increase HIV epitope variant recognition by cytotoxic T lymphocytes. AIDS 24 (17), 2619–2628. https://doi.org/10.1097/QAD. 0b013e32833f7b22. (PubMed PMID: 20881472; PubMed Central PMCID: PMC2997528).
Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., et al., 2000. The Protein Data Bank. Nucleic Acids Res. 28 (1), 235–242 (PubMed PMID: 10592235; PubMed Central PMCID: PMCPMC102472).
Borrow, P., Lewicki, H., Hahn, B.H., Shaw, G.M., Oldstone, M.B., 1994. Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection. J Virol 68 (9), 6103–6110 PubMed PMID: 8057491; PubMed Central PMCID: PMC237022.
Brumme, Z.L., Brumme, C.J., Heckerman, D., Korber, B.T., Daniels, M., Carlson, J., et al.,2007. Evidence of differential HLA class I-mediated viral evolution in functional and accessory/regulatory genes of HIV-1. PLoS Pathog. 3 (7), e94. https://doi.org/10. 1371/journal.ppat.0030094. PubMed PMID: 17616974; PubMed Central PMCID: PMC1904471.
Brumme, Z.L., Tao, I., Szeto, S., Brumme, C.J., Carlson, J.M., Chan, D., et al., 2008. Human leukocyte antigen-specific polymorphisms in HIV-1 Gag and their association with viral load in chronic untreated infection. AIDS 22 (11), 1277–1286. https://doi. org/10.1097/QAD.0b013e3283021a8c. PubMed PMID: 18580606.
Cao, J., McNevin, J., Malhotra, U., McElrath, M.J., 2003. Evolution of CD8+ T cell immunity and viral escape following acute HIV-1 infection. J. Immunol. 171 (7), 3837–3846 PubMed PMID: 14500685.
Carlson, J.M., Le, A.Q., Shahid, A., Brumme, Z.L., 2015. HIV-1 adaptation to HLA: a window into virus-host immune interactions. Trends Microbiol. 23 (4), 212–224. https://doi.org/10.1016/j.tim.2014.12.008. PubMed PMID: 25613992.
Crawford, H., Lumm, W., Leslie, A., Schaefer, M., Boeras, D., Prado, J.G., et al., 2009. Evolution of HLA-B*5703 HIV-1 escape mutations in HLA-B*5703-positive individuals and their transmission recipients. J. Exp. Med. 206 (4), 909–921. https:// doi.org/10.1084/jem.20081984. PubMed PMID: 19307327.
Davenport, M.P., Loh, L., Petravic, J., Kent, S.J., 2008. Rates of HIV immune escape and reversion: implications for vaccination. Trends Microbiol. 16 (12), 561–566. https:// doi.org/10.1016/j.tim.2008.09.001. PubMed PMID: 18964018.
Duda, A., Lee-Turner, L., Fox, J., Robinson, N., Dustan, S., Kaye, S., et al., 2009. HLAassociated clinical progression correlates with epitope reversion rates in early human immunodeficiency virus infection. J. Virol. 83 (3), 1228–1239. https://doi.org/10. 1128/jvi.01545-08. PubMed PMID: 19019964.
Eriksson, E.M., Liegler, T., Keh, C.E., Karlsson, A.C., Holditch, S.J., Pilcher, C.D., et al., 2014. Newly exerted T cell pressures on mutated epitopes following transmission help maintain consensus HIV-1 sequences. PLoS One 10 (4), e0120787. https://doi. org/10.1371/journal.pone.0120787. PubMed PMID: 25919393; PubMed Central PMCID: PMC4412704.
Feeney, M.E., Tang, Y., Roosevelt, K.A., Leslie, A.J., McIntosh, K., Karthas, N., et al., 2004. Immune escape precedes breakthrough human immunodeficiency virus type 1 viremia and broadening of the cytotoxic T-lymphocyte response in an HLA-B27-positive long-term-nonprogressing child. J. Virol. 78 (16), 8927–8930. https://doi.org/10. 1128/jvi.78.16.8927-8930.2004. PubMed PMID: 15280502.
Ferrari, G., Korber, B., Goonetilleke, N., Liu, M.K., Turnbull, E.L., Salazar-Gonzalez, J.F., et al., 2011. Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection. PLoS Pathog. 7 (2), e1001273. https://doi.org/10.1371/journal.ppat.1001273. PubMed PMID: 21347345.
Gijsbers, E.F., van Nuenen, A.C., de la Pena, A.T., Bowles, E.J., Stewart-Jones, G.B., Schuitemaker, H., et al., 2014. Low level of HIV-1 evolution after transmission from mother to child. Sci. Rep. 4, 5079. https://doi.org/10.1038/srep05079. PubMed PMID: 24866155.
Goulder, P., Price, D., Nowak, M., Rowland-Jones, S., Phillips, R., McMichael, A., 1997a. Co-evolution of human immunodeficiency virus and cytotoxic T-lymphocyte responses. Immunol. Rev. 159, 17–29 PubMed PMID: 9416500.
Goulder, P.J., Sewell, A.K., Lalloo, D.G., Price, D.A., Whelan, J.A., Evans, J., et al., 1997b. Patterns of immunodominance in HIV-1-specific cytotoxic T lymphocyte responses in two human histocompatibility leukocyte antigens (HLA)-identical siblings with HLAA* 0201 are influenced by epitope mutation. J. Exp. Med. 185 (8), 1423–1433 PubMed PMID: 9126923; PubMed Central PMCID: PMC2196285.
