The Journal of Experimental Medicine
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Published 2 September 2002. doi:10.1084/jem.20011255
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*Hantavirus Infections
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© Rockefeller University Press, 0022-1007/2002/9/579/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 5, September 2, 2002 579-588
Long-lived Memory T Lymphocyte Responses After Hantavirus Infection

Heather L. Van Epps1, Masanori Terajima1, Jukka Mustonen2, T. Petteri Arstila3, Elizabeth A. Corey1, Antti Vaheri3 and Francis A. Ennis1

1 Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655
2 Medical School, University of Tampere and Tampere University Hospital, FIN-33104 Tampere, Finland
3 Department of Virology and the Department of Immunology, Haartman Institute and Helsinki University Central Hospital, University of Helsinki, FIN-00014 Helsinki, Finland

Address correspondence to Francis A. Ennis, Center for Infectious Disease and Vaccine Research, S5-326, University of Massachusetts Medical School, 55 Lake Ave. North, Worcester, MA 01655. Phone: 508-856-4182; Fax: 508-856-4890. E-mail: Francis.ennis{at}umassmed.edu

Puumala virus (PUUV) is a hantavirus that causes hemorrhagic fever with renal syndrome (HFRS), which is an important public health problem in large parts of Europe. We examined the memory cytolytic T lymphocyte (CTL) responses in 13 Finnish individuals who had HFRS between 1984 and 1995. In seven of these donors, we detected virus-specific CTL responses against the PUUV nucleocapsid (N) protein after in vitro stimulation with PUUV. Six novel CD8+ CTL epitopes were defined on the N protein and were found to be restricted by various HLA alleles including A2, A28, B7, and B8. This is the first demonstration of PUUV-specific CTL responses in humans, and the first identification of CTL epitopes on PUUV. In addition, this study provides one of the few characterizations of a human antiviral memory T cell response, without the complicating issues of virus persistence or reinfection. Interferon (IFN)-{gamma} ELISPOT analysis showed that memory CTL specific for these epitopes were present at high frequency in PUUV-immune individuals many years after acute infection in the absence of detectable viral RNA. The frequencies of PUUV-specific CTL were comparable to or exceeded those found in other viral systems including influenza, EBV and HIV, in which CTL responses may be boosted by periodic reinfection or virus persistence.

Key Words: Puumala virus • hantavirus • immunologic memory • cytotoxic T lymphocytes • T lymphocyte epitopes


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