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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

Dengue fever patients enhance their IFN-λ1 levels in blood. IFN-λ1/λ3 levels (pg/ml) in serums from clinical dengue patients and healthy donors were measured by ELISA. The experiment was done by triplicate and reproduced once. Error bars represent standard deviations, *** means p < 0.001
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Fig1: Dengue fever patients enhance their IFN-λ1 levels in blood. IFN-λ1/λ3 levels (pg/ml) in serums from clinical dengue patients and healthy donors were measured by ELISA. The experiment was done by triplicate and reproduced once. Error bars represent standard deviations, *** means p < 0.001

Mentions: To detect the presence of IFN-λ during DENV infection, serum samples from patients with dengue fever were analyzed by ELISA. Levels of IFN-λ (λ1/λ3) were determined in serum samples from 10 patients with dengue fever and 10 healthy blood donors. Figure 1 shows the value distribution for each group; the mean was 106.9 ± 9.05 pg/ml for DF patients and 58.71 ± 6.86 pg/ml (p < 0.001) for healthy donors.Fig. 1


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)

Dengue fever patients enhance their IFN-λ1 levels in blood. IFN-λ1/λ3 levels (pg/ml) in serums from clinical dengue patients and healthy donors were measured by ELISA. The experiment was done by triplicate and reproduced once. Error bars represent standard deviations, *** means p < 0.001
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: Dengue fever patients enhance their IFN-λ1 levels in blood. IFN-λ1/λ3 levels (pg/ml) in serums from clinical dengue patients and healthy donors were measured by ELISA. The experiment was done by triplicate and reproduced once. Error bars represent standard deviations, *** means p < 0.001
Mentions: To detect the presence of IFN-λ during DENV infection, serum samples from patients with dengue fever were analyzed by ELISA. Levels of IFN-λ (λ1/λ3) were determined in serum samples from 10 patients with dengue fever and 10 healthy blood donors. Figure 1 shows the value distribution for each group; the mean was 106.9 ± 9.05 pg/ml for DF patients and 58.71 ± 6.86 pg/ml (p < 0.001) for healthy donors.Fig. 1

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