Epithelial-to-mesenchymal transition induced by virus / Transición epitelio-mesénquima inducida por virus

RESUMEN La Transición Epitelio-Mesénquima (EMT) es un proceso de diferenciación altamente conservado en vertebrados. Este ocurre en células epiteliales con la activación progresiva de la pérdida de la polaridad, la adquisición de motilidad individual y la capacidad invasiva a otros tejidos. La EMT es un proceso normal durante el desarrollo; no obstante, en condiciones patológicas está relacionada con la inducción de metástasis, lo cual representa una vía alterna al desarrollo de procesos oncogénicos tempranos. Aunque la EMT es activada principalmente por factores de crecimiento, también se puede desencadenar por infecciones de patógenos intracelulares mediante la activación de rutas moleculares inductoras de este proceso. Por lo tanto, una infección bacteriana o viral pueda generar predisposición al desarrollo de tumores. Nuestro interés está enfocado principalmente en caracterizar la relación virus-hospedero, y en el caso de los virus, varios ya se han descrito como inductores de la EMT. En este artículo de revisión se describen el fenómeno de la plasticidad celular y la ocurrencia detallada del proceso de EMT, los patógenos virales reportados como inductores, los mecanismos moleculares usados para ello y las vías de regulación mediante miRNAs. Por último, se discute cómo esta relación virus-hospedero puede explicar la patogénesis de la enfermedad causada por Dengue virus, favoreciendo la identificación de blancos moleculares para terapia, estrategia conocida como Antivirales dirigidos a blancos celulares o HTA (Host-targeting antivirals).

ABSTRACT Epithelial-to-Mesenchymal Transition (EMT) is a highly conserved dedifferentiation process in vertebrates. This process occurs in epithelial cells activating progressive loss of cell polarity, acquisition of individual motility and invasive capacity to other tissues. EMT is a normal process during development process, however, in pathological conditions is related to the induction of metastasis, which represents an alternative path to the development of early oncogenic processes. Although, EMT is mainly activated by growth factors, it can also be triggered by intracellular-pathogen-infections by activating molecular pathways that induce this process. Therefore, a bacterial or viral infection may generate predisposition to the development of tumors. Our interest is mainly focused on characterizing the host-virus relationship, and in the case of viruses, several have already been described as EMT inductors. In this review, phenomenon of cellular plasticity, detailed occurrence of the EMT, viral pathogens reported as inducers, the molecular mechanisms, and the regulatory pathways through miRNAs are described. Finally, we discuss how this host-virus relationship may explain the pathogenesis of the disease caused by Dengue virus, favoring the identification of molecular targets for therapy, a strategy known as Host-Targeting Antivirals (HTA).

Coronavirus persistence in human respiratory tract and cell culture: An overview

ABSTRACT Emerging human coronaviruses, including the recently identified SARS-CoV-2, are relevant respiratory pathogens due to their potential to cause epidemics with high case fatality rates, although endemic coronaviruses are also important for immunocompromised patients. Long-term coronavirus infections had been described mainly in experimental models, but it is currently evident that SARS-CoV-2 genomic-RNA can persist for many weeks in the respiratory tract of some individuals clinically recovered from coronavirus infectious disease-19 (COVID-19), despite a lack of isolation of infectious virus. It is still not clear whether persistence of such viral RNA may be pathogenic for the host and related to long-term sequelae. In this review, we summarize evidence of SARS-CoV-2 RNA persistence in respiratory samples besides results obtained from cell culture and histopathology describing long-term coronavirus infection. We also comment on potential mechanisms of coronavirus persistence and relevance for pathogenesis.

Resolution of immune response by recombinant transforming growth factor-beta (rTGF-β) during influenza A virus infection.

