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Journal of Virology, August 2000, p. 7196-7203, Vol. 74, No. 16
Laboratory of Immunovirology, Pediatric
Research Center and Department of Microbiology and Immunology,
University of Montreal and Sainte-Justine Hospital, Montreal, Quebec,
Canada H3T 1C5
Received 24 March 2000/Accepted 15 May 2000
Infections with herpes simplex virus type 1 (HSV-1) in humans and
in animal models are accompanied by enhanced natural killer (NK)
activity. In vitro, HSV-1 also enhances the NK activity of human
peripheral blood mononuclear cells (PBMC). The molecular basis of this
enhanced NK activity, however, is not well characterized. We
investigated the role of human interleukin-15 (IL-15) in this phenomenon and report here that HSV-1-mediated enhanced NK activity was
abrogated by neutralizing antibodies for IL-15 but not for other
cytokines (i.e., IL-2, IL-12, gamma interferon [IFN-
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Innate Immune Response of the Human Host to
Exposure with Herpes Simplex Virus Type 1: In Vitro Control of the
Virus Infection by Enhanced Natural Killer Activity via
Interleukin-15 Induction
], tumor
necrosis factor alpha, or IFN-
). Anti-CD122 antibodies which block
signaling through IL-2 receptor
chain, and therefore neutralize the
effects of IL-15 (and IL-2), also abrogated this enhancement.
Furthermore, HSV-1 increased the levels of IL-15 mRNA and the
production of IL-15 in HSV-1-infected PBMC cultures. The neutralization
of IL-15 in cocultures of PBMC with HSV-1-infected cells significantly
increased HSV-1 production. These results strongly suggest a role for
IL-15 in the HSV-1-mediated in vitro enhancement of NK activity and in
the PBMC-mediated suppression of HSV-1 replication.
*
Corresponding author. Mailing address: Laboratory of
Immunovirology, Ste-Justine Hospital, 3175 Côte Ste-Catherine,
Montréal, Québec, Canada H3T 1C5. Phone: (514) 345-4729. Fax: (514) 345-4801. E-mail for Ali Ahmad:
ahmada{at}justine.umontreal.ca. E-mail for José
Menezes: svanasve{at}justine.umontreal.edu.
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