Article
Simultaneous RNA quantification of human and retroviral genomes reveals intact interferon signaling in HTLV-1-infected CD4+ T cell lines.
Registro en:
MOENS, B. et al. Simultaneous RNA quantification of human and retroviral genomes reveals intact interferon signaling in HTLV-1-infected CD4+ T cell lines. Virology Journal, v. 9, p. 171, 2012.
1743-422X
10.1186/1743-422X-9-171
Autor
Moens, Britta
Pannecouque, Christophe
López, Giovanni
Talledo, Michael
Gotuzzo, Eduardo
Cunha, Antonio Ricardo Khouri
Bittencourt, Achilea Candida Lisboa
Vallve, Maria de Lourdes Farre
Castro Filho, Bernardo Galvão
Vandamme, Anne-Mieke
Van Weyenbergh, Johan Jozef Rosa Maria
Resumen
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.