Expression of the interleukin-18 gene from rhesus macaque by the simian immunodeficiency virus does not result in increased viral replication.
Interleukin-18 (IL-18), previously known as interferon-gamma (IFN-gamma)-inducing factor (IGIF), is a proinflammatory cytokine expressed by activated macrophages that acts in synergy with IL-12 as an important amplifying factor for IFN-gamma production and Th1 development. To study the effect of IL-18 on a lentiviral infection, we cloned the IL-18 gene from a rhesus macaque and constructed replication-competent simian immunodeficiency virus (SIV) that expressed either the precursor pro-IL-18 (SIV(IL-18)) or the mature form (SIV(mIL-18)) of IL-18. The predicted amino acid sequence for rhesus IL-18 had 96% homology with the human one, differing in only 8 of 193 residues. SIV(IL-18) and SIV(mIL-18) replicated more slowly than control viruses in the CEM x 174 cell line and resulted in the development of chronically infected cell lines that expressed high levels of infectious SIV. The cell line generated by SIV(IL-18) released large quantities of IL-18 into the supernatant, whereas the one obtained from SIV(mIL-18) showed the accumulation of IL-18 in the cytoplasm. Similarly, SIV(IL-18) and SIV(mIL-18) replicated more slowly than the unmodified viral vector in rhesus peripheral blood mononuclear cells (PMBC), but only SIV(IL-18) expressed biologically active IL-18. These experiments show that the precursor form of IL-18 is necessary for the efficient release of the cytokine and that IL-18 does not promote increased replication of SIV in rhesus PBMC.
Giavedoni
L D
LD
Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78245-0549, USA. Lgiavedo@icarus.sfbr.org
Imhoof
J D
JD
Velasquillo
M C
MC
Parodi
L M
LM
Hodara
V L
VL
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020382:Interleukin-18 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000821:virology; D008253:Macaca mulatta / Q000235:genetics / Q000821:virology; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication
D020382:Interleukin-18; D007371:Interferon-gamma