The predictability of virus–host interactions and disease progression in rapidly evolving human viral infections has been difficult to assess because of host and genetic viral diversity. Here we examined adaptive HIV-specific cellular and humoral immune responses and viral evolution in adult monozygotic twins simultaneously infected with the same virus. CD4 T cell counts and viral loads followed similar trajectories over three years of follow up. The initial CD8 T cell response targeted 17 epitopes, 15 of which were identical in each twin, including two immunodominant responses. By 36 months after infection, 14 of 15 initial responses were still detectable in both, whereas all new responses were subdominant and remained so. Of four responses that declined in both twins, three demonstrated mutations at the same residue. In addition, the evolving antibody responses cross-neutralized the other twin's virus, with similar changes in the pattern of evolution in the envelope gene. These results reveal considerable concordance of adaptive cellular and humoral immune responses and HIV evolution in the same genetic environment, suggesting constraints on mutational pathways to HIV immune escape.
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20 March 2006
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March 13 2006
Constraints on HIV-1 evolution and immunodominance revealed in monozygotic adult twins infected with the same virus
Rika Draenert,
Rika Draenert
1Howard Hughes Medical Institute
2Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129
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Todd M. Allen,
Todd M. Allen
1Howard Hughes Medical Institute
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Yang Liu,
Yang Liu
3Monogram Biosciences, South San Francisco, CA 94080
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Terri Wrin,
Terri Wrin
3Monogram Biosciences, South San Francisco, CA 94080
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Colombe Chappey,
Colombe Chappey
3Monogram Biosciences, South San Francisco, CA 94080
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Cori L. Verrill,
Cori L. Verrill
1Howard Hughes Medical Institute
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Guillem Sirera,
Guillem Sirera
4Fundació irsiCaixa, Hospital Universitari Germans Trias i Pujol, Badalona, Spain 08916
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Robert L. Eldridge,
Robert L. Eldridge
1Howard Hughes Medical Institute
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Matthew P. Lahaie,
Matthew P. Lahaie
1Howard Hughes Medical Institute
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Lidia Ruiz,
Lidia Ruiz
4Fundació irsiCaixa, Hospital Universitari Germans Trias i Pujol, Badalona, Spain 08916
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Bonaventura Clotet,
Bonaventura Clotet
4Fundació irsiCaixa, Hospital Universitari Germans Trias i Pujol, Badalona, Spain 08916
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Christos J. Petropoulos,
Christos J. Petropoulos
3Monogram Biosciences, South San Francisco, CA 94080
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Bruce D. Walker,
Bruce D. Walker
1Howard Hughes Medical Institute
2Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129
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Javier Martinez-Picado
Javier Martinez-Picado
4Fundació irsiCaixa, Hospital Universitari Germans Trias i Pujol, Badalona, Spain 08916
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Rika Draenert
1Howard Hughes Medical Institute
2Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129
Todd M. Allen
1Howard Hughes Medical Institute
Yang Liu
3Monogram Biosciences, South San Francisco, CA 94080
Terri Wrin
3Monogram Biosciences, South San Francisco, CA 94080
Colombe Chappey
3Monogram Biosciences, South San Francisco, CA 94080
Cori L. Verrill
1Howard Hughes Medical Institute
Guillem Sirera
4Fundació irsiCaixa, Hospital Universitari Germans Trias i Pujol, Badalona, Spain 08916
Robert L. Eldridge
1Howard Hughes Medical Institute
Matthew P. Lahaie
1Howard Hughes Medical Institute
Lidia Ruiz
4Fundació irsiCaixa, Hospital Universitari Germans Trias i Pujol, Badalona, Spain 08916
Bonaventura Clotet
4Fundació irsiCaixa, Hospital Universitari Germans Trias i Pujol, Badalona, Spain 08916
Christos J. Petropoulos
3Monogram Biosciences, South San Francisco, CA 94080
Bruce D. Walker
1Howard Hughes Medical Institute
2Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129
Javier Martinez-Picado
4Fundació irsiCaixa, Hospital Universitari Germans Trias i Pujol, Badalona, Spain 08916
CORRESPONDENCE Bruce D. Walker: [email protected] OR Javier Martinez-Picado: [email protected]
Abbreviations used: BLCL, B lymphoblastoid cell line; SFC, spot-forming cell.
Received:
October 20 2005
Accepted:
February 15 2006
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2006
J Exp Med (2006) 203 (3): 529–539.
Article history
Received:
October 20 2005
Accepted:
February 15 2006
Connected Content
Citation
Rika Draenert, Todd M. Allen, Yang Liu, Terri Wrin, Colombe Chappey, Cori L. Verrill, Guillem Sirera, Robert L. Eldridge, Matthew P. Lahaie, Lidia Ruiz, Bonaventura Clotet, Christos J. Petropoulos, Bruce D. Walker, Javier Martinez-Picado; Constraints on HIV-1 evolution and immunodominance revealed in monozygotic adult twins infected with the same virus . J Exp Med 20 March 2006; 203 (3): 529–539. doi: https://doi.org/10.1084/jem.20052116
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