| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Center for Infectious Disease and Vaccine Research, and
Department of Pediatrics and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655; and
Division of Infectious Diseases, Department of Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131
We report on the role of specific CD8+ T cells in the pathogenesis of a highly lethal human viral disease, hantavirus pulmonary syndrome (HPS). HPS is a zoonotic disease caused by transmission of Sin Nombre virus (SNV) from chronically infected deer mice. In humans, this fulminant infection is characterized by lung capillary leakage, respiratory failure, and cardiogenic shock. Individuals with HLA-B*3501 have an increased risk of developing severe HPS, suggesting that CD8+ T cell responses to SNV contribute to pathogenesis. We identified three CD8+ T cell epitopes in SNV presented by HLA-B*3501 and quantitated circulating SNV-specific CD8+ T cells in 11 acute HPS patients using HLA/peptide tetramers. We found significantly higher frequencies of SNV-specific T cells in patients with severe HPS requiring mechanical ventilation (up to 44.2% of CD8+ T cells) than in moderately ill HPS patients hospitalized but not requiring mechanical ventilation (up to 9.8% of CD8+ T cells). These results imply that virus-specific CD8+ T cells contribute to HPS disease outcome. Intense CD8+ T cell responses to SNV may be induced by the encounter of the unnatural human host to this zoonotic virus without coevolution. This may also be the immunopathologic basis of other life-threatening human virus infections.
This article has been cited by other articles:
|
|
 |
|
  P. Godoy, D. Marsac, E. Stefas, P. Ferrer, N. D. Tischler, K. Pino, P. Ramdohr, P. Vial, P. D. T. Valenzuela, M. Ferres, et al. Andes Virus Antigens Are Shed in Urine of Patients with Acute Hantavirus Cardiopulmonary Syndrome J. Virol., May 15, 2009; 83(10): 5046 - 5055. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A Clay, E. M Lehmer, A. Previtali, S. St. Jeor, and M. D. Dearing Contact heterogeneity in deer mice: implications for Sin Nombre virus transmission Proc R Soc B, April 7, 2009; 276(1660): 1305 - 1312. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Easterbrook and S. L. Klein Corticosteroids modulate Seoul virus infection, regulatory T-cell responses and matrix metalloprotease 9 expression in male, but not female, Norway rats J. Gen. Virol., November 1, 2008; 89(11): 2723 - 2730. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Schountz, J. Prescott, A. C. Cogswell, L. Oko, K. Mirowsky-Garcia, A. P. Galvez, and B. Hjelle Regulatory T cell-like responses in deer mice persistently infected with Sin Nombre virus PNAS, September 25, 2007; 104(39): 15496 - 15501. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Stoltz, C. Ahlm, A. Lundkvist, and J. Klingstrom Lambda Interferon (IFN-{lambda}) in Serum Is Decreased in Hantavirus-Infected Patients, and In Vitro-Established Infection Is Insensitive to Treatment with All IFNs and Inhibits IFN-{gamma}-Induced Nitric Oxide Production J. Virol., August 15, 2007; 81(16): 8685 - 8691. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Tuuminen, E. Kekalainen, S. Makela, I. Ala-Houhala, F. A. Ennis, K. Hedman, J. Mustonen, A. Vaheri, and T. P. Arstila Human CD8+ T Cell Memory Generation in Puumala Hantavirus Infection Occurs after the Acute Phase and Is Associated with Boosting of EBV-Specific CD8+ Memory T Cells J. Immunol., August 1, 2007; 179(3): 1988 - 1995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Klingstrom, J. Hardestam, M. Stoltz, B. Zuber, A. Lundkvist, S. Linder, and C. Ahlm Loss of cell membrane integrity in puumala hantavirus-infected patients correlates with levels of epithelial cell apoptosis and perforin. J. Virol., August 1, 2006; 80(16): 8279 - 8282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Prescott, C. Ye, G. Sen, and B. Hjelle Induction of Innate Immune Response Genes by Sin Nombre Hantavirus Does Not Require Viral Replication J. Virol., December 15, 2005; 79(24): 15007 - 15015. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Muranyi, U. Bahr, M. Zeier, and F. J. van der Woude Hantavirus Infection J. Am. Soc. Nephrol., December 1, 2005; 16(12): 3669 - 3679. [Full Text] [PDF]
|
|
|
|
|
|
K. Maeda, K. West, T. Toyosaki-Maeda, A. L. Rothman, F. A. Ennis, and M. Terajima Identification and analysis for cross-reactivity among hantaviruses of H-2b-restricted cytotoxic T-lymphocyte epitopes in Sin Nombre virus nucleocapsid protein J. Gen. Virol., July 1, 2004; 85(7): 1909 - 1919. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
