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Journal of Virology, August 2000, p. 7196-7203, Vol. 74, No. 16
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

Ali Ahmad,* Ehsan Sharif-Askari, Lama Fawaz, and José Menezes*

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-gamma ], tumor necrosis factor alpha, or IFN-alpha ). Anti-CD122 antibodies which block signaling through IL-2 receptor beta  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.

Journal of Virology, August 2000, p. 7196-7203, Vol. 74, No. 16
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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