PMID- 11331040 OWN - NLM STAT- MEDLINE DCOM- 20010802 LR - 20151119 IS - 1079-9907 (Print) IS - 1079-9907 (Linking) VI - 21 IP - 3 DP - 2001 Mar TI - Expression of the interleukin-18 gene from rhesus macaque by the simian immunodeficiency virus does not result in increased viral replication. PG - 173-80 AB - 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. FAU - Giavedoni, L D AU - Giavedoni LD AD - Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78245-0549, USA. Lgiavedo@icarus.sfbr.org FAU - Imhoof, J D AU - Imhoof JD FAU - Velasquillo, M C AU - Velasquillo MC FAU - Parodi, L M AU - Parodi LM FAU - Hodara, V L AU - Hodara VL LA - eng SI - GENBANK/AF303732 GR - P51 RR 13986-01/RR/NCRR NIH HHS/United States GR - R01 A141923/PHS HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Interferon Cytokine Res JT - Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research JID - 9507088 RN - 0 (Interleukin-18) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Amino Acid Sequence MH - Animals MH - Cell Line MH - Cloning, Molecular MH - Genetic Vectors/genetics MH - Humans MH - Interferon-gamma/metabolism MH - Interleukin-18/chemistry/genetics/*metabolism MH - Leukocytes, Mononuclear/virology MH - *Macaca mulatta/genetics/virology MH - Molecular Sequence Data MH - Sequence Alignment MH - Simian Immunodeficiency Virus/genetics/*physiology MH - *Virus Replication EDAT- 2001/05/02 10:00 MHDA- 2001/08/03 10:01 CRDT- 2001/05/02 10:00 PHST- 2001/05/02 10:00 [pubmed] PHST- 2001/08/03 10:01 [medline] PHST- 2001/05/02 10:00 [entrez] AID - 10.1089/107999001750133212 [doi] PST - ppublish SO - J Interferon Cytokine Res. 2001 Mar;21(3):173-80. doi: 10.1089/107999001750133212.