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

Britta Moens1, Christophe Pannecouque2, Giovanni López3, Michael Talledo3, Eduardo Gotuzzo34, Ricardo Khouri15, Achiléa Bittencourt6, Lourdes Farré5, Bernardo Galvão-Castro57, Anne-Mieke Vandamme18 and Johan Van Weyenbergh159*

Author Affiliations

1 Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, K.U.Leuven, Leuven, Belgium

2 Laboratory for Virology and Chemotherapy, Rega Institute for Medical Research, K.U.Leuven, Leuven, Belgium

3 Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, 31, Peru

4 Departamento de Medicina, Facultad de Medicina, Universidad Peruana Cayetano Heredia, Lima, Peru

5 Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (FIOCRUZ), Salvador-Bahia, Brazil

6 Department of Pathology, Professor Edgar Santos Teaching Hospital, Federal University of Bahia, Salvador-Bahia, Brazil

7 Bahia School of Medicine and Public Health, Salvador-Bahia, Brazil

8 Centro de Malária e outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal

9 Institute for Immunological Investigation iii-INCT, Sao Paulo, Brazil

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Virology Journal 2012, 9:171  doi:10.1186/1743-422X-9-171

Published: 23 August 2012

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.

Keywords:
Retrovirus; IFN-α; HIV-1; HTLV-1; IFN-α signaling; Antiviral activity