Background & objectives: Replication of influenza A virus in the respiratory tract leads to cell damage and liberation of cytokines and chemokines. The in vivo cytokine induction and modulation by recombinant transforming growth factor- β1 (rTGF-β1) has not been studied. Therefore, in the present study the effect of rTGF-β1, a potent immunomodulatory cytokine which has anti-inflammatory properties and downregulates the release of inflammatory molecules, against influenza-virus infection in the airway of mice was investigated. Methods: rTGF-β1 was administered intravenously to mice with concomitant intranasal infection of influenza A/Udorn/317/72 (H3N2) virus, and the survival rate, virus titre, histopathological changes and levels of factors regulating inflammation in the airway fluid were analysed. Result: The immune response to influenza A virus was characterized by an influx of both macrophages and lymphocytes into the lungs of the infected host. rTGF-β1 significantly suppressed virus multiplication and improved the survival rate of mice. rTGF-β1 downregulated infiltration of neutrophils and the release of inflammatory molecules, such as interferon-gamma (IFN-γ), interleukin-1 β (IL-1β) and stimulated release of IL-10 that potentiates anti-inflammatory response into airway. Interpretation & conclusions: A generalized pulmonary inflammation does not contribute to viral clearance but represents an immunological background within which antiviral immunity operates. Treatment with rTGF-β1 reduced macrophage count and neutrophils influx in lungs of infected mice.

Papel de las prtteínas reguladoras y accesorias del vih-1 en la patogénesis de esa infección / Role of the regulatory and accesory proteins of HIV- 1 in its pathogenisis

Desde el descubrimiento del virus de inmunodeficiencia humana tipo 1 (VIH-1) como agente etiológico del síndrome de inmunodeficiencia adquirida (SIDA) se han descrito los procesos más importantes que hacen parte del ciclo replicativo del virus y que a su vez participan de la fisiopatología tan compleja que caracteriza a esta infección. A pesar de los avances realizados en el desarrollo de medicamentos antirretrovirales y de los logros alcanzados en el control de la replicación viral, hechos que se reflejan en un aumento en la expectativa y calidad de vida de los individuos infectados, la terapia actual no permite una reconstitución inmunológica total y está acompañada de efectos tóxicos secundarios y de la aparición de resistencia viral. Esto ha obligado a mantener la búsqueda constante de nuevos blancos terapéuticos que ofrezcan alternativas en la lucha contra esta pandemia. Hasta hace pocos años se creía que las proteínas accesorias y reguladoras del VIH1 no ejercían un papel significativo en el ciclo replicativo del virus y en la patogénesis de la infección; sin embargo, estudios recientes indican que estas proteínas ejercen funciones esenciales en diferentes etapas del proceso replicativo y por ende son responsables de muchos efectos asociados a la patogénesis viral. Por estos hallazgos, las proteínas accesorias y reguladoras del VIH-1 constituyen un blanco promisorio en el desarrollo de nuevos medicamentos que complementen los antirretrovirales disponibles en la actualidad. En esta revisión se describe la función de las proteínas reguladoras y accesorias del VIH-1 en el ciclo replicativo viral y su participación en el proceso patogénico de esta infección.

Since the discovery of HIV-1 as the etiological agent of the acquired immunodeficiency syndrome (AIDS), the main processes involved in its replication cycle and responsible for the complex physiopathology of this infection have been described. Despite the advances in the development of new antiretrovirals and their impact in the quality and life expectancy of infected individuals, the current therapy does not allow a complete immune reconstitution and is also associated with deleterious side effects and the appearance of viral resistance. Therefore the search for new therapeutic targets is required to face this pandemic. The role of the accessory and regulatory proteins of the HIV- 1 in the replication cycle and in the pathogenesis of the infection has been ignored for several years now; however, recent studies indicated that these proteins play essential roles in the replication cycle, being responsible for several processes associated to viral pathogenesis. These findings have underlined the importance of these proteins as promissory targets in the development of new therapeutic agents. In this review, we detailed the role of each one of the HIV-1’s regulatory and accessory proteins in the replicative cycle and in the pathogenesis of this infection.