Abstract
Interleukin-18 (IL-18), previously known as interferon-γ (IFN-γ)-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-γ 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 (SIVIL-18) or the mature form (SIVmIL-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. SIVIL-18 and SIVmIL-18 replicated more slowly than control viruses in the CEM × 3174 cell line and resulted in the development of chronically infected cell lines that expressed high levels of infectious SIV. The cell line generated by SIVIL-18 released large quantities of IL-18 into the supernatant, whereas the one obtained from SIVmIL-18 showed the accumulation of IL-18 in the cytoplasm. Similarly, SIVIL-18 and SIVmIL-18 replicated more slowly than the unmodified viral vector in rhesus peripheral blood mononuclear cells (PMBC), but only SIVIL-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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 173-180 |
| Number of pages | 8 |
| Journal | Journal of Interferon and Cytokine Research |
| Volume | 21 |
| Issue number | 3 |
| DOIs | |
| State | Published - 2001 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
- Virology
- Cell Biology
Cite this
Expression of the interleukin-18 gene from rhesus macaque by the simian immunodeficiency virus does not result in increased viral replication. / Giavedoni, L. D.; Imhoof, J. D.; Velasquillo, M. C.; Parodi, L. M.; Hodara, V. L.
In: Journal of Interferon and Cytokine Research, Vol. 21, No. 3, 2001, p. 173-180.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expression of the interleukin-18 gene from rhesus macaque by the simian immunodeficiency virus does not result in increased viral replication
AU - Giavedoni, L. D.
AU - Imhoof, J. D.
AU - Velasquillo, M. C.
AU - Parodi, L. M.
AU - Hodara, V. L.
PY - 2001
Y1 - 2001
N2 - Interleukin-18 (IL-18), previously known as interferon-γ (IFN-γ)-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-γ 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 (SIVIL-18) or the mature form (SIVmIL-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. SIVIL-18 and SIVmIL-18 replicated more slowly than control viruses in the CEM × 3174 cell line and resulted in the development of chronically infected cell lines that expressed high levels of infectious SIV. The cell line generated by SIVIL-18 released large quantities of IL-18 into the supernatant, whereas the one obtained from SIVmIL-18 showed the accumulation of IL-18 in the cytoplasm. Similarly, SIVIL-18 and SIVmIL-18 replicated more slowly than the unmodified viral vector in rhesus peripheral blood mononuclear cells (PMBC), but only SIVIL-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.
AB - Interleukin-18 (IL-18), previously known as interferon-γ (IFN-γ)-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-γ 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 (SIVIL-18) or the mature form (SIVmIL-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. SIVIL-18 and SIVmIL-18 replicated more slowly than control viruses in the CEM × 3174 cell line and resulted in the development of chronically infected cell lines that expressed high levels of infectious SIV. The cell line generated by SIVIL-18 released large quantities of IL-18 into the supernatant, whereas the one obtained from SIVmIL-18 showed the accumulation of IL-18 in the cytoplasm. Similarly, SIVIL-18 and SIVmIL-18 replicated more slowly than the unmodified viral vector in rhesus peripheral blood mononuclear cells (PMBC), but only SIVIL-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.
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U2 - 10.1089/107999001750133212
DO - 10.1089/107999001750133212
M3 - Article
VL - 21
SP - 173
EP - 180
JO - Journal of Interferon and Cytokine Research
JF - Journal of Interferon and Cytokine Research
SN - 1079-9907
IS - 3
ER -