Mathematical Modeling of Ultradeep Sequencing Data Reveals that Acute CD8+ T-Lymphocyte Responses Exert Strong Selective Pressure in Simian Immunodeficiency Virus-Infected Macaques but Still Fail To Clear Founder Epitope Sequences

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Published in:	Journal of Virology Vol. 84; no. 11; pp. 5802 - 5814
Main Authors:	Love, Tanzy M T, Thurston, Sally W, Keefer, Michael C, Dewhurst, Stephen, Lee, Ha Youn
Format:	Journal Article
Language:	English
Published:	United States American Society for Microbiology 01-06-2010 American Society for Microbiology (ASM)
Subjects:	Amino Acid Sequence Animals Antibodies, Viral Antigens, Viral CD8-Positive T-Lymphocytes - immunology Epitopes Founder Effect Human immunodeficiency virus 1 Immune Evasion - immunology Immunity, Cellular Macaca Models, Immunological Models, Theoretical Pathogenesis and Immunity Simian Acquired Immunodeficiency Syndrome - immunology Simian immunodeficiency virus Simian Immunodeficiency Virus - immunology
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Abstract	Article Usage Stats Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue JVI About JVI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy JVI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0022-538X Online ISSN: 1098-5514 Copyright © 2014 by the American Society for Microbiology. For an alternate route to JVI .asm.org, visit: JVI
AbstractList	The prominent role of antiviral cytotoxic CD8+ T-lymphocytes (CD8-TL) in containing the acute viremia of human and simian immunodeficiency viruses (HIV-1 and SIV) has rationalized the development of T-cell-based vaccines. However, the presence of escape mutations in the acute stage of infection has raised a concern that accelerated escape from vaccine-induced CD8-TL responses might undermine vaccine efficacy. We reanalyzed previously published data of 101,822 viral genomes of three CD8-TL epitopes, Nef103-111RM9 (RM9), Tat28-35SL8 (SL8), and Gag181-189CM9 (CM9), sampled by ultradeep pyrosequencing from eight macaques. Multiple epitope variants appeared during the resolution of acute viremia, followed by the predominance of a single mutant epitope. By fitting a mathematical model, we estimated the first acute escape rate as 0.36 day-1 within escape-prone epitopes, RM9 and SL8, and the chronic escape rate as 0.014 day-1 within the CM9 epitope. Our estimate of SIV acute escape rates was found to be comparable to very early HIV-1 escape rates. The timing of the first escape was more highly correlated with the timing of the peak CD8-TL response than with the magnitude of the CD8-TL response. The transmitted epitope decayed more than 400 times faster during the acute viral decline stage than predicted by a neutral evolution model. However, the founder epitope persisted as a minor population even at the viral set point; in contrast, the majority of acute escape epitopes were completely cleared. Our results suggest that a reservoir of SIV infection is preferentially formed by virus with the transmitted epitope. ABSTRACT The prominent role of antiviral cytotoxic CD8 + T-lymphocytes (CD8-TL) in containing the acute viremia of human and simian immunodeficiency viruses (HIV-1 and SIV) has rationalized the development of T-cell-based vaccines. However, the presence of escape mutations in the acute stage of infection has raised a concern that accelerated escape from vaccine-induced CD8-TL responses might undermine vaccine efficacy. We reanalyzed previously published data of 101,822 viral genomes of three CD8-TL epitopes, Nef 103-111 RM9 (RM9), Tat 28-35 SL8 (SL8), and Gag 181-189 CM9 (CM9), sampled by ultradeep pyrosequencing