Goulder, P.J., Brander, C., Tang, Y., Tremblay, C., Colbert, R.A., Addo, M.M., et al., 2001. Evolution and transmission of stable CTL escape mutations in HIV infection. Nature 412 (6844), 334–338. https://doi.org/10.1038/35085576. PubMed PMID: 11460164.
HIV Molecular Immunology 2009. http://www.hiv.lanl.gov/content/immunology: Los Alamos National Laboratory, Theoretical Biology and Biophysics, Los Alamos, New Mexico (2009).
Jamieson, B.D., Yang, O.O., Hultin, L., Hausner, M.A., Hultin, P., Matud, J., et al., 2003. Epitope escape mutation and decay of human immunodeficiency virus type 1-specific CTL responses. J. Immunol. 171 (10), 5372–5379 PubMed PMID: 14607940.
Jin, X., Bauer, D.E., Tuttleton, S.E., Lewin, S., Gettie, A., Blanchard, J., et al., 1999. Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian immunodeficiency virus-infected macaques. J. Exp. Med. 189 (6), 991–998 PubMed PMID: 10075982.
Jones, N.A., Wei, X., Flower, D.R., Wong, M., Michor, F., Saag, M.S., et al., 2004. Determinants of human immunodeficiency virus type 1 escape from the primary CD8+ cytotoxic T lymphocyte response. J. Exp. Med. 200 (10), 1243–1256. https:// doi.org/10.1084/jem.20040511. PubMed PMID: 15545352; PubMed Central PMCID: PMC2211924.
Kawashima, Y., Pfafferott, K., Frater, J., Matthews, P., Payne, R., Addo, M., et al., 2009. Adaptation of HIV-1 to human leukocyte antigen class I. Nature 458 (7238), 641–645. https://doi.org/10.1038/nature07746. PubMed PMID: 19242411.
Kearney, M., Maldarelli, F., Shao, W., Margolick, J.B., Daar, E.S., Mellors, J.W., et al., 2009. Human immunodeficiency virus type 1 population genetics and adaptation in newly infected individuals. J. Virol. 83 (6), 2715–2727. https://doi.org/10.1128/ JVI.01960-08. PubMed PMID: 19116249; PubMed Central PMCID: PMC2648286.
Kosakovsky Pond, S.L., Frost, S.D., 2005. Not so different after all: a comparison of methods for detecting amino acid sites under selection. Mol. Biol. Evol. 22 (5), 1208–1222. https://doi.org/10.1093/molbev/msi105. PubMed PMID: 15703242.
Koup, R.A., Safrit, J.T., Cao, Y., Andrews, C.A., McLeod, G., Borkowsky, W., et al., 1994. Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J. Virol. 68 (7), 4650–4655 (PubMed PMID: 8207839).
Kumar, S., Stecher, G., Tamura, K., 2016. MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol. Biol. Evol. 33 (7), 1870–1874. https:// doi.org/10.1093/molbev/msw054. (PubMed PMID: 27004904).
Leslie, A.J., Pfafferott, K.J., Chetty, P., Draenert, R., Addo, M.M., Feeney, M., et al., 2004. HIV evolution: CTL escape mutation and reversion after transmission. Nat. Med. 10 (3), 282–289. https://doi.org/10.1038/nm992. PubMed PMID: 14770175.
Leslie, A., Price, D.A., Mkhize, P., Bishop, K., Rathod, A., Day, C., et al., 2006. Differential selection pressure exerted on HIV by CTL targeting identical epitopes but restricted by distinct HLA alleles from the same HLA supertype. J. Immunol. 177 (7), 4699–4708 PubMed PMID: 16982909.
Llano A, Williams A, Overa A, Silva-Arrieta S, Brander C. HIV molecular immunology 2013. Yusim K, Korber B, Brander C, Barouch D, de Boer R, Haynes B, et al., Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM. LA-UR 13–27758 (2013).
Maartens, G., Celum, C., Lewin, S.R., 2014. HIV infection: epidemiology, pathogenesis, treatment, and prevention. Lancet 384 (9939), 258–271. https://doi.org/10.1016/ s0140-6736(14)60164-1. (PubMed PMID: 24907868).
Martinez-Hackert, E., Anikeeva, N., Kalams, S.A., Walker, B.D., Hendrickson, W.A., Sykulev, Y., 2006. Structural basis for degenerate recognition of natural HIV peptide variants by cytotoxic lymphocytes. J. Biol. Chem. 281 (29), 20205–20212. https:// doi.org/10.1074/jbc.M601934200. PubMed PMID: 16702212.
Mata-Munguia, C., Escoto-Delgadillo, M., Torres-Mendoza, B., Flores-Soto, M., Vazquez- Torres, M., Galvez-Gastelum, F., et al., 2014. Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. BMC Bioinformatics 15, 72. https://doi.org/10.1186/1471-2105-15-72. PubMed PMID: 24629078; PubMed Central PMCID: PMCPMC4003850.
Matsumura, M., Fremont, D.H., Peterson, P.A., Wilson, I.A., 1992. Emerging principles for the recognition of peptide antigens by MHC class I molecules. Science 257 (5072), 927–934 PubMed PMID: 1323878.
Guía de práctica clínica basada en la evidencia científica para la atención de la infección por VIH/Sida en adolescentes (con 13 años de edad o más) y adultos. Ministerio de Salud y Protección Social.
Moir, S., Chun, T.W., Fauci, A.S., 2011. Pathogenic mechanisms of HIV disease. Annu. Rev. Pathol. 6, 223–248. https://doi.org/10.1146/annurev-pathol-011110-130254. PubMed PMID: 21034222.
