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Journal of Virology, August 2008, p. 7515-7523, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.00464-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Reovirus Serotypes Elicit Distinctive Patterns of Recall Immunity in Humans

CIHR National Training Program in Allergy and Asthma Research, Departments of Immunology,¹ Medical Microbiology,² Pediatrics/Child Health, University of Manitoba, Winnipeg, Manitoba, Canada³

Received 3 March 2008/ Accepted 19 May 2008

Mammalian orthoreoviruses (reoviruses) are ubiquitous viral agents that infect cells in respiratory and enteric tracts. The frequency and nature of human cellular immunoregulatory responses against reovirus are unknown. Here we establish systems to detect and quantify reovirus-induced cytokine and chemokine recall responses using primary cultures of virus-infected peripheral blood mononuclear cells (PBMC) and two widely used reovirus serotypes, type 1 Lang (T1L) and type 3 Dearing (T3D) reexposure in vitro. In cultures from 44 healthy adults, reovirus induced exceptionally strong CD4 and CD8 T-cell-dependent gamma interferon (IFN-) recall responses concomitant with intense interleukin 10 (IL-10) production. These responses were elicited independently of viral replication. Surprisingly, paired analyses of subject responses to these two common serotypes revealed that while both elicit intense Th1-dominated immunity, median T3D-driven responses were 2.2-fold weaker (P = 0.0004) than those elicited by T1L. Recall responses evoked by these viral serotypes differed markedly in their mechanism of regulation. T3D IL-10 and IFN- responses were CD4 and CD8 dependent and blocked by interfering with CD86 costimulation but were CD80 independent. T1L responses were consistently CD28 and CD80/86 independent. Thus, despite extensive genetic and morphological similarities between reovirus serotypes, the nature and intensity of the human recall responses as well as the control mechanisms regulating them are clearly distinct.

Published ahead of print on 28 May 2008.