from eight macaques. Multiple epitope variants appeared during the resolution of acute viremia, followed by the predominance of a single mutant epitope. By fitting a mathematical model, we estimated the first acute escape rate as 0.36 day −1 within escape-prone epitopes, RM9 and SL8, and the chronic escape rate as 0.014 day −1 within the CM9 epitope. Our estimate of SIV acute escape rates was found to be comparable to very early HIV-1 escape rates. The timing of the first escape was more highly correlated with the timing of the peak CD8-TL response than with the magnitude of the CD8-TL response. The transmitted epitope decayed more than 400 times faster during the acute viral decline stage than predicted by a neutral evolution model. However, the founder epitope persisted as a minor population even at the viral set point; in contrast, the majority of acute escape epitopes were completely cleared. Our results suggest that a reservoir of SIV infection is preferentially formed by virus with the transmitted epitope. The prominent role of antiviral cytotoxic CD8 + T-lymphocytes (CD8-TL) in containing the acute viremia of human and simian immunodeficiency viruses (HIV-1 and SIV) has rationalized the development of T-cell-based vaccines. However, the presence of escape mutations in the acute stage of infection has raised a concern that accelerated escape from vaccine-induced CD8-TL responses might undermine vaccine efficacy. We reanalyzed previously published data of 101,822 viral genomes of three CD8-TL epitopes, Nef 103-111 RM9 (RM9), Tat 28-35 SL8 (SL8), and Gag 181-189 CM9 (CM9), sampled by ultradeep pyrosequencing from eight macaques. Multiple epitope variants appeared during the resolution of acute viremia, followed by the predominance of a single mutant epitope. By fitting a mathematical model, we estimated the first acute escape rate as 0.36 day −1 within escape-prone epitopes, RM9 and SL8, and the chronic escape rate as 0.014 day −1 within the CM9 epitope. Our estimate of SIV acute escape rates was found to be comparable to very early HIV-1 escape rates. The timing of the first escape was more highly correlated with the timing of the peak CD8-TL response than with the magnitude of the CD8-TL response. The transmitted epitope decayed more than 400 times faster during the acute viral decline stage than predicted by a neutral evolution model. However, the founder epitope persisted as a minor population even at the viral set point; in contrast, the majority of acute escape epitopes were completely cleared. Our results suggest that a reservoir of SIV infection is preferentially formed by virus with the transmitted epitope. Article Usage Stats Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue JVI About JVI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy JVI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0022-538X Online ISSN: 1098-5514 Copyright © 2014 by the American Society for Microbiology. For an alternate route to JVI .asm.org, visit: JVI The prominent role of antiviral cytotoxic CD8(+) T-lymphocytes (CD8-TL) in containing the acute viremia of human and simian immunodeficiency viruses (HIV-1 and SIV) has rationalized the development of T-cell-based vaccines. However, the presence of escape mutations in the acute stage of infection has raised a concern that accelerated escape from vaccine-induced CD8-TL responses might undermine vaccine efficacy. We reanalyzed previously published data of 101,822 viral genomes of three CD8-TL epitopes, Nef(103-111)RM9 (RM9), Tat(28-35)SL8 (SL8), and Gag(181-189)CM9 (CM9), sampled by ultradeep pyrosequencing from eight macaques. Multiple epitope variants appeared during