Moore, C.B., John, M., James, I.R., Christiansen, F.T., Witt, C.S., Mallal, S.A., 2002. Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level. Science 296 (5572), 1439–1443. https://doi.org/10.1126/science.1069660. PubMed PMID: 12029127.
Murrell, B., Moola, S., Mabona, A., Weighill, T., Sheward, D., Kosakovsky Pond, S.L., et al., 2013. FUBAR: a fast, unconstrained bayesian approximation for inferring selection. Mol. Biol. Evol. 30 (5), 1196–1205. https://doi.org/10.1093/molbev/ mst030. PubMed PMID: 23420840.
Nadai, Y., Eyzaguirre, L.M., Constantine, N.T., Sill, A.M., Cleghorn, F., Blattner, W.A., et al., 2008. Protocol for nearly full-length sequencing of HIV-1 RNA from plasma. PLoS One 3 (1), e1420. https://doi.org/10.1371/journal.pone.0001420. (PubMed PMID: 18183300).
Navis, M., Matas, D.E., Rachinger, A., Koning, F.A., van Swieten, P., Kootstra, N.A., et al., 2008. Molecular evolution of human immunodeficiency virus type 1 upon transmission between human leukocyte antigen disparate donor-recipient pairs. PLoS One 3 (6), e2422. https://doi.org/10.1371/journal.pone.0002422. PubMed PMID: 18560583; PubMed Central PMCID: PMC2409968.
Novitsky, V., Wang, R., Margolin, L., Baca, J., Moyo, S., Musonda, R., et al., 2010. Dynamics and timing of in vivo mutations at Gag residue 242 during primary HIV-1 subtype C infection. Virology 403 (1), 37–46. https://doi.org/10.1016/j.virol.2010. 04.001. PubMed PMID: 20444482; PubMed Central PMCID: PMC2884147.
O'Brien, S.J., Gao, X., Carrington, M., 2001. HLA and AIDS: a cautionary tale. Trends Mol. Med. 7 (9), 379–381 PubMed PMID: 11530315.
Pogue, R.R., Eron, J., Frelinger, J.A., Matsui, M., 1995. Amino-terminal alteration of the HLA-A*0201-restricted human immunodeficiency virus pol peptide increases complex stability and in vitro immunogenicity. Proceedings of the National Academy of Sciences of the United States of America 92 (18), 8166–8170 PubMed PMID: 7545295; PubMed Central PMCID: PMC41117.
Pond, S.L., Frost, S.D., 2005. Datamonkey: rapid detection of selective pressure on individual sites of codon alignments. Bioinformatics 21 (10), 2531–2533. https://doi. org/10.1093/bioinformatics/bti320. PubMed PMID: 15713735.
Poon, A.F., Kosakovsky Pond, S.L., Bennett, P., Richman, D.D., Leigh Brown, A.J., Frost, S.D., 2007. Adaptation to human populations is revealed by within-host polymorphisms in HIV-1 and hepatitis C virus. PLoS Pathog. 3 (3), e45. https://doi.org/ 10.1371/journal.ppat.0030045. PubMed PMID: 17397261; PubMed Central PMCID: PMC1839164.
Raveh, B., London, N., Schueler-Furman, O., 2010. Sub-angstrom modeling of complexes between flexible peptides and globular proteins. Proteins 78 (9), 2029–2040. https:// doi.org/10.1002/prot.22716. PubMed PMID: 20455260.
Rolland, M., Carlson, J.M., Manocheewa, S., Swain, J.V., Lanxon-Cookson, E., Deng, W., et al., 2010. Amino-acid co-variation in HIV-1 Gag subtype C: HLA-mediated selection pressure and compensatory dynamics. PLoS One 5 (9). https://doi.org/10.1371/ journal.pone.0012463. PubMed PMID: 20824187; PubMed Central PMCID: PMC2931691.
Sacha, J.B., Chung, C., Rakasz, E.G., Spencer, S.P., Jonas, A.K., Bean, A.T., et al., 2007. Gag-specific CD8+ T lymphocytes recognize infected cells before AIDS-virus integration and viral protein expression. J. Immunol. 178 (5), 2746–2754 (PubMed PMID: 17312117).
Schmitz, J.E., Kuroda, M.J., Santra, S., Sasseville, V.G., Simon, M.A., Lifton, M.A., et al., 1999. Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 283 (5403), 857–860 PubMed PMID: 9933172.
Shafer, R.W., Schapiro, J.M., 2008. HIV-1 drug resistance mutations: an updated framework for the second decade of HAART. AIDS Rev. 10 (2), 67–84 (PubMed PMID: 18615118).
Shen, Y., Maupetit, J., Derreumaux, P., Tuffery, P., 2014. Improved PEP-FOLD approach for peptide and Miniprotein structure prediction. J. Chem. Theory Comput. 10 (10), 4745–4758. https://doi.org/10.1021/ct500592m. PubMed PMID: 26588162.
Smidt, W., 2013. Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. PLoS One 8 (8), e71888. https://doi. org/10.1371/journal.pone.0071888. PubMed PMID: 24015196; PubMed Central PMCID: PMC3756051.
Snoeck J, Fellay J, Bartha I, Douek DC, Telenti A. Mapping of positive selection sites in the HIV-1 genome in the context of RNA and protein structural constraints. Retrovirology (2011) 8:87. doi: https://doi.org/10.1186/1742-4690-8-87. PubMed PMID: 22044801; PubMed Central PMCID: PMC3229471.
Sundaramurthi, J.C., Swaminathan, S., Hanna, L.E., 2012. Resistance-associated epitopes of HIV-1C-highly probable candidates for a multi-epitope vaccine. Immunogenetics 64 (10), 767–772. https://doi.org/10.1007/s00251-012-0635-z. PubMed PMID: 22810271.
