Chikungunya Virus: An Emergent Arbovirus to the South American Continent and a Continuous Threat to the World.

Chikungunya virus (CHIKV) is an arthropod-borne virus (arbovirus) of epidemic concern, transmitted by Aedes ssp. mosquitoes, and is the etiologic agent of a febrile and incapacitating arthritogenic illness responsible for millions of human cases worldwide. After major outbreaks starting in 2004, CHIKV spread to subtropical areas and western hemisphere coming from sub-Saharan Africa, South East Asia, and the Indian subcontinent. Even though CHIKV disease is self-limiting and non-lethal, more than 30% of the infected individuals will develop chronic disease with persistent severe joint pain, tenosynovitis, and incapacitating polyarthralgia that can last for months to years, negatively impacting an individual's quality of life and socioeconomic productivity. The lack of specific drugs or licensed vaccines to treat or prevent CHIKV disease associated with the global presence of the mosquito vector in tropical and temperate areas, representing a possibility for CHIKV to continually spread to different territories, make this virus an agent of public health burden. In South America, where Dengue virus is endemic and Zika virus was recently introduced, the impact of the expansion of CHIKV infections, and co-infection with other arboviruses, still needs to be estimated. In Brazil, the recent spread of the East/Central/South Africa (ECSA) and Asian genotypes of CHIKV was accompanied by a high morbidity rate and acute cases of abnormal disease presentation and severe neuropathies, which is an atypical outcome for this infection. In this review, we will discuss what is currently known about CHIKV epidemics, clinical manifestations of the human disease, the basic concepts and recent findings in the mechanisms underlying virus-host interaction, and CHIKV-induced chronic disease for both in vitro and in vivo models of infection. We aim to stimulate scientific debate on how the characterization of replication, host-cell interactions, and the pathogenic potential of the new epidemic viral strains can contribute as potential developments in the virology field and shed light on strategies for disease control.

Tucum-do-cerrado (Bactris setosa Mart.) modulates oxidative stress, inflammation, and apoptosis-related proteins in rats treated with azoxymethane.

Oxidative and inflammatory responses play an important role in the development and prevention of cancer, with both responses being modulated by phytochemical compounds. This study investigated the chemopreventive effect of tucum-do-cerrado fruit in rats treated with azoxymethane. Wistar rats were treated for 12 weeks with: a control diet (CT); a control diet + AOM (CT/DR); a control diet + 15% tucum-do-cerrado (TU); or a control diet + 15% tucum-do-cerrado + AOM (TU/DR). The association of tucum-do-cerrado and AOM (TU/DR) increased glutathione-S-transferase activity, decreased MDA levels, increased levels of COX2, TNFα and BAX, and decreased Bcl2/Bax ratio, compared to the CT/DR group. Carbonyl levels, IL-1ß and IL-6 mRNA levels, and aberrant crypt foci showed no difference between the treatments. In conclusion, tucum-do-cerrado reduced lipid oxidative damage, induced a pro-inflammatory effect, and promoted a pro-apoptotic "environment" in rats treated with AOM; however no changes in aberrant crypts were observed.

Autochthonous Transmission of East/Central/South African Genotype Chikungunya Virus, Brazil.

We isolated East/Central/South African genotype chikungunya virus during the 2016 epidemic in Rio de Janeiro, Brazil. Genome sequencing revealed unique mutations in the nonstructural protein 4 (NSP4-A481D) and envelope protein 1 (E1-K211T). Moreover, all Brazil East/Central/South isolates shared the exclusive mutations E1-M407L and E2-A103T.

Tucum-Do-Cerrado (Bactris setosa Mart.) Consumption Modulates Iron Homeostasis and Prevents Iron-Induced Oxidative Stress in the Rat Liver.

This study investigated the effect of tucum-do-cerrado consumption in the oxidative status of iron-supplemented rats. Four groups of rats were treated: Control (AIN-93G), Tuc (AIN-93G added of tucum-do-cerrado), Fe (AIN-93G iron-enriched), or TucFe (AIN-93G with tucum-do-cerrado and iron-enriched) diet, for 30 days. Iron-enriched diet increased serum, liver, spleen, and intestine iron levels; transferrin saturation; liver lipid oxidation; mRNA levels of hepatic Hamp and Bmp6, and Nrf2 in the intestine. Tucum-do-cerrado consumption reduced spleen lipid and protein oxidation; mRNA levels of hepatic Hamp and Ftl, and increased serum antioxidant capacity and hepatic mRNA levels of Bmp6, Hmox1, Nqo1, and Nrf2. TucFe diet consumption abrogated the liver Hamp iron-induced up-regulation, prevented intestinal iron accumulation; hepatic lipid peroxidation; splenic protein damage, and the increase of catalase, glutathione reductase, and glutathione peroxidase activity in some tissues. These results suggest that tucum-do-cerrado protects tissues against oxidative damage, by reducing iron availability in liver and consequently inhibiting liver Hamp expression.

Vitamin A deficiency modulates iron metabolism via ineffective erythropoiesis.

Vitamin A modulates inflammatory status, iron metabolism and erythropoiesis. Given that these factors modulate the expression of the hormone hepcidin (Hamp), we investigated the effect of vitamin A deficiency on molecular biomarkers of iron metabolism, the inflammatory response and the erythropoietic system. Five groups of male Wistar rats were treated: control (AIN-93G), the vitamin A-deficient (VAD) diet, the iron-deficient (FeD) diet, the vitamin A- and iron-deficient (VAFeD) diet or the diet with 12 mg atRA/kg diet replacing all-trans-retinyl palmitate by all-trans retinoic acid (atRA). Vitamin A deficiency reduced serum iron and transferrin saturation levels, increased spleen iron concentrations, reduced hepatic Hamp and kidney erythropoietin messenger RNA (mRNA) levels and up-regulated hepatic and spleen heme oxygenase-1 gene expression while reducing the liver HO-1 specific activity compared with the control. The FeD and VAFeD rats exhibited lower levels of serum iron and transferrin saturation, lower iron concentrations in tissues and lower hepatic Hamp mRNA levels compared with the control. The treatment with atRA resulted in lower serum iron and transferrin concentrations, an increased iron concentration in the liver, a decreased iron concentration in the spleen and in the gut, and decreased hepatic Hamp mRNA levels. In summary, these findings suggest that vitamin A deficiency leads to ineffective erythropoiesis by the down-regulation of renal erythropoietin expression in the kidney, resulting in erythrocyte malformation and the consequent accumulation of the heme group in the spleen. Vitamin A deficiency indirectly modulates systemic iron homeostasis by enhancing erythrophagocytosis of undifferentiated erythrocytes.

Co-occurrence of sporadic parkinsonism and late-onset Alzheimer's disease in a Brazilian male with the LRRK2 p.G2019S mutation.

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene represent the most common known genetic cause of inherited and idiopathic Parkinson's disease (PD) in different populations. The predicted multifunctionality of LRRK2 product and the pleomorphic pathology associated with LRRK2 mutations place this gene as a potential candidate for other neurodegenerative disorders, mainly Alzheimer's disease (AD). We report a Brazilian male expressing both late-onset AD and slowly progressive parkinsonism signs, and who presented the most frequent LRRK2 mutation (p.G2019S). Although the co-occurrence of PD and AD would be expected occasionally, the shared mechanisms between the two complex disorders are still unclear and are discussed herein. In light of recent findings about the wide role of LRRK2 under normal and pathological conditions, it is tempting to speculate that LRRK2 mutations might play an upstream influence on the etiology of not just PD but also several alpha-synuclein and tau pathologies, including AD.