FLAVIVIRUSES 1103 Background and Classification 1103 Structure and Physical Properties of the Virion 1104 Binding and Entry 1105 Genome Structure 1106 Translation and Proteolytic Processing 1107 Features of the Structural Proteins 1108 Features of the Nonstructural Proteins 1109 RNA Replication 1112 Membrane Reorganization and the Compartmentalization of Flavivirus Replication 1112 Assembly and Release of Particles from Flavivirus-infected Cells 1112 Host Resistance to Flavivirus Infection 1113

Flaviviridae :T he Viruses and Their Replication

The interferon (IFN) system is an extremely powerful antiviral response that is capable of controlling most, if not all, virus infections in the absence of adaptive immunity. However, viruses can still replicate and cause disease in vivo, because they have some strategy for at least partially circumventing the IFN response. We reviewed this topic in 2000 [Goodbourn, S., Didcock, L. & Randall, R. E. (2000). J Gen Virol 81, 2341-2364] but, since then, a great deal has been discovered about the molecular mechanisms of the IFN response and how different viruses circumvent it. This information is of fundamental interest, but may also have practical application in the design and manufacture of attenuated virus vaccines and the development of novel antiviral drugs. In the first part of this review, we describe how viruses activate the IFN system, how IFNs induce transcription of their target genes and the mechanism of action of IFN-induced proteins with antiviral action. In the second part, we describe how viruses circumvent the IFN response. Here, we reflect upon possible consequences for both the virus and host of the different strategies that viruses have evolved and discuss whether certain viruses have exploited the IFN response to modulate their life cycle (e.g. to establish and maintain persistent/latent infections), whether perturbation of the IFN response by persistent infections can lead to chronic disease, and the importance of the IFN system as a species barrier to virus infections. Lastly, we briefly describe applied aspects that arise from an increase in our knowledge in this area, including vaccine design and manufacture, the development of novel antiviral drugs and the use of IFN-sensitive oncolytic viruses in the treatment of cancer.

Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures.

Composition and three-dimensional architecture of the dengue virus replication and assembly sites.

The interferon response circuit: Induction and suppression by pathogenic viruses

https://www.cell.com/cell-host-microbe/pdf/S1931-3128(16)30205-0.pdf

Zika Virus Targets Human STAT2 to Inhibit Type I Interferon Signaling

Dengue virus is a worldwide-distributed mosquito-borne flavivirus with a positive strand RNA genome. Its transcribed polyprotein is cleaved by host- and virus-encoded peptidases into 10 proteins, some of which are of unknown function. Although dengue virus-infected cells seem to be resistant to the antiviral action of IFN, the viral products that mediate this resistance are unknown. Therefore, we have analyzed the ability of the 10 dengue virus-encoded proteins to antagonize the IFN response. We found that expression in human A549 cells of the dengue virus nonstructural proteins NS2A, NS4A, or NS4B enhances replication of an IFN-sensitive virus. Moreover, expression of NS4B and, to a lesser extent, of NS2A and NS4A proteins results in down-regulation of IFN-β-stimulated gene expression. Cells expressing NS4B or infected with dengue virus do not exhibit nuclear signal transducer and activator of transcription (STAT) 1 on treatment with IFN-β or IFN-γ, indicating that NS4B might be involved in blocking IFN signaling during dengue virus infections. This protein, encoded by a positive strand RNA virus, is implicated as an IFN-signaling inhibitor.

https://www.pnas.org/content/pnas/100/24/14333.full.pdf

Inhibition of interferon signaling by dengue virus

INTRODUCTION
Previous studies that identified the prognostic factors for the severity of the new coronavirus disease 2019 (COVID-19) in different populations have generated controversial conclusions. The lack of a standard definition of COVID-19 severity and the differences between clinical diagnoses might make it difficult to provide optimum care according to the characteristics of each population.


METHODOLOGY
We investigated the factors that impacted the severe outcome or death from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients treated at the Mexican Institute of Social Security in Yucatán, México in 2020. A cross-sectional study of COVID-19 confirmed cases was done to know the prevalence and association of the demographic and clinical characteristics with a severe or fatal outcome. Information from the National Epidemiological Surveillance System (SINAVE) database was used and SPSS v 21 was used for statistical analyses. We used the World Health Organization (WHO) and the Centers for Diseases Control and Prevention (CDC) symptomatology classifications to define severe cases.


RESULTS
Diabetes and pneumonia increased the risk of death and having diabetes was a prognostic factor for severe illness following SARS-CoV-2 infection.


CONCLUSIONS
Our results highlight the influence of cultural and ethnic factors, the necessity to standardize the parameters for clinical diagnoses, and to use the same criteria for the definition of COVID-19 severity to establish the clinical conditions that contribute to the pathophysiology of this disease in each population.

https://www.jidc.org/index.php/journal/article/download/37159885/3049

Prognostic factors of COVID-19 severity and mortality in the Yucatecan ethnic of México contrast with other populations.

It is acknowledged that antiviral immune response contributes to dengue immunopathogenesis. To identify immunological markers that distinguish dengue fever (DF) and dengue hemorrhagic fever (DHF), 113 patients with confirmed dengue infection were analyzed at 6 or 7 days after fever onset. Peripheral blood mononuclear cells (PBMC) were isolated, lymphocyte subsets and activation biomarkers were identified by flow cytometry, and differentiation of T helper (Th) lymphocytes was achieved by the relative expression analysis of T-bet (Th1), GATA-3 (Th2), ROR-γ (Th17), and FOXP-3 (T regulatory) transcription factors quantified by real-time PCR. CD8+, CD40L+, and CD45+ cells show higher numbers in DF compared to DHF patients, whereas CD4+, CD19+, and CD25+ cells show higher numbers in DHF than DF patients. High expression of GATA-3 accompanied by low expression of T-bet indicates predominance of Th2 response. In addition, higher expression of FOXP-3 and reduced functional cytotoxic T cells (CD8+perforin+) were observed in DHF patients. In further experiments, PBMC were stimulated ex vivo with dengue virus E, NS3, NS4, and NS5 peptides, and proliferating T cell subsets were determined. Lower proliferative responses to NS3 and NS4 peptides and reduced CD8+ cytotoxic T cells were observed in DHF patients. Our results suggest that immune response to dengue is dysregulated with predominance of CD4+ T cells, low activation of Th1 cells, and downregulation of the antiviral cytotoxic activity during severe dengue, likely induced by regulatory T cells.

/pdf/low-activation-of-cd8-t-cells-in-response-to-viral-peptides-2ku40x1c.pdf

Gilma G. Sánchez-Burgos

Papers

Inhibition of interferon signaling by dengue virus

Prognostic factors of COVID-19 severity and mortality in the Yucatecan ethnic of México contrast with other populations.

Low Activation of CD8+ T Cells in response to Viral Peptides in Mexican Patients with Severe Dengue