Tenzer, S., Wee, E., Burgevin, A., Stewart-Jones, G., Friis, L., Lamberth, K., et al., 2009. Antigen processing influences HIV-specific cytotoxic T lymphocyte immunodominance. Nat. Immunol. 10 (6), 636–646. https://doi.org/10.1038/ni.1728. PubMed PMID: 19412183.
Trott, O., Olson, A.J., 2010. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. Journal of Computational Chemistry 31 (2), 455–461. https://doi.org/10.1002/jcc.21334. PubMed PMID: 19499576.
Tynan, F.E., Borg, N.A., Miles, J.J., Beddoe, T., El-Hassen, D., Silins, S.L., et al., 2005.High resolution structures of highly bulged viral epitopes bound to major histocompatibility complex class I. Implications for T-cell receptor engagement and T-cell immunodominance. J. Biol. Chem. 280 (25), 23900–23909. https://doi.org/10. 1074/jbc.M503060200. PubMed PMID: 15849183.
UNAIDS, 2017. HIV/AIDS World Epidemiology. [cited 2017 March 7th]. Available from: http://aidsinfo.unaids.org/.
Walker, B., McMichael, A., 2012. The T-cell response to HIV. Cold Spring Harbor Perspectives in Medicine 2 (11). https://doi.org/10.1101/cshperspect.a007054. (PubMed PMID: 23002014; PubMed Central PMCID: PMC3543107).
Wang, Y.E., Li, B., Carlson, J.M., Streeck, H., Gladden, A.D., Goodman, R., et al., 2009. Protective HLA class I alleles that restrict acute-phase CD8+ T-cell responses are associated with viral escape mutations located in highly conserved regions of human immunodeficiency virus type 1. J. Virol. 83 (4), 1845–1855. https://doi.org/10. 1128/jvi.01061-08. PubMed PMID: 19036810.
World Health Organization, 2015. The top 10 causes of death. [cited 2017 March 7th]. Available from: http://www.who.int/mediacentre/factsheets/fs310/en/index1.html.
World Health Organization, 2016. Global Health Observatory Data - HIV/AIDS. cited 2017 March 7th. Available from: http://www.who.int/gho/hiv/en/.
Yoshida, I., Sugiura, W., Shibata, J., Ren, F., Yang, Z., Tanaka, H., 2011. Change of positive selection pressure on HIV-1 envelope gene inferred by early and recent samples. PLoS One 6 (4), e18630. https://doi.org/10.1371/journal.pone.0018630. PubMed PMID: 21526184; PubMed Central PMCID: PMC3079721.
Zarling, A.L., Lee, D.R., 1998. Conversion of a human immunodeficiency virus cytotoxic T lymphocyte epitope into a high affinity HLA-Cw3 ligand. Hum. Immunol. 59 (8), 472–482 PubMed PMID: 9712350.
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spelling Arcia, DavidOchoa, RodrigoHernández López, Juan CarlosÁlvarez, Cristiam M.Diaz, Francisco Javier Velilla Hernandez, Paula AndreaAcevedo Sáenz, Liliana692020-01-15T18:59:59Z2020-01-15T18:59:59Z2022-06-302019-041567-134810.1016/j.meegid.2018.07.001https://hdl.handle.net/20.500.12494/15939Arcia, D., Ochoa, R., Hernández, J. C., Álvarez, C. M., Díaz, F. J., Velilla, P. A. y Acevedo Sáenz, L. (2018). Potential immune escape mutations under inferred selection pressure in HIV-1 strains circulating in Medellín, Colombia. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 69: 267-278. 2019. Recuperado de:The introduction of highly active antiretroviral therapy (HAART) has significantly improved life expectancy of HIV-infected patients; nevertheless, it does not eliminate the virus from hosts, so a cure for this infection is crucial. Some strategies have employed the induction of anti-HIV CD8+ T cells. However, the high genetic variability of HIV-1 represents the biggest obstacle for these strategies, since immune escape mutations within epitopes restricted by Human Leukocyte Antigen class I molecules (HLA-I) abrogate the antiviral activity of these cells. We used a bioinformatics pipeline for the determination of such mutations, based on selection pressure and docking/refinement analyses. Fifty HIV-1 infected patients were recruited; HLA-A and HLA-B alleles were typified using sequence-specific oligonucleotide approach, and viral RNA was extracted for the amplification of HIV-1 gag, which was bulk sequenced and aligned to perform selection pressure analysis, using Single Likelihood Ancestor Counting (SLAC) and Fast Unconstrained Bayesian Approximation (FUBAR) algorithms. Positively selected sites were mapped into HLA-I-specific epitopes, and both mutated and wild type epitopes were modelled using PEP-FOLD. Molecular docking and refinement assays were carried out using AutoDock Vina 4 and FlexPepDock. Five positively selected sites were found: S54 at HLA-A*02 GC9, T84 at HLA-A*02 SL9, S125 at HLA-B*35 HY9, S173 at HLA-A*02/B*57 KS12 and I223 at HLA-B*35 HA9. Although some mutations have been previously described as immune escape mutations, the majority of them have not been reported. Molecular docking/refinement analysis showed