Fatal Outcome of Chikungunya Virus Infection in Brazil.

BACKGROUND: Chikungunya virus (CHIKV) emerged in the Americas in 2013 and has caused approximately 2.1 million cases and >600 deaths. A retrospective investigation was undertaken to describe clinical, epidemiological, and viral genomic features associated with deaths caused by CHIKV in Ceará state, northeast Brazil. METHODS: Sera, cerebrospinal fluid (CSF), and tissue samples from 100 fatal cases with suspected arbovirus infection were tested for CHIKV, dengue virus (DENV), and Zika virus (ZIKV). Clinical, epidemiological, and death reports were obtained for patients with confirmed CHIKV infection. Logistic regression analysis was undertaken to identify independent factors associated with risk of death during CHIKV infection. Phylogenetic analysis was conducted using whole genomes from a subset of cases. RESULTS: Sixty-eight fatal cases had CHIKV infection confirmed by reverse-transcription quantitative polymerase chain reaction (52.9%), viral antigen (41.1%), and/or specific immunoglobulin M (63.2%). Co-detection of CHIKV with DENV was found in 22% of fatal cases, ZIKV in 2.9%, and DENV and ZIKV in 1.5%. A total of 39 CHIKV deaths presented with neurological signs and symptoms, and CHIKV-RNA was found in the CSF of 92.3% of these patients. Fatal outcomes were associated with irreversible multiple organ dysfunction syndrome. Patients with diabetes appear to die at a higher frequency during the subacute phase. Genetic analysis showed circulation of 2 CHIKV East-Central-South African (ECSA) lineages in Ceará and revealed no unique virus genomic mutation associated with fatal outcome. CONCLUSIONS: The investigation of the largest cross-sectional cohort of CHIKV deaths to date reveals that CHIKV-ECSA strains can cause death in individuals from both risk and nonrisk groups, including young adults.

Incidence of viral hepatitis in Brazil from 2009 to 2018: an epidemiological study of confirmed cases of viral hepatitis

Abstract INTRODUCTION: Viral hepatitis is a major public health problem. It is necessary to understand the epidemic, verifying the combination of biological and demographic characteristics. METHODS: This is an analytical ecological and epidemiological study. Confirmed case data from the Notification Disease Information System (SINAN) were used. RESULTS: From 2009-2018, SINAN confirmed 404,003 viral hepatitis cases in Brazil, with 12.49%, 37.06%, and 48.28% cases of hepatitis A, B, and C, respectively. CONCLUSIONS: In Brazil, 4,296 deaths were associated with viral hepatitis, of which 36.66% were associated with acute hepatitis B. The proportional distribution of cases varied among the five Brazilian regions.

Incidence of viral hepatitis in Brazil from 2009 to 2018: an epidemiological study of confirmed cases of viral hepatitis.

INTRODUCTION: Viral hepatitis is a major public health problem. It is necessary to understand the epidemic, verifying the combination of biological and demographic characteristics. METHODS: This is an analytical ecological and epidemiological study. Confirmed case data from the Notification Disease Information System (SINAN) were used. RESULTS: From 2009-2018, SINAN confirmed 404,003 viral hepatitis cases in Brazil, with 12.49%, 37.06%, and 48.28% cases of hepatitis A, B, and C, respectively. CONCLUSIONS: In Brazil, 4,296 deaths were associated with viral hepatitis, of which 36.66% were associated with acute hepatitis B. The proportional distribution of cases varied among the five Brazilian regions.

Using Accelerated Molecular Dynamics Simulation to elucidate the effects of the T198F mutation on the molecular flexibility of the West Nile virus envelope protein.

The envelope (E) protein is an important target for antibodies in flavivirus. Literature reports that the mutation T198F, located at the domain I-II hinge of the E protein, regulates viral breathing and increases the accessibility of a distal cryptic epitope located on the fusion loop, having a direct impact in the neutralization of West Nile virus (WNV). Our study aimed to describe, using accelerated molecular dynamics simulations, the effects of the T198F mutation in the flexibility of the E protein of WNV and to elucidate the mechanism that regulates epitope accessibility. The simulation results revealed that the mutation favors the formation of alternative hydrogen bonds, hampering the bending movement between domains I and II. We hypothesized that this is the mechanism by which the T198F mutation, located at the middle of the protein, locks the distal cryptc epitope near a single preferred conformation, rendering it more prone to recognition by antibodies.

Genomic screening of new putative antiviral lectins from Amazonian cyanobacteria based on a bioinformatics approach.

