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https://repositorio.ufba.br/handle/ri/15535
metadata.dc.type: | Artigo de Periódico |
Título : | Simultaneous RNA quantification of human and retroviral genomes reveals intact interferon signaling in HTLV-1-infected CD4+ T cell lines |
Otros títulos : | Virology Journal |
Autor : | Moens, Britta Pannecouque, Christophe López, Giovanni Talledo, Michael Gotuzzo, Eduardo Cunha, Antônio Ricardo Khouri Bittencourt, Achilea Candida Lisboa Farré, Lourdes Castro, Bernardo Galvão Vandamme, Anne Mieke Van Weyenbergh, Johan |
metadata.dc.creator: | Moens, Britta Pannecouque, Christophe López, Giovanni Talledo, Michael Gotuzzo, Eduardo Cunha, Antônio Ricardo Khouri Bittencourt, Achilea Candida Lisboa Farré, Lourdes Castro, Bernardo Galvão Vandamme, Anne Mieke Van Weyenbergh, Johan |
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. |
Palabras clave : | Retrovirus IFN-α HIV-1 HTLV-1 IFN-α signaling Antiviral activity |
metadata.dc.rights: | Acesso Aberto |
URI : | http://repositorio.ufba.br/ri/handle/ri/15535 |
Fecha de publicación : | 2012 |
Aparece en las colecciones: | Artigo Publicado em Periódico (Faculdade de Medicina) |
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