that one combination of mutations at GC9, one at SL9, and eight at HY9 epitopes could act as immune escape mutations. Moreover, HLA-A*02-positive patients harbouring mutations at KS12, and HLA-B*35-positive patients with mutations at HY9 have significantly higher plasma viral loads than patients lacking such mutations. Thus, HLA-A and -B alleles could be shaping the genetic diversity of HIV-1 through the selection of potential immune escape mutations.https://scienti.colciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000283088http://orcid.org/0000-0002-9200-5698https://scienti.colciencias.gov.co/gruplac/jsp/visualiza/visualizagr.jsp?nro=00000000011355juanc.hernandezl@campusucc.edu.co267-278Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Medicina, Medellín y EnvigadoMedicinaMedellínhttps://www.sciencedirect.com/science/article/abs/pii/S1567134818304714?via%3DihubInfection, Genetics and EvolutionAbram, M.E., Ferris, A.L., Shao, W., Alvord, W.G., Hughes, S.H., 2010. Nature, position, and frequency of mutations made in a single cycle of HIV-1 replication. J. Virol. 84 (19), 9864–9878. https://doi.org/10.1128/jvi.00915-10. PubMed PMID: 20660205.Acevedo-Saenz, L., Ochoa, R., Rugeles, M.T., Olaya-Garcia, P., Velilla-Hernandez, P.A., Diaz, F.J., 2015. Selection pressure in CD8(+) T-cell epitopes in the pol gene of HIV- 1 infected individuals in Colombia. A bioinformatic approach. Viruses 7 (3), 1313–1331. https://doi.org/10.3390/v7031313. PubMed PMID: 25803098Ahlers, J.D., Belyakov, I.M., Thomas, E.K., Berzofsky, J.A., 2001. High-affinity T helper epitope induces complementary helper and APC polarization, increased CTL, and protection against viral infection. J. Clin. Invest. 108 (11), 1677–1685. https://doi. org/10.1172/JCI13463. PubMed PMID: 11733563; PubMed Central PMCID: PMC200990.Ammaranond, P., van Bockel, D.J., Petoumenos, K., McMurchie, M., Finlayson, R., Middleton, M.G., et al., 2011. HIV immune escape at an immunodominant epitope in HLA-B*27-positive individuals predicts viral load outcome. J. Immunol. 186 (1), 479–488. https://doi.org/10.4049/jimmunol.0903227. PubMed PMID: 21115730.Arcia, D., Acevedo-Saenz, L., Rugeles, M.T., Velilla, P.A., 2017. Role of CD8+ T cells in the selection of HIV-1 immune escape mutations. Viral Immunol. 30 (1), 3–12. https://doi.org/10.1089/vim.2016.0095. (PubMed PMID: 27805477).Arts, E.J., Hazuda, D.J., 2012. HIV-1 antiretroviral drug therapy. Cold Spring Harbor Perspectives in Medicine 2 (4), a007161. https://doi.org/10.1101/cshperspect. a007161. PubMed PMID: 22474613.Bennett, M.S., Joseph, A., Ng, H.L., Goldstein, H., Yang, O.O., 2010. Fine-tuning of T-cell receptor avidity to increase HIV epitope variant recognition by cytotoxic T lymphocytes. AIDS 24 (17), 2619–2628. https://doi.org/10.1097/QAD. 0b013e32833f7b22. (PubMed PMID: 20881472; PubMed Central PMCID: PMC2997528).Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., et al., 2000. The Protein Data Bank. Nucleic Acids Res. 28 (1), 235–242 (PubMed PMID: 10592235; PubMed Central PMCID: PMCPMC102472).Borrow, P., Lewicki, H., Hahn, B.H., Shaw, G.M., Oldstone, M.B., 1994. Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection. J Virol 68 (9), 6103–6110 PubMed PMID: 8057491; PubMed Central PMCID: PMC237022.Brumme, Z.L., Brumme, C.J., Heckerman, D., Korber, B.T., Daniels, M., Carlson, J., et al.,2007. Evidence of differential HLA class I-mediated viral evolution in functional and accessory/regulatory genes of HIV-1. PLoS Pathog. 3 (7), e94. https://doi.org/10. 1371/journal.ppat.0030094. PubMed PMID: 17616974; PubMed Central PMCID: PMC1904471.Brumme, Z.L., Tao, I., Szeto, S., Brumme, C.J., Carlson, J.M., Chan, D., et al., 2008. Human leukocyte antigen-specific polymorphisms in HIV-1 Gag and their association with viral load in chronic untreated infection. AIDS 22 (11), 1277–1286. https://doi. org/10.1097/QAD.0b013e3283021a8c. PubMed PMID: 18580606.Cao, J., McNevin, J., Malhotra, U., McElrath, M.J., 2003. Evolution of CD8+ T cell immunity and viral escape following acute HIV-1 infection. J. Immunol. 171 (7), 3837–3846 PubMed PMID: 14500685.Carlson, J.M., Le, A.Q., Shahid, A., Brumme, Z.L., 2015. HIV-1 adaptation to HLA: a window into virus-host immune interactions. Trends Microbiol. 23 (4), 212–224. https://doi.org/10.1016/j.tim.2014.12.008. PubMed PMID: 25613992.Crawford, H., Lumm, W., Leslie, A., Schaefer, M., Boeras, D., Prado, J.G., et al., 2009. Evolution of HLA-B*5703 HIV-1 escape mutations in HLA-B*5703-positive individuals and their transmission recipients. J. Exp. Med. 206 (4), 909–921. https:// doi.org/10.1084/jem.20081984. PubMed PMID: 19307327.Davenport, M.P., Loh, L., Petravic, J., Kent, S.J., 2008. Rates of HIV immune escape and reversion: implications for vaccination. Trends Microbiol. 