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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

Kinetics of DENV-2 infection inhibition by IFN-λ. C33-A cells were untreated or treated with 10 ng/ml of (a) IFN-λ1 or (b) IFN-λ2 for 6 h prior to infection with DENV-2, which was performed at two different infectious doses (MOI = 0.1 and 1.0). The viral supernatant was titrated by plaque assays at 0, 6, 12, 18, 24 and 48 h post-infection. The points are representative of two independent experiments performed in triplicate
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Fig6: Kinetics of DENV-2 infection inhibition by IFN-λ. C33-A cells were untreated or treated with 10 ng/ml of (a) IFN-λ1 or (b) IFN-λ2 for 6 h prior to infection with DENV-2, which was performed at two different infectious doses (MOI = 0.1 and 1.0). The viral supernatant was titrated by plaque assays at 0, 6, 12, 18, 24 and 48 h post-infection. The points are representative of two independent experiments performed in triplicate

Mentions: Subsequently, viral replication in the C33-A cells was determined on lytic plaque-forming assays at different time post-infection (0, 6, 12, 18, 24 and 48 h). Two infectious doses (MOI = 0.1 and 1.0) were assayed. Cells pretreated with 10 ng/ml of IFN-λ1 (Fig. 6a) or IFN-λ2 (Fig. 6b) for 6 h prior to infection were compared to cells that were infected but not treated with IFN. The plots show an equivalent effect of IFN-λ1 and IFN-λ2 pre-treatment on viral titers, which were reduced by 1.5–2 logs with respect to mock-treated cells.Fig. 6


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)

Kinetics of DENV-2 infection inhibition by IFN-λ. C33-A cells were untreated or treated with 10 ng/ml of (a) IFN-λ1 or (b) IFN-λ2 for 6 h prior to infection with DENV-2, which was performed at two different infectious doses (MOI = 0.1 and 1.0). The viral supernatant was titrated by plaque assays at 0, 6, 12, 18, 24 and 48 h post-infection. The points are representative of two independent experiments performed in triplicate
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig6: Kinetics of DENV-2 infection inhibition by IFN-λ. C33-A cells were untreated or treated with 10 ng/ml of (a) IFN-λ1 or (b) IFN-λ2 for 6 h prior to infection with DENV-2, which was performed at two different infectious doses (MOI = 0.1 and 1.0). The viral supernatant was titrated by plaque assays at 0, 6, 12, 18, 24 and 48 h post-infection. The points are representative of two independent experiments performed in triplicate
Mentions: Subsequently, viral replication in the C33-A cells was determined on lytic plaque-forming assays at different time post-infection (0, 6, 12, 18, 24 and 48 h). Two infectious doses (MOI = 0.1 and 1.0) were assayed. Cells pretreated with 10 ng/ml of IFN-λ1 (Fig. 6a) or IFN-λ2 (Fig. 6b) for 6 h prior to infection were compared to cells that were infected but not treated with IFN. The plots show an equivalent effect of IFN-λ1 and IFN-λ2 pre-treatment on viral titers, which were reduced by 1.5–2 logs with respect to mock-treated cells.Fig. 6

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