the resolution of acute viremia, followed by the predominance of a single mutant epitope. By fitting a mathematical model, we estimated the first acute escape rate as 0.36 day(-1) within escape-prone epitopes, RM9 and SL8, and the chronic escape rate as 0.014 day(-1) within the CM9 epitope. Our estimate of SIV acute escape rates was found to be comparable to very early HIV-1 escape rates. The timing of the first escape was more highly correlated with the timing of the peak CD8-TL response than with the magnitude of the CD8-TL response. The transmitted epitope decayed more than 400 times faster during the acute viral decline stage than predicted by a neutral evolution model. However, the founder epitope persisted as a minor population even at the viral set point; in contrast, the majority of acute escape epitopes were completely cleared. Our results suggest that a reservoir of SIV infection is preferentially formed by virus with the transmitted epitope.
Author	Stephen Dewhurst Michael C. Keefer Tanzy M. T. Love Sally W. Thurston Ha Youn Lee
AuthorAffiliation	Department of Biostatistics and Computational Biology, University of Rochester, Rochester, New York 14642, 1 Department of Medicine, University of Rochester, Rochester, New York 14642, 2 Department of Microbiology and Immunology, University of Rochester, Rochester, New York 14642 3
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Cites_doi	10.1128/JVI.77.24.13348-13360.2003 10.1016/j.meegid.2010.02.001 10.4049/jimmunol.171.10.5372 10.1371/journal.ppat.1000378 10.1073/pnas.94.5.1890 10.1371/journal.ppat.0040012 10.1128/JVI.78.5.2581-2585.2004 10.1126/science.281.5375.363 10.1186/1742-4690-6-57 10.1128/JVI.78.5.2187-2200.2004 10.1128/JVI.01277-07 10.1128/JVI.02132-08 10.1084/jem.20090365 10.1006/jtbi.2000.1076 10.1128/JVI.02660-07 10.1073/pnas.0802203105 10.1016/j.jbiotec.2008.03.021 10.1126/science.271.5255.1582 10.1097/00002030-200002180-00003 10.1084/jem.20082831 10.1128/JVI.00946-07 10.1128/JCM.43.1.406-413.2005 10.1038/nprot.2006.442 10.1128/JVI.02568-08 10.1038/35030124 10.1080/0266476042000214501 10.1126/science.286.5443.1353 10.1128/JVI.01061-08 10.1038/nm998 10.1128/jvi.68.7.4650-4655.1994 10.1128/jvi.68.4.2362-2370.1994 10.1073/pnas.0700666104 10.1126/science.283.5403.857 10.1038/nm0502-493 10.1016/j.jtbi.2009.07.038 10.1371/journal.pbio.0040090 10.1128/JVI.77.8.4911-4927.2003 10.1086/526786 10.1128/JVI.79.9.5721-5731.2005 10.1097/00002030-200309050-00005 10.1084/jem.20090378 10.1128/JVI.02176-07 10.1002/j.1538-7305.1951.tb01366.x 10.1128/JVI.77.8.5037-5038.2003 10.1371/journal.pcbi.0020024 10.1084/jem.189.6.991 10.1371/journal.pone.0000321 10.1038/nm992 10.1128/JVI.77.3.2081-2092.2003 10.1128/JVI.00199-09 10.1128/jvi.68.9.6103-6110.1994 10.1128/JVI.00897-09 10.1128/jvi.69.8.5087-5094.1995 10.1128/JVI.00465-07 10.1073/pnas.190065897
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References	15827187 - J Virol. 2005 May;79(9):5721-31 15635002 - J Clin Microbiol. 2005 Jan;43(1):406-13 14966520 - Nat Med. 2004 Mar;10(3):275-81 12663814 - J Virol. 2003 Apr;77(8):5037-8 14770175 - Nat Med. 2004 Mar;10(3):282-9 17389912 - PLoS One. 2007;2(3):e321 19360124 - PLoS Pathog. 2009 Apr;5(4):e1000378 18353945 - J Virol. 2008 Jun;82(11):5398-407 19487424 - J Exp Med. 2009 Jun 8;206(6):1273-89 12960819 - AIDS. 2003 Sep 5;17(13):1871-9 19193811 - J Virol. 2009 Apr;83(8):3556-67 19535437 - J Virol. 2009 Sep;83(17):8470-81 17406511 - Nat Protoc. 2006;1(6):2573-82 18256145 - J Virol. 2008 Apr;82(8):3952-70 12663797 - J Virol. 2003 Apr;77(8):4911-27 14963115 - J Virol. 2004 Mar;78(5):2187-200 19414559 - J Exp Med. 2009 May 11;206(5):1117-34 16515366 - PLoS Biol. 2006 Apr;4(4):e90 14645590 - J Virol. 