16 (12), 561–566. https:// doi.org/10.1016/j.tim.2008.09.001. PubMed PMID: 18964018.Duda, A., Lee-Turner, L., Fox, J., Robinson, N., Dustan, S., Kaye, S., et al., 2009. HLAassociated clinical progression correlates with epitope reversion rates in early human immunodeficiency virus infection. J. Virol. 83 (3), 1228–1239. https://doi.org/10. 1128/jvi.01545-08. PubMed PMID: 19019964.Eriksson, E.M., Liegler, T., Keh, C.E., Karlsson, A.C., Holditch, S.J., Pilcher, C.D., et al., 2014. Newly exerted T cell pressures on mutated epitopes following transmission help maintain consensus HIV-1 sequences. PLoS One 10 (4), e0120787. https://doi. org/10.1371/journal.pone.0120787. PubMed PMID: 25919393; PubMed Central PMCID: PMC4412704.Feeney, M.E., Tang, Y., Roosevelt, K.A., Leslie, A.J., McIntosh, K., Karthas, N., et al., 2004. Immune escape precedes breakthrough human immunodeficiency virus type 1 viremia and broadening of the cytotoxic T-lymphocyte response in an HLA-B27-positive long-term-nonprogressing child. J. Virol. 78 (16), 8927–8930. https://doi.org/10. 1128/jvi.78.16.8927-8930.2004. PubMed PMID: 15280502.Ferrari, G., Korber, B., Goonetilleke, N., Liu, M.K., Turnbull, E.L., Salazar-Gonzalez, J.F., et al., 2011. Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection. PLoS Pathog. 7 (2), e1001273. https://doi.org/10.1371/journal.ppat.1001273. PubMed PMID: 21347345.Gijsbers, E.F., van Nuenen, A.C., de la Pena, A.T., Bowles, E.J., Stewart-Jones, G.B., Schuitemaker, H., et al., 2014. Low level of HIV-1 evolution after transmission from mother to child. Sci. Rep. 4, 5079. https://doi.org/10.1038/srep05079. PubMed PMID: 24866155.Goulder, P., Price, D., Nowak, M., Rowland-Jones, S., Phillips, R., McMichael, A., 1997a. Co-evolution of human immunodeficiency virus and cytotoxic T-lymphocyte responses. Immunol. Rev. 159, 17–29 PubMed PMID: 9416500.Goulder, P.J., Sewell, A.K., Lalloo, D.G., Price, D.A., Whelan, J.A., Evans, J., et al., 1997b. Patterns of immunodominance in HIV-1-specific cytotoxic T lymphocyte responses in two human histocompatibility leukocyte antigens (HLA)-identical siblings with HLAA* 0201 are influenced by epitope mutation. J. Exp. Med. 185 (8), 1423–1433 PubMed PMID: 9126923; PubMed Central PMCID: PMC2196285.Goulder, P.J., Brander, C., Tang, Y., Tremblay, C., Colbert, R.A., Addo, M.M., et al., 2001. Evolution and transmission of stable CTL escape mutations in HIV infection. Nature 412 (6844), 334–338. https://doi.org/10.1038/35085576. PubMed PMID: 11460164.HIV Molecular Immunology 2009. http://www.hiv.lanl.gov/content/immunology: Los Alamos National Laboratory, Theoretical Biology and Biophysics, Los Alamos, New Mexico (2009).Jamieson, B.D., Yang, O.O., Hultin, L., Hausner, M.A., Hultin, P., Matud, J., et al., 2003. Epitope escape mutation and decay of human immunodeficiency virus type 1-specific CTL responses. J. Immunol. 171 (10), 5372–5379 PubMed PMID: 14607940.Jin, X., Bauer, D.E., Tuttleton, S.E., Lewin, S., Gettie, A., Blanchard, J., et al., 1999. Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian immunodeficiency virus-infected macaques. J. Exp. Med. 189 (6), 991–998 PubMed PMID: 10075982.Jones, N.A., Wei, X., Flower, D.R., Wong, M., Michor, F., Saag, M.S., et al., 2004. Determinants of human immunodeficiency virus type 1 escape from the primary CD8+ cytotoxic T lymphocyte response. J. Exp. Med. 200 (10), 1243–1256. https:// doi.org/10.1084/jem.20040511. PubMed PMID: 15545352; PubMed Central PMCID: PMC2211924.Kawashima, Y., Pfafferott, K., Frater, J., Matthews, P., Payne, R., Addo, M., et al., 2009. Adaptation of HIV-1 to human leukocyte antigen class I. Nature 458 (7238), 641–645. https://doi.org/10.1038/nature07746. PubMed PMID: 19242411.Kearney, M., Maldarelli, F., Shao, W., Margolick, J.B., Daar, E.S., Mellors, J.W., et al., 2009. Human immunodeficiency virus type 1 population genetics and adaptation in newly infected individuals. J. Virol. 83 (6), 2715–2727. https://doi.org/10.1128/ JVI.01960-08. PubMed PMID: 19116249; PubMed Central PMCID: PMC2648286.Kosakovsky Pond, S.L., Frost, S.D., 2005. Not so different after all: a comparison of methods for detecting amino acid sites under selection. Mol. Biol. Evol. 22 (5), 1208–1222. https://doi.org/10.1093/molbev/msi105. PubMed PMID: 15703242.Koup, R.A., Safrit, J.T., Cao, Y., Andrews, C.A., McLeod, G., Borkowsky, W., et al., 1994. Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J. Virol. 