Lectins are proteins of nonimmune origin, which are capable of recognizing and binding to glycoconjugate moieties. Some of them can block the interaction of viral glycoproteins to the host cell receptors acting as antiviral agents. Although cyanobacterial lectins have presented broad biotechnological potential, little research has been directed to Amazonian Cyanobacterial diversity. In order to identify new antiviral lectins, we performed genomic analysis in seven cyanobacterial strains from Coleção Amazônica de Cianobactérias e Microalgas (CACIAM). We found 75 unique CDS presenting one or more lectin domains. Since almost all were annotated as hypothetical proteins, we used homology modeling and molecular dynamics simulations to evaluate the structural and functional properties of three CDS that were more similar to known antiviral lectins. Nostoc sp. CACIAM 19 as well as Tolypothrix sp. CACIAM 22 strains presented cyanovirin-N homologues whose function was confirmed by binding free energy calculations. Asn, Glu, Thr, Lys, Leu, and Gly, which were described as binding residues for cyanovirin, were also observed on those structures. As for other known cyanovirins, those residues in both our models also made favorable interactions with dimannose. Finally, Alkalinema sp. CACIAM 70d presented one CDS, which was identified as a seven-bladed beta-propeller structure with binding sites predicted for sialic acid and N-acetylglucosamine. Despite its singular structure, our analysis suggested this molecule as a new putative antiviral lectin. Overall, the identification and the characterization of new lectins and their homologues are a promising area in antiviral research, and Amazonian cyanobacteria present biotechnological potential to be explored in this regard.

In silico analysis of the cyanobacterial lectin scytovirin: new insights into binding properties.

Scytovirin is a lectin isolated from the cyanobacterium Scytonema varium that has shown activity against HIV, SARS coronavirus and Zaire Ebola virus. Its 95 amino acids are divided into two structural domains (SD), the first spanning amino acids 1-48 (SD1) and the second 49-95 (SD2). Interestingly, the domains are nearly identical but differ in their affinities for carbohydrates. With the aim of enhancing understanding of the binding properties of scytovirin, we performed molecular dynamics (MD) simulations of scytovirin complexed with Man4. We set up three systems: (i) Man4 bound to both domains (SD1 + SD2) using the full-length protein; (ii) Man4 bound to an incomplete protein, containing only SD1 and (iii) Man4 bound to an incomplete protein containing only SD2. Contrary to other reports, binding free energy results suggest that Man4 can bind simultaneously to SD1 and SD2 binding regions, but SD1 individually has the best values of energy and the best affinity for Man4. Decomposition of the binding free energy showed that the residues that interact with Man4 were different in the three systems, suggesting that the binding mechanism of Man4 varies between full-length protein, SD1 and SD2. The results presented here may help to formulate strategies to use scytovirin and promote mutagenesis studies to improve the antiviral activity of scytovirin.

Characterization of mitochondrial genome of Haemagogus janthinomys (Diptera: Culicidae).

Haemagogus janthinomys is a mosquito of high importance in public health due its involvement on natural wild cycles of two important arboviruses in the Brazilian Amazon region: Yellow Fever virus (Flaviviridae, Flavivirus) and Mayaro virus (Togaviridae, Alphavirus). Here, we have sequenced and described all the mitochondrial genes for the Hg. janthinomys species. The complete coding sequence is14 937 bp long and includes 37 functional genes, of which 13 codes for proteins, 22 for tRNA and 2 for ribosomal subunits. Region A + T (control region) is not presented here. The data should be helpful on further taxonomic and evolutionary studies of this important arbovirus vector.

Zika virus in the Americas: Early epidemiological and genetic findings.

Brazil has experienced an unprecedented epidemic of Zika virus (ZIKV), with ~30,000 cases reported to date. ZIKV was first detected in Brazil in May 2015, and cases of microcephaly potentially associated with ZIKV infection were identified in November 2015. We performed next-generation sequencing to generate seven Brazilian ZIKV genomes sampled from four self-limited cases, one blood donor, one fatal adult case, and one newborn with microcephaly and congenital malformations. Results of phylogenetic and molecular clock analyses show a single introduction of ZIKV into the Americas, which we estimated to have occurred between May and December 2013, more than 12 months before the detection of ZIKV in Brazil. The estimated date of origin coincides with an increase in air passengers to Brazil from ZIKV-endemic areas, as well as with reported outbreaks in the Pacific Islands. ZIKV genomes from Brazil are phylogenetically interspersed with those from other South American and Caribbean countries. Mapping mutations onto existing structural models revealed the context of viral amino acid changes present in the outbreak lineage; however, no shared amino acid changes were found among the three currently available virus genomes from microcephaly cases. Municipality-level incidence data indicate that reports of suspected microcephaly in Brazil best correlate with ZIKV incidence around week 17 of pregnancy, although this correlation does not demonstrate causation. Our genetic description and analysis of ZIKV isolates in Brazil provide a baseline for future studies of the evolution and molecular epidemiology of this emerging virus in the Americas.

Pacui Virus, Rio Preto da Eva Virus, and Tapirape Virus, Three Distinct Viruses within the Family Bunyaviridae.

Nearly complete genome sequences for three ungrouped viruses, Pacui virus (BEAN27326), Rio Preto da Eva virus (BEAR540870), and Tapirape virus (BEAN767592) isolated in the Amazon region are reported here. All three genomic segments (small, medium and large RNA) were recovered and were similar to members of the genus Orthobunyavirus.

Draft Genome Sequence of the Brazilian Cyanobium sp. Strain CACIAM 14.

Given the scarcity of data pertaining to whole-genome sequences of cyanobacterial strains isolated in Brazil, we hereby present the draft genome sequence of the Cyanobium sp. strain CACIAM 14, isolated in southeastern Amazonia.