ABSTRACT
In February 2016, the World Health Organization declared Zika virus (ZIKV) infection a public health emergency of international concern because it caused congenital Zika syndrome (CZS). The CZS is considered a specific pattern of birth defects caused by ZIKV infection, which is transmitted by the bite of the Aedes aegypti mosquito. The CZS clinical manifestations are broad and nonspecific, including microcephaly, subcortical calcifications, ocular alterations, congenital contractures, early hypertonia, and pyramidal as well as extrapyramidal symptoms. The ZIKV has gained great importance because it has affected a large percentage of the population worldwide during the last few years, despite the measures implemented by international organizations. The pathophysiology and non-vectorial transmission routes of the virus are still under study. The diagnosis is made upon suspicion of ZIKV infection, the patient's clinical manifestations, and it is confirmed by molecular laboratory tests demonstrating the presence of viral particles. Unfortunately, there is no specific treatment or vaccine for this condition; however, patients receive multidisciplinary care and constant monitoring. Therefore, the strategies that have been implemented are directed toward preventive measures and vector control.
En febrero de 2016, la Organización Mundial de la Salud declaró a la infección por virus Zika una emergencia de salud pública de importancia internacional por ser la causa del síndrome congénito por virus Zika. Este síndrome es considerado un patrón específico de defectos al nacimiento causados por la infección por virus Zika, que se transmite por la picadura del mosquito vector Aedes aegypti y cuyas manifestaciones clínicas son amplias e inespecíficas, entre las que destacan microcefalia, calcificaciones subcorticales, alteraciones oculares, contracturas congénitas, hipertonía temprana y síntomas de afectación piramidal y extrapiramidal. Este virus ha tomado gran importancia debido a que durante los últimos años ha afectado a un gran porcentaje de la población en todo el mundo, a pesar de las medidas implementadas por organizaciones internacionales. La fisiopatología y las vías de transmisión no vectorial de la infección aún siguen en estudio. El diagnóstico se realiza ante la sospecha por las manifestaciones clínicas del paciente, y se confirma mediante pruebas moleculares de laboratorio en las que se demuestre la presencia de partículas virales. Desafortunadamente, no existe aún un tratamiento ni una vacuna específica para este padecimiento; sin embargo, los pacientes reciben cuidados multidisciplinarios y monitorización constante. Las estrategias que se han implementado se dirigen hacia medidas preventivas de la infección y el control de los vectores.
Subject(s)
Microcephaly , Zika Virus Infection , Zika Virus , Animals , HumansABSTRACT
Abstract In February 2016, the World Health Organization declared Zika virus (ZIKV) infection a public health emergency of international concern because it caused congenital Zika syndrome (CZS). The CZS is considered a specific pattern of birth defects caused by ZIKV infection, which is transmitted by the bite of the Aedes aegypti mosquito. The CZS clinical manifestations are broad and nonspecific, including microcephaly, subcortical calcifications, ocular alterations, congenital contractures, early hypertonia, and pyramidal as well as extrapyramidal symptoms. The ZIKV has gained great importance because it has affected a large percentage of the population worldwide during the last few years, despite the measures implemented by international organizations. The pathophysiology and non-vectorial transmission routes of the virus are still under study. The diagnosis is made upon suspicion of ZIKV infection, the patient's clinical manifestations, and it is confirmed by molecular laboratory tests demonstrating the presence of viral particles. Unfortunately, there is no specific treatment or vaccine for this condition; however, patients receive multidisciplinary care and constant monitoring. Therefore, the strategies that have been implemented are directed toward preventive measures and vector control.
Resumen En febrero de 2016, la Organización Mundial de la Salud declaró a la infección por virus Zika una emergencia de salud pública de importancia internacional por ser la causa del síndrome congénito por virus Zika. Este síndrome es considerado un patrón específico de defectos al nacimiento causados por la infección por virus Zika, que se transmite por la picadura del mosquito vector Aedes aegypti y cuyas manifestaciones clínicas son amplias e inespecíficas, entre las que destacan microcefalia, calcificaciones subcorticales, alteraciones oculares, contracturas congénitas, hipertonía temprana y síntomas de afectación piramidal y extrapiramidal. Este virus ha tomado gran importancia debido a que durante los últimos años ha afectado a un gran porcentaje de la población en todo el mundo, a pesar de las medidas implementadas por organizaciones internacionales. La fisiopatología y las vías de transmisión no vectorial de la infección aún siguen en estudio. El diagnóstico se realiza ante la sospecha por las manifestaciones clínicas del paciente, y se confirma mediante pruebas moleculares de laboratorio en las que se demuestre la presencia de partículas virales. Desafortunadamente, no existe aún un tratamiento ni una vacuna específica para este padecimiento; sin embargo, los pacientes reciben cuidados multidisciplinarios y monitorización constante. Las estrategias que se han implementado se dirigen hacia medidas preventivas de la infección y el control de los vectores.
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.