68 (7), 4650–4655 (PubMed PMID: 8207839).Kumar, S., Stecher, G., Tamura, K., 2016. MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol. Biol. Evol. 33 (7), 1870–1874. https:// doi.org/10.1093/molbev/msw054. (PubMed PMID: 27004904).Leslie, A.J., Pfafferott, K.J., Chetty, P., Draenert, R., Addo, M.M., Feeney, M., et al., 2004. HIV evolution: CTL escape mutation and reversion after transmission. Nat. Med. 10 (3), 282–289. https://doi.org/10.1038/nm992. PubMed PMID: 14770175.Leslie, A., Price, D.A., Mkhize, P., Bishop, K., Rathod, A., Day, C., et al., 2006. Differential selection pressure exerted on HIV by CTL targeting identical epitopes but restricted by distinct HLA alleles from the same HLA supertype. J. Immunol. 177 (7), 4699–4708 PubMed PMID: 16982909.Llano A, Williams A, Overa A, Silva-Arrieta S, Brander C. HIV molecular immunology 2013. Yusim K, Korber B, Brander C, Barouch D, de Boer R, Haynes B, et al., Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM. LA-UR 13–27758 (2013).Maartens, G., Celum, C., Lewin, S.R., 2014. HIV infection: epidemiology, pathogenesis, treatment, and prevention. Lancet 384 (9939), 258–271. https://doi.org/10.1016/ s0140-6736(14)60164-1. (PubMed PMID: 24907868).Martinez-Hackert, E., Anikeeva, N., Kalams, S.A., Walker, B.D., Hendrickson, W.A., Sykulev, Y., 2006. Structural basis for degenerate recognition of natural HIV peptide variants by cytotoxic lymphocytes. J. Biol. Chem. 281 (29), 20205–20212. https:// doi.org/10.1074/jbc.M601934200. PubMed PMID: 16702212.Mata-Munguia, C., Escoto-Delgadillo, M., Torres-Mendoza, B., Flores-Soto, M., Vazquez- Torres, M., Galvez-Gastelum, F., et al., 2014. Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. BMC Bioinformatics 15, 72. https://doi.org/10.1186/1471-2105-15-72. PubMed PMID: 24629078; PubMed Central PMCID: PMCPMC4003850.Matsumura, M., Fremont, D.H., Peterson, P.A., Wilson, I.A., 1992. Emerging principles for the recognition of peptide antigens by MHC class I molecules. Science 257 (5072), 927–934 PubMed PMID: 1323878.Guía de práctica clínica basada en la evidencia científica para la atención de la infección por VIH/Sida en adolescentes (con 13 años de edad o más) y adultos. Ministerio de Salud y Protección Social.Moir, S., Chun, T.W., Fauci, A.S., 2011. Pathogenic mechanisms of HIV disease. Annu. Rev. Pathol. 6, 223–248. https://doi.org/10.1146/annurev-pathol-011110-130254. PubMed PMID: 21034222.Moore, C.B., John, M., James, I.R., Christiansen, F.T., Witt, C.S., Mallal, S.A., 2002. Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level. Science 296 (5572), 1439–1443. https://doi.org/10.1126/science.1069660. PubMed PMID: 12029127.Murrell, B., Moola, S., Mabona, A., Weighill, T., Sheward, D., Kosakovsky Pond, S.L., et al., 2013. FUBAR: a fast, unconstrained bayesian approximation for inferring selection. Mol. Biol. Evol. 30 (5), 1196–1205. https://doi.org/10.1093/molbev/ mst030. PubMed PMID: 23420840.Nadai, Y., Eyzaguirre, L.M., Constantine, N.T., Sill, A.M., Cleghorn, F., Blattner, W.A., et al., 2008. Protocol for nearly full-length sequencing of HIV-1 RNA from plasma. PLoS One 3 (1), e1420. https://doi.org/10.1371/journal.pone.0001420. (PubMed PMID: 18183300).Navis, M., Matas, D.E., Rachinger, A., Koning, F.A., van Swieten, P., Kootstra, N.A., et al., 2008. Molecular evolution of human immunodeficiency virus type 1 upon transmission between human leukocyte antigen disparate donor-recipient pairs. PLoS One 3 (6), e2422. https://doi.org/10.1371/journal.pone.0002422. PubMed PMID: 18560583; PubMed Central PMCID: PMC2409968.Novitsky, V., Wang, R., Margolin, L., Baca, J., Moyo, S., Musonda, R., et al., 2010. Dynamics and timing of in vivo mutations at Gag residue 242 during primary HIV-1 subtype C infection. Virology 403 (1), 37–46. https://doi.org/10.1016/j.virol.2010. 04.001. PubMed PMID: 20444482; PubMed Central PMCID: PMC2884147.O'Brien, S.J., Gao, X., Carrington, M., 2001. HLA and AIDS: a cautionary tale. Trends Mol. Med. 7 (9), 379–381 PubMed PMID: 11530315.Pogue, R.R., Eron, J., Frelinger, J.A., Matsui, M., 1995. Amino-terminal alteration of the HLA-A*0201-restricted human immunodeficiency virus pol peptide increases complex stability and in vitro immunogenicity. Proceedings of the National Academy of Sciences of the United States of America 92 (18), 8166–8170 PubMed PMID: 7545295; PubMed Central PMCID: PMC41117.Pond, S.L., Frost, S.D., 2005. Datamonkey: rapid detection of selective pressure on individual sites of codon alignments. Bioinformatics 21 (10), 2531–2533. https://doi. org/10.1093/bioinformatics/bti320. PubMed PMID: 15713735.Poon, A.F., Kosakovsky Pond, S.L., Bennett, P., Richman, D.D., Leigh Brown, A.J., Frost, S.D., 2007. Adaptation to human populations is revealed by within-host polymorphisms in HIV-1 and hepatitis C virus. PLoS Pathog. 