Ana Luiza Pamplona Mosimann

In the early 2015, several cases of patients presenting symptoms of mild fever, rash, conjunctivitis and arthralgia were reported in the northeastern Brazil. Although all patients lived in a dengue endemic area, molecular and serological diagnosis for dengue resulted negative. Chikungunya virus infection was also discarded. Subsequently, Zika virus (ZIKV) was detected by reverse transcription-polymerase chain reaction from the sera of eight patients and the result was confirmed by DNA sequencing. Phylogenetic analysis suggests that the ZIKV identified belongs to the Asian clade. This is the first report of ZIKV infection in Brazil.

Ilex paraguariensis aqueous extract (mate) is an antioxidant-rich beverage widely consumed in South American countries. Here we questioned whether mate could reduce the progression of atherosclerosis in 1% cholesterol-fed rabbits. New Zealand White male rabbits (n = 32) were divided into four groups: control (C, n = 5), control-mate (CM, n = 5), hypercholesterolemic (HC, n = 11) and hypercholesterolemic-mate (HCM, n = 11). The daily water and mate extract consumption was approximately 400 ml. After 2 months of treatment, mate intake did not change the lipid profile or hepatic cholesterol content of control or hypercholesterolemic rabbits (p < 0.05). However, the atherosclerotic lesion area was considerably smaller in the hypercholesterolemic-mate group (HCM, 35.4% vs. HC, 60.1%; p < 0.05). In addition, the aortic cholesterol content was around half that of the HC group (HCM, 36.8 vs. HC, 73.9 microg/mg of protein, p < 0.05). In spite of this, the thiobarbituric acid-reactive substances (TBARS) in the atherosclerotic aorta, liver and serum, and the activity of the antioxidant enzymes in liver and aorta did not differ among groups (p > 0.05). The results showed that Ilex paraguariensis extract can inhibit the progression of atherosclerosis in cholesterol-fed rabbits, although it did not decrease the serum cholesterol or aortic TBARS and antioxidant enzymes.

Social and epidemiological aspects of dengue were evaluated in an important metropolitan area in southern Brazil, from August 2012 to September 2014. Demographic, clinical, serological data were collected from patients with acute dengue symptoms treated at public health system units (HSUs). A systematic approach to analyze the spatial and temporal distribution of cases was developed, considering the temporal cross-correlation between dengue and weather, and the spatial correlation between dengue and income over the city's census tracts. From the 878 patients with suggestive symptoms, 249 were diagnosed as positive dengue infection (28%). Considering the most statistically significant census tracts, a negative correlation was found between mean income and dengue (r = -0.65; p = 0.02; 95% CI: -0.03 to -0.91). The occurrence of dengue followed a seasonal distribution, and it was found to be three and four months delayed in relation to precipitation and temperature, respectively. Unexpectedly, the occurrence of symptomatic patients without dengue infection followed the same seasonal distribution, however its spatial distribution did not correlate with income. Through this methodology, we have found evidence that suggests a relation between dengue and poverty, which enriches the debate in the literature and sheds light on an extremely relevant socioeconomic and public health issue.

The family Flaviviridae comprises a wide variety of viruses that are distributed worldwide, some of which are associated with high rates of morbidity and mortality. There are neither vaccines nor antivirals for most flavivirus infections, reinforcing the importance of research on different aspects of the viral life cycle. During infection, cytoplasmic accumulation of RNA fragments mainly originating from the 3' UTRs, which have been designated subgenomic flavivirus RNAs (sfRNAs), has been detected. It has been shown that eukaryotic exoribonucleases are involved in viral sfRNA production. Additionally, viral and human small RNAs (sRNAs) have also been found in flavivirus-infected cells, especially microRNAs (miRNAs). miRNAs were first described in eukaryotic cells and in a mature and functional state present as single-stranded 18-24 nt RNA fragments. Their main function is the repression of translation through base pairing with cellular mRNAs, besides other functions, such as mRNA degradation. Canonical miRNA biogenesis involves Drosha and Dicer, however miRNA can also be generated by alternative pathways. In the case of flaviviruses, alternative pathways have been suggested. Both sfRNAs and miRNAs are involved in viral infection and host cell response modulation, representing interesting targets of antiviral strategies. In this review, we focus on the generation and function of viral sfRNAs, sRNAs and miRNAs in West Nile, dengue, Japanese encephalitis, Murray Valley encephalitis and yellow fever infections, as well as their roles in viral replication, translation and cell immune response evasion. We also give an overview regarding other flaviviruses and the generation of cellular miRNAs during infection.

A recent (2007 to 2009) dengue outbreak caused by dengue virus (DENV) in Paraguay presented unusual severe clinical outcomes associated with 50% mortality rates. Although it has been reported that inflammatory responses influence the severity of dengue virus infection (T. Pang, M. J. Cardosa, and M. G. Guzman, Immunol. Cell Biol. 85:43-45, 2007), there remains a paucity of information on virus-innate immunity interactions influencing clinical outcome. Using human dendritic cells from a major innate immune cell population as an in vitro model, we have investigated signature cytokine responses as well as infectivity-replicative profiles of DENV clinical isolates from either a nonfatal case of classical dengue fever (strain DENV3/290; isolated in Brazil in 2002) or a fatal case of dengue fever with visceral complications isolated in Paraguay in 2007 (strain DENV3/5532). Strain DENV3/5532 was found to display significantly higher replicative ability than DENV3/290 in monocyte-derived dendritic cells (mdDCs). In addition, compared to DENV3/290 results, mdDCs exposed to DENV3/5532 showed increased production of proinflammatory cytokines associated with higher rates of programmed cell death, as shown by annexin V staining. The observed phenotype was due to viral replication, and tumor necrosis factor alpha (TNF-α) appears to exert a protective effect on virus-induced mdDC apoptosis. These results suggest that the DENV3/5532 strain isolated from the fatal case replicates within human dendritic cells, modulating cell survival and synthesis of inflammatory mediators.