Expression of IL-18 by SIV does not modify the outcome of the antiviral immune response.
Interleukin 18 (IL-18) is a proinflammatory cytokine expressed by several cell types, including activated dendritic cells and macrophages, that acts in synergy with IL-12 as an important amplifying factor for IFN-gamma production and Th1 development. To study the immunological and virological effects of IL-18 expression in the context of a lentiviral infection, we inoculated rhesus macaques with a high dose of replication-competent simian immunodeficiency virus (SIV) vectors carrying the rhesus IL-18 gene in the sense (SIV(IL-18)) or antisense (SIV(FIGI)) orientation. Both vectors behaved as attenuated viruses, resulting in low viral loads, induction of low and transient levels of inflammatory cytokines, no CD4(+) T cell depletion, and mild activation of T lymphocytes. Although IL-18-expressing virus could be isolated from some SIV(IL18)-infected macaques for 12 weeks postinfection, the anti-SIV humoral and cellular immune responses of macaques inoculated with SIV(IL18) and SIV(FIGI) were similar to each other, with the exception of an early IFN-gamma response in animals infected with SIV(IL18). In summary, expression of IL-18 during the acute phase of SIV infection does not increase viral replication or influence the outcome of the antiviral immune response.
Giavedoni
Luis D
LD
Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas 78245-0549, USA. Lgiavedo@icarus.sfbr.org
Velasquillo
M Cristina
MC
Parodi
Laura M
LM
Hubbard
Gene B
GB
Hodara
Vida L
VL
D000818:Animals; D007371:Interferon-gamma / Q000096:biosynthesis; D020382:Interleukin-18 / Q000096:biosynthesis*; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000302:isolation & purification; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D020382:Interleukin-18; D007371:Interferon-gamma