Comparative assessment of virulence of recombinant vaccinia viruses expressing IL-2 and IL-15 in immunodeficient mice

Citation
Lp. Perera et al., Comparative assessment of virulence of recombinant vaccinia viruses expressing IL-2 and IL-15 in immunodeficient mice, P NAS US, 98(9), 2001, pp. 5146-5151
Citations number
36
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN journal
0027-8424 → ACNP
Volume
98
Issue
9
Year of publication
2001
Pages
5146 - 5151
Database
ISI
SICI code
0027-8424(20010424)98:9<5146:CAOVOR>2.0.ZU;2-7
Abstract
IL-2 and -15 belong to the four cu-helix bundle family of cytokines and dis play a spectrum of overlapping immune functions because of shared signal tr ansducing receptor components of the IL-2 receptor complex. However, recent evidence suggests a nonredundant unique role for IL-15 in the establishmen t and perhaps maintenance of peripheral natural killer (NK) cell population s in vivo. To explore the contribution of locally released IL-15 on periphe ral NK-cell-mediated innate immune responses, we generated a recombinant va ccinia virus that expresses IL-15 and evaluated the course of Vaccinial dis ease in athymic nude mice. Coexpression of IL-15 resulted in the attenuatio n of virulence of vaccinia virus, and mice inoculated with 10(5) plaque-for ming units or less resolved the infection successfully. In contrast, mice i noculated with a similar dose of the control vaccinia virus failed to elimi nate the virus and died of generalized vaccinial disease. Enhanced expressi on of IL-12 and IFN-gamma as well as induction of chemokines were evident i n the mice inoculated with IL-15-expressing vaccinia virus in addition to a n increase in NK cells in the spleen. However. in this model system, the de gree of attenuation in viral virulence attained with coexpression of IL-15 was much less than that achieved with coexpression of IL-2. suggesting that the peripheral NK-cell-mediated events are more responsive to IL-2 than to IL-15.