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Journal of Virology, March 2005, p. 2900-2909, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.2900-2909.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Cellular and Humoral Immunity following Snow Mountain Virus Challenge

Lisa Lindesmith,1 Christine Moe,2 Jacques LePendu,3 Jeffrey A. Frelinger,4 John Treanor,5 and Ralph S. Baric1,4*

Department of Epidemiology,1 Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina,4 Department of International Health, Emory University, Atlanta, Georgia,2 Institute of Biology, Nantes, France,3 Department of Medicine, University of Rochester, Rochester, New York5

Received 29 July 2004/ Accepted 12 October 2004

Little is known about the immune response to noroviruses. To elucidate the immunobiology of norovirus infection in humans, 15 volunteers were challenged with Snow Mountain virus (SMV), a genogroup 2 norovirus. We assessed the cellular and humoral immune response and infection by analyzing stool, serum, saliva, and peripheral blood mononuclear cell (PBMC) responses pre- and postchallenge. In contrast to Norwalk virus (NV), SMV infection was not dependent upon blood group secretor status. Nine of 15 volunteers were infected and showed a ≥4-fold increase over the prechallenge anti-SMV serum immunoglobulin G (IgG) titer, mostly subclass IgG1. Although serum IgG elicited by SMV infection was cross-reactive with Hawaii virus (HV), another genogroup 2 norovirus, salivary IgA was less cross-reactive. Neither SMV-elicited serum IgG nor salivary IgA cross-reacted with NV, a genogroup 1 norovirus. Significant increases in serum gamma interferon (IFN-{gamma}) and IL-2, but not IL-6 or IL-10, were noted on day 2 postchallenge. For the majority of volunteers, both infected and uninfected, PBMCs stimulated with norovirus virus-like particles secreted IFN-{gamma} and other Th1 cytokines, suggesting previous norovirus exposure in most volunteers. Like the IgG antibodies, the SMV-activated T cells were cross-reactive with HV but not NV. IFN-{gamma} production was dependent upon CD4+ cells, consistent with a predominant, but not exclusive, Th1 response. To our knowledge, this is the first report characterizing T-cell and cytokine responses following live norovirus challenge.

* Corresponding author. Mailing address: 2103 McGavran-Greenberg HA, CB7435, School of Public Health, University of North Carolina—Chapel Hill, Chapel Hill, NC 27599. Phone: (919) 966-3895. Fax: (919) 966-2089. E-mail: rbaric{at}sph.unc.edu.

Journal of Virology, March 2005, p. 2900-2909, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.2900-2909.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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