Limits...
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.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.

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
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
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


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.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.

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