Background: There is a lack of specific antiviral therapy against dengue virus (DENV) in current use. Therefore, a great proportion of dengue cases progress to severe clinical forms due to a complex interplay between virus and host immune response. It has been hypothesized that heterotypic non-neutralizing antibodies enhance DENV infection in phagocytic cells, and this induces an inflammatory response that is involved in the pathogenesis of severe dengue. Purpose: To identify the antiviral and immunomodulatory effects of polyphenols on dengue virus infection. Methods: Human U937-DC-SIGN macrophages were infected with DENV serotypes 2 or 3 in the presence or not of enhancing antibody 4G2. Viral titers and the secretion of tumor necrosis factor-alpha, IL-6, IL-10 and interferon-alpha were analyzed timely. Results: DENV infection alone induced high production of IL-6 and TNF-α, but in the presence of 4G2 antibody, viral titers and TNF-α secretion were potentiated. Based on anti-inflammatory antecedents, the polyphenols curcumin, fisetin, resveratrol, apigenin, quercetin and rutin were tested for antiviral and immunomodulatory properties. Only quercetin and fisetin inhibited DENV-2 and DENV-3 infection in the absence or presence of enhancing antibody (>90%, p<0.001); they also inhibited TNF-α and IL-6 secretion (p<0.001). Conclusion: Quercetin and fisetin down-regulate the production of proinflammatory cytokines induced by DENV infection enhanced by antibodies a mechanism involved in severe dengue.

An analysis of the conjugative transfer of pRetCFN42d, the symbiotic plasmid (pSym) of Rhizobium etli , has revealed a novel gene, rctA , as an essential element of a regulatory system for silencing the conjugative transfer of R. etli pSym by repressing the transcription of conjugal transfer genes in standard laboratory media. The rctA gene product lacks sequence conservation with other proteins of known function but may belong to the winged-helix DNA-binding subfamily of transcriptional regulators. Similar to that of many transcriptional repressors, rctA transcription seems to be positively autoregulated. rctA expression is greatly reduced upon overexpression of another gene, rctB , previously identified as a putative activator of R. etli pSym conjugal transfer. Thus, rctB seems to counteract the repressive action of rctA. rctA homologs are present in at least three other bacterial genomes within the order Rhizobiales , where they are invariably located adjacent to and divergently transcribed from putative virB -like operons. We show that similar to that of R. etli pSym, conjugative transfer of the 1.35-Mb symbiotic megaplasmid A of Sinorhizobium meliloti is also subjected to the inhibitory action of rctA . Our data provide strong evidence that the R. etli and S. meliloti pSym plasmids are indeed self-conjugative plasmids and that this property would only be expressed under optimal, as yet unknown conditions that entail inactivation of the rctA function. The rctA gene seems to represent novel but probably widespread regulatory systems controlling the transfer of conjugative elements within the order Rhizobiales .

Zika virus (ZIKV) is a mosquito-borne pathogen, and Aedes aegypti has been identified as the main vector of the disease. Other mosquito species in the Aedes and Culex genera have been suggested to have the potential for being competent vectors based on experimental exposition of mosquitoes to an infectious blood meal containing ZIKV. Here, we report the isolation in cell culture of ZIKV obtained from different body parts of wild-caught female mosquitoes (Ae. aegypti, Ae. vexans, Cx. quinquefasciatus, Cx. coronator, and Cx. tarsalis) and whole male mosquitoes (Ae. aegypti and Cx. quinquefasciatus) in Mexico. Importantly, this is the first report that shows the presence of the virus in the salivary glands of the wild-caught female mosquitoes species, Cx. coronator, Cx. tarsalis, and Ae. vexans. Our findings strongly suggest that all the species reported herein are potential vectors for ZIKV.

Dengue is an important and growing public health problem worldwide with an estimated 100million new clinical cases annually. Currently, no licensed drug or vaccine is available. During natural infection in humans, liver cells constitute one of the main targets of dengue virus (DENV) replication. However, a clear understanding of dengue pathogenesis remains elusive. In order to gain a better reading of the cross talk between virus and host cell proteins, we used a proteomics approach to analyze the host response to DENV infection in a hepatic cell line Huh-7. Differences in proteome expression were assayed 24h post-infection using label-free LC-MS. Quantitative analysis revealed 155 differentially expressed proteins, 64 of which were up-regulated and 91 down-regulated. These results reveal an important decrease in the expression of enzymes involved in the glycolytic pathway, citrate cycle, and pyruvate metabolism. This study provides large-scale quantitative information regarding protein expression in the early stages of infection that should be useful for better compression of the pathogenesis of dengue. Dengue infection involves alterations in the homeostasis of the host cell. Defining the interactions between virus and cell proteins should provide a better understanding of how viruses propagate and cause disease. Here, we present for the first time the proteomic analysis of hepatocytes (Huh-7 cells) infected with DENV-2 by label-free LC-MS.