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Simultaneous RNA quantification of human and retroviral genomes reveals intact interferon signaling in HTLV-1-infected CD4+ T cell lines.

By Britta Moens, Christophe Pannecouque, Giovanni López, Michael Talledo, Eduardo Gotuzzo, Ricardo Khouri, Achilea Candida Lisboa Bittencourt, Maria de Lourdes Farre Vallve, Bernardo Galvão Castro Filho, Anne-Mieke Vandamme and Johan Van Weyenbergh

Abstract

BACKGROUND: IFN-α contributes extensively to host immune response upon viral infection through antiviral, pro-apoptotic, antiproliferative and immunomodulatory activities. Although extensively documented in various types of human cancers and viral infections, controversy exists in the exact mechanism of action of IFN-α in human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type 1 (HTLV-1) retroviral infections. RESULTS: IFN-α displayed strong anti-HIV-1 effects in HIV-1/HTLV-1 co-infected MT-4 cells in vitro, demonstrated by the dose-dependent inhibition of the HIV-1-induced cytopathic effect (IC50 = 83.5 IU/ml, p < 0.0001) and p24 levels in cell-free supernatant (IC50 = 1.2 IU/ml, p < 0.0001). In contrast, IFN-α treatment did not affect cell viability or HTLV-1 viral mRNA levels in HTLV-1 mono-infected cell lines, based on flow cytometry and nCounter analysis, respectively. However, we were able to confirm the previously described post-transcriptional inhibition of HTLV-1 p19 secretion by IFN-α in cell lines (p = 0.0045), and extend this finding to primary Adult T cell Leukemia patient samples (p = 0.031). In addition, through microarray and nCounter analysis, we performed the first genome-wide simultaneous quantification of complete human and retroviral transciptomes, demonstrating significant transcriptional activation of interferon-stimulated genes without concomitant decrease of HTLV-1 mRNA levels. CONCLUSIONS: Taken together, our results indicate that both the absence of in vitro antiproliferative and pro-apoptotic activity as well as the modest post-transcriptional antiviral activity of IFN-α against HTLV-1, were not due to a cell-intrinsic defect in IFN-α signalisation, but rather represents a retrovirus-specific phenomenon, considering the strong HIV-1 inhibition in co-infected cells

Topics: Retrovirus, IFN-α, HIV-1, HTLV-1, IFN-α signaling, Antiviral activity, Linfócitos T CD4-Positivos/imunologia, Linfócitos T CD4-Positivos/virologia, Vírus 1 Linfotrópico T Humano/imunologia, Interferon-alfa/biossíntese, Transdução de Sinal, Sobrevivência Celular, Perfilação da Expressão Gênica, HIV-1/imunologia, Humanos, RNA/biossíntese, RNA/genética
Publisher: BioMed Central
Year: 2012
OAI identifier: oai:agregador.ibict.br.RI_FIOCRUZ:oai:localhost:icict/8793
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