2003 Dec;77(24):13348-60 19515775 - J Virol. 2009 Aug;83(16):8247-53 18616967 - J Biotechnol. 2008 Aug 31;136(1-2):3-10 15905727 - J Acquir Immune Defic Syndr. 2005 Jun 1;39(2):133-7 14963161 - J Virol. 2004 Mar;78(5):2581-5 8057491 - J Virol. 1994 Sep;68(9):6103-10 17699572 - J Virol. 2007 Nov;81(21):11982-91 16604188 - PLoS Comput Biol. 2006 Mar;2(3):e24 18490657 - Proc Natl Acad Sci U S A. 2008 May 27;105(21):7552-7 7541846 - J Virol. 1995 Aug;69(8):5087-94 12525643 - J Virol. 2003 Feb;77(3):2081-92 17404226 - Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6365-70 10558989 - Science. 1999 Nov 12;286(5443):1353-7 20149896 - Infect Genet Evol. 2010 May;10(4):555-60 11984594 - Nat Med. 2002 May;8(5):493-9 9705713 - Science. 1998 Jul 17;281(5375):363, 365 19339351 - J Virol. 2009 Jun;83(12):6011-9 18225952 - PLoS Pathog. 2008 Jan;4(1):e12 10716497 - AIDS. 2000 Feb 18;14(3):225-33 8207839 - J Virol. 1994 Jul;68(7):4650-5 19660475 - J Theor Biol. 2009 Nov 21;261(2):341-60 10716909 - J Theor Biol. 2000 Apr 7;203(3):285-301 10995459 - Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10966-71 11014195 - Nature. 2000 Sep 21;407(6802):386-90 8139022 - J Virol. 1994 Apr;68(4):2362-70 9933172 - Science. 1999 Feb 5;283(5403):857-60 8599114 - Science. 1996 Mar 15;271(5255):1582-6 17728222 - J Virol. 2007 Nov;81(22):12179-88 18275276 - J Infect Dis. 2008 Feb 15;197(4):563-71 19487423 - J Exp Med. 2009 Jun 8;206(6):1253-72 19505314 - Retrovirology. 2009;6:57 19036810 - J Virol. 2009 Feb;83(4):1845-55 17507468 - J Virol. 2007 Aug;81(15):8346-51 10075982 - J Exp Med. 1999 Mar 15;189(6):991-8 14607940 - J Immunol. 2003 Nov 15;171(10):5372-9 9050875 - Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1890-5 e_1_3_2_26_2 e_1_3_2_49_2 e_1_3_2_28_2 e_1_3_2_41_2 e_1_3_2_20_2 e_1_3_2_43_2 e_1_3_2_22_2 e_1_3_2_45_2 e_1_3_2_24_2 e_1_3_2_47_2 e_1_3_2_9_2 e_1_3_2_16_2 e_1_3_2_37_2 e_1_3_2_7_2 e_1_3_2_18_2 e_1_3_2_39_2 e_1_3_2_54_2 e_1_3_2_10_2 e_1_3_2_31_2 e_1_3_2_52_2 e_1_3_2_5_2 e_1_3_2_12_2 e_1_3_2_33_2 e_1_3_2_58_2 e_1_3_2_3_2 e_1_3_2_14_2 e_1_3_2_35_2 e_1_3_2_56_2 (e_1_3_2_19_2) 2005; 39 e_1_3_2_50_2 e_1_3_2_27_2 e_1_3_2_48_2 e_1_3_2_29_2 e_1_3_2_40_2 e_1_3_2_21_2 e_1_3_2_42_2 e_1_3_2_23_2 e_1_3_2_44_2 e_1_3_2_25_2 e_1_3_2_46_2 e_1_3_2_15_2 e_1_3_2_38_2 e_1_3_2_8_2 e_1_3_2_17_2 e_1_3_2_59_2 e_1_3_2_6_2 e_1_3_2_30_2 e_1_3_2_53_2 e_1_3_2_32_2 e_1_3_2_51_2 e_1_3_2_11_2 e_1_3_2_34_2 e_1_3_2_57_2 e_1_3_2_4_2 e_1_3_2_13_2 e_1_3_2_36_2 e_1_3_2_55_2 e_1_3_2_2_2
References_xml	– ident: e_1_3_2_55_2 doi: 10.1128/JVI.77.24.13348-13360.2003 – ident: e_1_3_2_27_2 doi: 10.1016/j.meegid.2010.02.001 – ident: e_1_3_2_28_2 doi: 10.4049/jimmunol.171.10.5372 – volume: 39 start-page: 133 year: 2005 ident: e_1_3_2_19_2 publication-title: J. Acquir. Immune. Defic. Syndr. – ident: e_1_3_2_38_2 doi: 10.1371/journal.ppat.1000378 – ident: e_1_3_2_47_2 doi: 10.1073/pnas.94.5.1890 – ident: e_1_3_2_37_2 doi: 10.1371/journal.ppat.0040012 – ident: e_1_3_2_23_2 doi: 10.1128/JVI.78.5.2581-2585.2004 – ident: e_1_3_2_49_2 doi: 10.1126/science.281.5375.363 – ident: e_1_3_2_10_2 doi: 10.1186/1742-4690-6-57 – ident: e_1_3_2_21_2 doi: 10.1128/JVI.78.5.2187-2200.2004 – ident: e_1_3_2_36_2 doi: 10.1128/JVI.01277-07 – ident: e_1_3_2_5_2 – ident: e_1_3_2_2_2 doi: 10.1128/JVI.02132-08 – ident: e_1_3_2_25_2 doi: 10.1084/jem.20090365 – ident: e_1_3_2_54_2 doi: 10.1006/jtbi.2000.1076 – ident: e_1_3_2_50_2 doi: 10.1128/JVI.02660-07 – ident: e_1_3_2_30_2 doi: 10.1073/pnas.0802203105 – ident: e_1_3_2_15_2 doi: 10.1016/j.jbiotec.2008.03.021 – ident: e_1_3_2_44_2 doi: 10.1126/science.271.5255.1582 – ident: e_1_3_2_58_2 doi: 10.1097/00002030-200002180-00003 – ident: e_1_3_2_31_2 doi: 10.1084/jem.20082831 – ident: e_1_3_2_39_2 doi: 10.1128/JVI.00946-07 – ident: e_1_3_2_43_2 doi: 10.1128/JCM.43.1.406-413.2005 – ident: e_1_3_2_33_2 doi: 10.1038/nprot.2006.442 – ident: e_1_3_2_12_2 doi: 10.1128/JVI.02568-08 – ident: e_1_3_2_6_2 doi: 10.1038/35030124 – ident: e_1_3_2_18_2 doi: 10.1080/0266476042000214501 – ident: e_1_3_2_59_2 doi: 10.1126/science.286.5443.1353 – ident: e_1_3_2_56_2 doi: 10.1128/JVI.01061-08 – ident: e_1_3_2_22_2 doi: 10.1038/nm998 – ident: e_1_3_2_32_2 doi: 10.1128/jvi.68.7.4650-4655.1994 – ident: e_1_3_2_48_2 doi: 10.1128/jvi.68.4.2362-2370.1994 – ident: e_1_3_2_8_2 doi: 10.1073/pnas.0700666104 – ident: e_1_3_2_52_2 doi: 10.1126/science.283.5403.857 – ident: e_1_3_2_46_2 – ident: e_1_3_2_42_2 doi: 10.1038/nm0502-493 – ident: e_1_3_2_34_2 doi: 10.1016/j.jtbi.2009.07.038 – ident: e_1_3_2_7_2 doi: 10.1371/journal.pbio.0040090 – ident: e_1_3_2_57_2 doi: 10.1128/JVI.77.8.4911-4927.2003 – ident: e_1_3_2_45_2 doi: 10.1086/526786 – ident: e_1_3_2_17_2 doi: 10.1128/JVI.79.9.5721-5731.2005 – ident: e_1_3_2_20_2 doi: 10.1097/00002030-200309050-00005 – ident: e_1_3_2_51_2 doi: 10.1084/jem.20090378 – ident: e_1_3_2_16_2 doi: 10.1128/JVI.02176-07 – ident: e_1_3_2_53_2 doi: 10.1002/j.1538-7305.1951.tb01366.x – ident: e_1_3_2_41_2 doi: 10.1128/JVI.77.8.5037-5038.2003 – ident: e_1_3_2_24_2 doi: 10.1371/journal.pcbi.0020024 – ident: e_1_3_2_29_2 doi: 10.1084/jem.189.6.991 – ident: e_1_3_2_3_2 doi: 10.1371/journal.pone.0000321 – ident: e_1_3_2_35_2 doi: 10.1038/nm992 – ident: e_1_3_2_4_2 doi: 10.1128/JVI.77.3.2081-2092.2003 – ident: e_1_3_2_13_2 doi: 10.1128/JVI.00199-09 – ident: e_1_3_2_11_2 doi: 10.1128/jvi.68.9.6103-6110.1994 – ident: e_1_3_2_9_2 doi: 10.1128/JVI.00897-09 – ident: e_1_3_2_40_2 doi: 10.1128/jvi.69.8.5087-5094.1995 – ident: e_1_3_2_14_2 doi: 10.1128/JVI.00465-07 – ident: e_1_3_2_26_2 doi: 10.1073/pnas.190065897
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Snippet	Article Usage Stats Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley... The prominent role of antiviral cytotoxic CD8(+) T-lymphocytes (CD8-TL) in containing the acute viremia of human and simian immunodeficiency viruses (HIV-1 and... ABSTRACT The prominent role of antiviral cytotoxic CD8 + T-lymphocytes (CD8-TL) in containing the acute viremia of human and simian immunodeficiency viruses... The prominent role of antiviral cytotoxic CD8+ T-lymphocytes (CD8-TL) in containing the acute viremia of human and simian immunodeficiency viruses (HIV-1 and... The prominent role of antiviral cytotoxic CD8 + T-lymphocytes (CD8-TL) in containing the acute viremia of human and simian immunodeficiency viruses (HIV-1 and...
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SubjectTerms	Amino Acid Sequence Animals Antibodies, Viral Antigens, Viral CD8-Positive T-Lymphocytes - immunology Epitopes Founder Effect Human immunodeficiency virus 1 Immune Evasion - immunology Immunity, Cellular Macaca Models, Immunological Models, Theoretical Pathogenesis and Immunity Simian Acquired Immunodeficiency Syndrome - immunology Simian immunodeficiency virus Simian Immunodeficiency Virus - immunology
Title	Mathematical Modeling of Ultradeep Sequencing Data Reveals that Acute CD8+ T-Lymphocyte Responses Exert Strong Selective Pressure in Simian Immunodeficiency Virus-Infected Macaques but Still Fail To Clear Founder Epitope Sequences
URI	http://jvi.asm.org/content/84/11/5802.abstract https://www.ncbi.nlm.nih.gov/pubmed/20335256 https://search.proquest.com/docview/733182086 https://search.proquest.com/docview/746163160 https://pubmed.ncbi.nlm.nih.gov/PMC2876615
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