TY - JOUR
T1 - Inhibition of HIV-1 in the central nervous system by IFN-α2 delivered by an SV40 vector
AU - Cordelier, Pierre
AU - Calarota, Sandra A.
AU - Pomerantz, Roger J.
AU - Xiaoshan, Jiang
AU - Strayer, David S.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - In human immunodeficiency virus type 1 (HIV-1)-infected individuals, virus-induced production of interferon-α (IFN-α) is impaired. In order to obtain regulated expression of IFN-α that responds to HIV-1 infection, a recombinant SV40 vector was designed that carries the human IFN-α2 cDNA under the control of the HIV-1 long terminal repeat (LTR) (SV[HIVLTR]IFN). Thus, the IFN-α2 gene would be trans-activated on infection with HIV-1. This vector was tested to determine if central nervous system (CNS) cell types that may be potential HIV-1 targets could be transduced and protected from HIV. SV[HIVLTR]IFN transduced NT2 cells, a human neuronal precursor cell line, mature neurons derived from NT2 precursor cells, and human primary monocyte-derived macrophages. IFN-α2 expression was retained in mature neurons after SV[HIVLTR]IFN-transduced NT2 precursor cells were induced to differentiate using retinoic acid. IFN-α expression was detected only after exposing transduced cells to HIV. Furthermore, SV[HIVLTR]IFN-delivered IFN-α2 expression significantly inhibited replication of multiple strains of HIV in both NT2 and NT2-derived mature neurons. SV[HIVLTR]IFN transduction also inhibited HIV-1BaL replication in human primary monocyte-derived macrophages. Therefore, we have demonstrated the effectiveness of IFN-α2, delivered by an SV40 vector driven by HIV-1 LTR as a promoter, to protect several CNS-based, potentially HIV-susceptible cell types. These findings may have implications for therapy of HIV-1 infection in the CNS.
AB - In human immunodeficiency virus type 1 (HIV-1)-infected individuals, virus-induced production of interferon-α (IFN-α) is impaired. In order to obtain regulated expression of IFN-α that responds to HIV-1 infection, a recombinant SV40 vector was designed that carries the human IFN-α2 cDNA under the control of the HIV-1 long terminal repeat (LTR) (SV[HIVLTR]IFN). Thus, the IFN-α2 gene would be trans-activated on infection with HIV-1. This vector was tested to determine if central nervous system (CNS) cell types that may be potential HIV-1 targets could be transduced and protected from HIV. SV[HIVLTR]IFN transduced NT2 cells, a human neuronal precursor cell line, mature neurons derived from NT2 precursor cells, and human primary monocyte-derived macrophages. IFN-α2 expression was retained in mature neurons after SV[HIVLTR]IFN-transduced NT2 precursor cells were induced to differentiate using retinoic acid. IFN-α expression was detected only after exposing transduced cells to HIV. Furthermore, SV[HIVLTR]IFN-delivered IFN-α2 expression significantly inhibited replication of multiple strains of HIV in both NT2 and NT2-derived mature neurons. SV[HIVLTR]IFN transduction also inhibited HIV-1BaL replication in human primary monocyte-derived macrophages. Therefore, we have demonstrated the effectiveness of IFN-α2, delivered by an SV40 vector driven by HIV-1 LTR as a promoter, to protect several CNS-based, potentially HIV-susceptible cell types. These findings may have implications for therapy of HIV-1 infection in the CNS.
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U2 - 10.1089/10799900360708605
DO - 10.1089/10799900360708605
M3 - Article
C2 - 14565857
AN - SCOPUS:0141742138
VL - 23
SP - 477
EP - 488
JO - Journal of Interferon and Cytokine Research
JF - Journal of Interferon and Cytokine Research
SN - 1079-9907
IS - 9
ER -