3 (3), e45. https://doi.org/ 10.1371/journal.ppat.0030045. PubMed PMID: 17397261; PubMed Central PMCID: PMC1839164.Raveh, B., London, N., Schueler-Furman, O., 2010. Sub-angstrom modeling of complexes between flexible peptides and globular proteins. Proteins 78 (9), 2029–2040. https:// doi.org/10.1002/prot.22716. PubMed PMID: 20455260.Rolland, M., Carlson, J.M., Manocheewa, S., Swain, J.V., Lanxon-Cookson, E., Deng, W., et al., 2010. Amino-acid co-variation in HIV-1 Gag subtype C: HLA-mediated selection pressure and compensatory dynamics. PLoS One 5 (9). https://doi.org/10.1371/ journal.pone.0012463. PubMed PMID: 20824187; PubMed Central PMCID: PMC2931691.Sacha, J.B., Chung, C., Rakasz, E.G., Spencer, S.P., Jonas, A.K., Bean, A.T., et al., 2007. Gag-specific CD8+ T lymphocytes recognize infected cells before AIDS-virus integration and viral protein expression. J. Immunol. 178 (5), 2746–2754 (PubMed PMID: 17312117).Schmitz, J.E., Kuroda, M.J., Santra, S., Sasseville, V.G., Simon, M.A., Lifton, M.A., et al., 1999. Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 283 (5403), 857–860 PubMed PMID: 9933172.Shafer, R.W., Schapiro, J.M., 2008. HIV-1 drug resistance mutations: an updated framework for the second decade of HAART. AIDS Rev. 10 (2), 67–84 (PubMed PMID: 18615118).Shen, Y., Maupetit, J., Derreumaux, P., Tuffery, P., 2014. Improved PEP-FOLD approach for peptide and Miniprotein structure prediction. J. Chem. Theory Comput. 10 (10), 4745–4758. https://doi.org/10.1021/ct500592m. PubMed PMID: 26588162.Smidt, W., 2013. Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M. PLoS One 8 (8), e71888. https://doi. org/10.1371/journal.pone.0071888. PubMed PMID: 24015196; PubMed Central PMCID: PMC3756051.Snoeck J, Fellay J, Bartha I, Douek DC, Telenti A. Mapping of positive selection sites in the HIV-1 genome in the context of RNA and protein structural constraints. Retrovirology (2011) 8:87. doi: https://doi.org/10.1186/1742-4690-8-87. PubMed PMID: 22044801; PubMed Central PMCID: PMC3229471.Sundaramurthi, J.C., Swaminathan, S., Hanna, L.E., 2012. Resistance-associated epitopes of HIV-1C-highly probable candidates for a multi-epitope vaccine. Immunogenetics 64 (10), 767–772. https://doi.org/10.1007/s00251-012-0635-z. PubMed PMID: 22810271.Tenzer, S., Wee, E., Burgevin, A., Stewart-Jones, G., Friis, L., Lamberth, K., et al., 2009. Antigen processing influences HIV-specific cytotoxic T lymphocyte immunodominance. Nat. Immunol. 10 (6), 636–646. https://doi.org/10.1038/ni.1728. PubMed PMID: 19412183.Trott, O., Olson, A.J., 2010. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. Journal of Computational Chemistry 31 (2), 455–461. https://doi.org/10.1002/jcc.21334. PubMed PMID: 19499576.Tynan, F.E., Borg, N.A., Miles, J.J., Beddoe, T., El-Hassen, D., Silins, S.L., et al., 2005.High resolution structures of highly bulged viral epitopes bound to major histocompatibility complex class I. Implications for T-cell receptor engagement and T-cell immunodominance. J. Biol. Chem. 280 (25), 23900–23909. https://doi.org/10. 1074/jbc.M503060200. PubMed PMID: 15849183.UNAIDS, 2017. HIV/AIDS World Epidemiology. [cited 2017 March 7th]. Available from: http://aidsinfo.unaids.org/.Walker, B., McMichael, A., 2012. The T-cell response to HIV. Cold Spring Harbor Perspectives in Medicine 2 (11). https://doi.org/10.1101/cshperspect.a007054. (PubMed PMID: 23002014; PubMed Central PMCID: PMC3543107).Wang, Y.E., Li, B., Carlson, J.M., Streeck, H., Gladden, A.D., Goodman, R., et al., 2009. Protective HLA class I alleles that restrict acute-phase CD8+ T-cell responses are associated with viral escape mutations located in highly conserved regions of human immunodeficiency virus type 1. J. Virol. 83 (4), 1845–1855. https://doi.org/10. 1128/jvi.01061-08. PubMed PMID: 19036810.World Health Organization, 2015. The top 10 causes of death. [cited 2017 March 7th]. Available from: http://www.who.int/mediacentre/factsheets/fs310/en/index1.html.World Health Organization, 2016. Global Health Observatory Data - HIV/AIDS. cited 2017 March 7th. Available from: http://www.who.int/gho/hiv/en/.Yoshida, I., Sugiura, W., Shibata, J., Ren, F., Yang, Z., Tanaka, H., 2011. Change of positive selection pressure on HIV-1 envelope gene inferred by early and recent samples. PLoS One 6 (4), e18630. https://doi.org/10.1371/journal.pone.0018630. PubMed PMID: 21526184; PubMed Central PMCID: PMC3079721.Zarling, A.L., Lee, D.R., 1998. Conversion of a human immunodeficiency virus cytotoxic T lymphocyte epitope into a high affinity HLA-Cw3 ligand. Hum. 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