Universidad Peruana Cayetano Heredia

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

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dc.contributor.author Moens, B.
dc.contributor.author Pannecouque, C.
dc.contributor.author Lápez, G.
dc.contributor.author Talledo Albujar, Michael John
dc.contributor.author Gotuzzo Herencia, José Eduardo
dc.contributor.author Khouri, R.
dc.contributor.author Bittencourt, A.
dc.contributor.author Farré, L.
dc.contributor.author Galvão-Castro, B.
dc.contributor.author Vandamme, A.-M.
dc.contributor.author Van Weyenbergh, J.
dc.date.accessioned 2022-01-18T19:34:36Z
dc.date.available 2022-01-18T19:34:36Z
dc.date.issued 2012
dc.identifier.uri https://hdl.handle.net/20.500.12866/11045
dc.description.abstract Background: IFN- 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- in human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type 1 (HTLV-1) retroviral infections. Results: IFN- 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=83.5IU/ml, p<0.0001) and p24 levels in cell-free supernatant (IC50=1.2IU/ml, p<0.0001). In contrast, IFN- 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- 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- against HTLV-1, were not due to a cell-intrinsic defect in IFN- signalisation, but rather represents a retrovirus-specific phenomenon, considering the strong HIV-1 inhibition in co-infected cells. en_US
dc.language.iso eng
dc.publisher BioMed Central
dc.relation.ispartofseries Virology Journal
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Humans en_US
dc.subject controlled study en_US
dc.subject in vitro study en_US
dc.subject nucleotide sequence en_US
dc.subject RNA en_US
dc.subject flow cytometry en_US
dc.subject Human T cell leukemia virus 1 en_US
dc.subject Human T-lymphotropic virus 1 en_US
dc.subject human cell en_US
dc.subject messenger RNA en_US
dc.subject Signal Transduction en_US
dc.subject protein secretion en_US
dc.subject cell viability en_US
dc.subject concentration response en_US
dc.subject IC 50 en_US
dc.subject HIV-1 en_US
dc.subject virus RNA en_US
dc.subject alpha interferon en_US
dc.subject CD4+ T lymphocyte en_US
dc.subject Gene Expression Profiling en_US
dc.subject HTLV-1 en_US
dc.subject Gag protein en_US
dc.subject Cell Survival en_US
dc.subject CD4-Positive T-Lymphocytes en_US
dc.subject human genome en_US
dc.subject transcriptome en_US
dc.subject Interferon-alpha en_US
dc.subject microarray analysis en_US
dc.subject Human immunodeficiency virus 1 en_US
dc.subject Antiviral activity en_US
dc.subject cell level en_US
dc.subject gene activation en_US
dc.subject IFN- signaling en_US
dc.subject intracellular signaling en_US
dc.subject leukemia cell en_US
dc.subject protein p19 en_US
dc.subject Retrovirus en_US
dc.subject RNA analysis en_US
dc.subject transactivation en_US
dc.subject virus genome en_US
dc.subject virus inhibition en_US
dc.title Simultaneous RNA quantification of human and retroviral genomes reveals intact interferon signaling in HTLV-1-infected CD4+ T cell lines en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1186/1743-422X-9-171
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.02
dc.relation.issn 1743-422X


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