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Interferon lambda inhibits dengue virus replication in epithelial cells.

Palma-Ocampo HK, Flores-Alonso JC, Vallejo-Ruiz V, Reyes-Leyva J, Flores-Mendoza L, Herrera-Camacho I, Rosas-Murrieta NH, Santos-López G - Virol. J. (2015)

Bottom Line: We found increased (~1.8 times) serological IFN-λ in dengue fever patients compared to healthy blood donors.The reduction of viral titer corresponded with increased ISG mRNA levels (MX1 and OAS1), with the highest inhibition occurring at ISG's peak expression.Mechanisms for the cellular and organismal interplay between DENV and IFN- λ need to be further studied as they could provide insights into strategies to treat this disease.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio de Biología Molecular y Virología, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Metepec, Puebla, México. hk.palma@gmail.com.

ABSTRACT

Background: In viral disease, infection is controlled at the cellular level by type I interferon (IFN-I), but dengue virus (DENV) has the ability to inhibit this response. Type III interferon, also known as lambda IFN (IFN-III or IFN-λ), is a complementary pathway to the antiviral response by IFN-I. This work analyzed the IFN-λ (IFN-III) mediated antiviral response against DENV serotype 2 (DENV-2) infection.

Methods: Dengue fever patients were sampled to determine their IFN-λ levels by ELISA. To study the IFN-λ response during DENV infection we selected the epithelial cell line C33-A, and we demonstrated that it is permissive to DENV-2 infection. The effect of IFN-λ on virus replication was determined in these cells, in parallel to the expression of IFN-stimulated genes (ISGs), and Suppressor of Cytokine Signaling (SOCS), genes measured by RT-qPCR.

Results: We found increased (~1.8 times) serological IFN-λ in dengue fever patients compared to healthy blood donors. IFN-λ inhibited DENV-2 replication in a dose-dependent manner in vitro. The reduction of viral titer corresponded with increased ISG mRNA levels (MX1 and OAS1), with the highest inhibition occurring at ISG's peak expression. Presence of IFN-negative regulators, SOCS1 and SOCS3, during DENV-2 infection was associated with reduced IFN-λ1 expression.

Conclusions: Evidence described here suggests that IFN-λ is a good candidate inhibitor of viral replication in dengue infection. Mechanisms for the cellular and organismal interplay between DENV and IFN- λ need to be further studied as they could provide insights into strategies to treat this disease. Furthermore, we report a novel epithelial model to study dengue infection in vitro.

No MeSH data available.


Related in: MedlinePlus

Increase in SOCS1 coincides with a fall in IFN-λ1 transcription. The same values used in the graphs of Fig. 8 were re-plotted and sorted according to experimental condition: (a) mock-infected cells, (b) infected with DENV-2 (MOI = 0.1), (c) treated with 10 ng/ml of IFN-λ1 or (d) treated with IFN-λ1 prior DENV-2 infection. Data points represent the mean of three replicates and error bars indicate standard deviation
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Fig9: Increase in SOCS1 coincides with a fall in IFN-λ1 transcription. The same values used in the graphs of Fig. 8 were re-plotted and sorted according to experimental condition: (a) mock-infected cells, (b) infected with DENV-2 (MOI = 0.1), (c) treated with 10 ng/ml of IFN-λ1 or (d) treated with IFN-λ1 prior DENV-2 infection. Data points represent the mean of three replicates and error bars indicate standard deviation

Mentions: In order to analyze other aspects of expression kinetics, the same data from Fig. 8 were re-plotted in Fig. 9 but grouped by experimental condition. Control cells (mock-infected) did not show significant activation of any gene tested, indicating that an external stimulus is required to activate their transcription in the evaluated conditions (Fig. 9a).Fig. 9


Interferon lambda inhibits dengue virus replication in epithelial cells.

Palma-Ocampo HK, Flores-Alonso JC, Vallejo-Ruiz V, Reyes-Leyva J, Flores-Mendoza L, Herrera-Camacho I, Rosas-Murrieta NH, Santos-López G - Virol. J. (2015)

Increase in SOCS1 coincides with a fall in IFN-λ1 transcription. The same values used in the graphs of Fig. 8 were re-plotted and sorted according to experimental condition: (a) mock-infected cells, (b) infected with DENV-2 (MOI = 0.1), (c) treated with 10 ng/ml of IFN-λ1 or (d) treated with IFN-λ1 prior DENV-2 infection. Data points represent the mean of three replicates and error bars indicate standard deviation
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4584467&req=5

Fig9: Increase in SOCS1 coincides with a fall in IFN-λ1 transcription. The same values used in the graphs of Fig. 8 were re-plotted and sorted according to experimental condition: (a) mock-infected cells, (b) infected with DENV-2 (MOI = 0.1), (c) treated with 10 ng/ml of IFN-λ1 or (d) treated with IFN-λ1 prior DENV-2 infection. Data points represent the mean of three replicates and error bars indicate standard deviation
Mentions: In order to analyze other aspects of expression kinetics, the same data from Fig. 8 were re-plotted in Fig. 9 but grouped by experimental condition. Control cells (mock-infected) did not show significant activation of any gene tested, indicating that an external stimulus is required to activate their transcription in the evaluated conditions (Fig. 9a).Fig. 9

Bottom Line: We found increased (~1.8 times) serological IFN-λ in dengue fever patients compared to healthy blood donors.The reduction of viral titer corresponded with increased ISG mRNA levels (MX1 and OAS1), with the highest inhibition occurring at ISG's peak expression.Mechanisms for the cellular and organismal interplay between DENV and IFN- λ need to be further studied as they could provide insights into strategies to treat this disease.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio de Biología Molecular y Virología, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Metepec, Puebla, México. hk.palma@gmail.com.

ABSTRACT

Background: In viral disease, infection is controlled at the cellular level by type I interferon (IFN-I), but dengue virus (DENV) has the ability to inhibit this response. Type III interferon, also known as lambda IFN (IFN-III or IFN-λ), is a complementary pathway to the antiviral response by IFN-I. This work analyzed the IFN-λ (IFN-III) mediated antiviral response against DENV serotype 2 (DENV-2) infection.

Methods: Dengue fever patients were sampled to determine their IFN-λ levels by ELISA. To study the IFN-λ response during DENV infection we selected the epithelial cell line C33-A, and we demonstrated that it is permissive to DENV-2 infection. The effect of IFN-λ on virus replication was determined in these cells, in parallel to the expression of IFN-stimulated genes (ISGs), and Suppressor of Cytokine Signaling (SOCS), genes measured by RT-qPCR.

Results: We found increased (~1.8 times) serological IFN-λ in dengue fever patients compared to healthy blood donors. IFN-λ inhibited DENV-2 replication in a dose-dependent manner in vitro. The reduction of viral titer corresponded with increased ISG mRNA levels (MX1 and OAS1), with the highest inhibition occurring at ISG's peak expression. Presence of IFN-negative regulators, SOCS1 and SOCS3, during DENV-2 infection was associated with reduced IFN-λ1 expression.

Conclusions: Evidence described here suggests that IFN-λ is a good candidate inhibitor of viral replication in dengue infection. Mechanisms for the cellular and organismal interplay between DENV and IFN- λ need to be further studied as they could provide insights into strategies to treat this disease. Furthermore, we report a novel epithelial model to study dengue infection in vitro.

No MeSH data available.


Related in: MedlinePlus