Overview of latest articles and publications on ebola in PubMed. PubMed is a service of the US National Library of Medicine that includes over 18 million citations from MEDLINE and other life science journals.
- Neotropical bats that co-habit with humans function as dead-end hosts for dengue virus.
Neotropical bats that co-habit with humans function as dead-end hosts for dengue virus. [Journal Article]PLoS Negl Trop Dis 2017 May 18; 11(5):e0005537.PNVicente-Santos A, Moreira-Soto A, Soto-Garita C, et al. Several studies have shown Dengue Virus (DENV) nucleic acids and/or antibodies present in Neotropical wildlife including bats, suggesting that some bat species may be susceptible to DENV infection. Her...Publisher Full TextSeveral studies have shown Dengue Virus (DENV) nucleic acids and/or antibodies present in Neotropical wildlife including bats, suggesting that some bat species may be susceptible to DENV infection. Here we aim to elucidate the role of house-roosting bats in the DENV transmission cycle. Bats were sampled in households located in high and low dengue incidence regions during rainy and dry seasons in Costa Rica. We captured 318 bats from 12 different species in 29 households. Necropsies were performed in 205 bats to analyze virus presence in heart, lung, spleen, liver, intestine, kidney, and brain tissue. Histopathology studies from all organs showed no significant findings of disease or infection. Sera were analyzed by PRNT90 for a seroprevalence of 21.2% (51/241), and by PCR for 8.8% (28/318) positive bats for DENV RNA. From these 28 bats, 11 intestine samples were analyzed by RT-PCR. Two intestines were DENV RNA positive for the same dengue serotype detected in blood. Viral isolation from all positive organs or blood was unsuccessful. Additionally, viral load analyses in positive blood samples by qRT-PCR showed virus concentrations under the minimal dose required for mosquito infection. Simultaneously, 651 mosquitoes were collected using EVS-CO2 traps and analyzed for DENV and feeding preferences (bat cytochrome b). Only three mosquitoes were found DENV positive and none was positive for bat cytochrome b. Our results suggest an accidental presence of DENV in bats probably caused from oral ingestion of infected mosquitoes. Phylogenetic analyses suggest also a spillover event from humans to bats. Therefore, we conclude that bats in these urban environments do not sustain DENV amplification, they do not have a role as reservoirs, but function as epidemiological dead end hosts for this virus.
- Genetic signatures coupled with lineage shift characterize endemic evolution of Dengue virus serotype 2 during 2015 outbreak in Delhi, India.
Genetic signatures coupled with lineage shift characterize endemic evolution of Dengue virus serotype 2 during 2015 outbreak in Delhi, India. [Journal Article]Trop Med Int Health 2017 May 23.TMChoudhary MC, Gupta E, Sharma S, et al. We observed evolution of a distinct lineage of DENV-2 strains on the Indian subcontinent with possible changes in endemic circulating dengue strains that might give rise to more pathogenic strains. Thi...Publisher Full TextIn 2015 New Delhi witnessed a massive outbreak of Dengue virus (DENV) resulting in high morbidity and mortality. We report the molecular characterization of the dominant circulating DENV strain to understand its evolution and dispersal.DENV infections were diagnosed by detection of IgM/NS1 antigen and serotyping was performed by C-PrM PCR. Envelope gene was amplified and variation(s) in envelope gene were analyzed. Phylogenetic tree construction, time-based phylogeny and origin of DENV were analyzed. Site-specific selection pressure of envelope gene variants was analysed.Confirmed DENV infection was observed in 11.34% (32/282) cases while PCR positivity for C-PrM region was observed in 54.16% (13/24) of NS1 antigen-positive cases. All samples belonged to serotype 2 and cosmopolitan genotype. Phylogenetic analysis using envelope gene revealed segregation of cosmopolitan genotype strains into specific lineages. The Indian strains clustered separately forming a distinct monophyletic lineage (lineage III) with a signature amino acid substitution viz., I162V and R288K. Selection pressure analysis revealed that 215D, 288R and 304K, were positively selected sites. The rate of nucleotide substitution was 6.93x10-4 substitutions site-1 year-1 with time to most common ancestor was around 10 years with JX475906 (Hyderabad strain) and JN030345 (Singapore strain) as its most probable ancestor.We observed evolution of a distinct lineage of DENV-2 strains on the Indian subcontinent with possible changes in endemic circulating dengue strains that might give rise to more pathogenic strains. This article is protected by copyright. All rights reserved.
- [Dengue with unusual clinical features in an infant: Case report].
[Dengue with unusual clinical features in an infant: Case report]. [English Abstract, Journal Article]Rev Chil Pediatr 2017 Apr; 88(2):275-279.RCMéndez-Domínguez N, Achach-Medina K, Morales-Gual YM, et al. Dengue fever in young infant infections may be afebrile, so it is important to suspect them appropriately in the presence of a generalised rash, tachycardia, and hypotension, in order to avoid the dead...The state of Yucatan, in Mexico, is an endemic area for dengue. During 2015, there was an unpredicted increase in the number of expected cases of dengue fever.To describe and analyse the clinical presentation, progress, and management of a case of dengue infection with non-specific clinical manifestations in an infant which resulted in a dengue shock syndrome.One month old infant admitted to hospital with a generalised rash and a history of being bitten by an insect. He was diagnosed with anaphylaxis based on clinical manifestations and anamnesis. While in hospital, he developed hypotension, tachycardia, anaemia, and respiratory distress. He was transferred to the intensive care unit, but died on the fifth day. He tested positive to dengue virus in the PCR test and for IgG antibodies using Elisa. The basic cause of death was dengue shock syndrome.Dengue fever in young infant infections may be afebrile, so it is important to suspect them appropriately in the presence of a generalised rash, tachycardia, and hypotension, in order to avoid the deadly consequences of dengue shock.
- Platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue.
Platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue. [Journal Article]PLoS Pathog 2017 May 19; 13(5):e1006385.PPTrugilho MRO, Hottz ED, Brunoro GVF, et al. Dengue is the most prevalent human arbovirus disease worldwide. Dengue virus (DENV) infection causes syndromes varying from self-limiting febrile illness to severe dengue. Although dengue pathophysiolo...Publisher Full TextDengue is the most prevalent human arbovirus disease worldwide. Dengue virus (DENV) infection causes syndromes varying from self-limiting febrile illness to severe dengue. Although dengue pathophysiology is not completely understood, it is widely accepted that increased inflammation plays important roles in dengue pathogenesis. Platelets are blood cells classically known as effectors of hemostasis which have been increasingly recognized to have major immune and inflammatory activities. Nevertheless, the phenotype and effector functions of platelets in dengue pathogenesis are not completely understood. Here we used quantitative proteomics to investigate the protein content of platelets in clinical samples from patients with dengue compared to platelets from healthy donors. Our assays revealed a set of 252 differentially abundant proteins. In silico analyses associated these proteins with key molecular events including platelet activation and inflammatory responses, and with events not previously attributed to platelets during dengue infection including antigen processing and presentation, proteasome activity, and expression of histones. From these results, we conducted functional assays using samples from a larger cohort of patients and demonstrated evidence for platelet activation indicated by P-selectin (CD62P) translocation and secretion of granule-stored chemokines by platelets. In addition, we found evidence that DENV infection triggers HLA class I synthesis and surface expression by a mechanism depending on functional proteasome activity. Furthermore, we demonstrate that cell-free histone H2A released during dengue infection binds to platelets, increasing platelet activation. These findings are consistent with functional importance of HLA class I, proteasome subunits, and histones that we found exclusively in proteome analysis of platelets in samples from dengue patients. Our study provides the first in-depth characterization of the platelet proteome in dengue, and sheds light on new mechanisms of platelet activation and platelet-mediated immune and inflammatory responses.
- A conformational switch high-throughput screening assay and allosteric inhibition of the flavivirus NS2B-NS3 protease.
A conformational switch high-throughput screening assay and allosteric inhibition of the flavivirus NS2B-NS3 protease. [Journal Article]PLoS Pathog 2017 May 25; 13(5):e1006411.PPBrecher M, Li Z, Liu B, et al. The flavivirus genome encodes a single polyprotein precursor requiring multiple cleavages by host and viral proteases in order to produce the individual proteins that constitute an infectious virion. P...Publisher Full TextThe flavivirus genome encodes a single polyprotein precursor requiring multiple cleavages by host and viral proteases in order to produce the individual proteins that constitute an infectious virion. Previous studies have revealed that the NS2B cofactor of the viral NS2B-NS3 heterocomplex protease displays a conformational dynamic between active and inactive states. Here, we developed a conformational switch assay based on split luciferase complementation (SLC) to monitor the conformational change of NS2B and to characterize candidate allosteric inhibitors. Binding of an active-site inhibitor to the protease resulted in a conformational change of NS2B and led to significant SLC enhancement. Mutagenesis of key residues at an allosteric site abolished this induced conformational change and SLC enhancement. We also performed a virtual screen of NCI library compounds to identify allosteric inhibitors, followed by in vitro biochemical screening of the resultant candidates. Only three of these compounds, NSC135618, 260594, and 146771, significantly inhibited the protease of Dengue virus 2 (DENV2) in vitro, with IC50 values of 1.8 μM, 11.4 μM, and 4.8 μM, respectively. Among the three compounds, only NSC135618 significantly suppressed the SLC enhancement triggered by binding of active-site inhibitor in a dose-dependent manner, indicating that it inhibits the conformational change of NS2B. Results from virus titer reduction assays revealed that NSC135618 is a broad spectrum flavivirus protease inhibitor, and can significantly reduce titers of DENV2, Zika virus (ZIKV), West Nile virus (WNV), and Yellow fever virus (YFV) on A549 cells in vivo, with EC50 values in low micromolar range. In contrast, the cytotoxicity of NSC135618 is only moderate with CC50 of 48.8 μM on A549 cells. Moreover, NSC135618 inhibited ZIKV in human placental and neural progenitor cells relevant to ZIKV pathogenesis. Results from binding, kinetics, Western blot, mass spectrometry and mutagenesis experiments unambiguously demonstrated an allosteric mechanism for inhibition of the viral protease by NSC135618.
- Elevation as a proxy for mosquito-borne Zika virus transmission in the Americas.
Elevation as a proxy for mosquito-borne Zika virus transmission in the Americas. [Journal Article]PLoS One 2017; 12(5):e0178211.PlosWatts AG, Miniota J, Joseph HA, et al. These results suggest low potential for mosquito-borne ZIKV transmission above 2,000m in the Americas. Although elevation is a crude predictor of environmental suitability for ZIKV transmission, its co...When Zika virus (ZIKV) first began its spread from Brazil to other parts of the Americas, national-level travel notices were issued, carrying with them significant economic consequences to affected countries. Although regions of some affected countries were likely unsuitable for mosquito-borne transmission of ZIKV, the absence of high quality, timely surveillance data made it difficult to confidently demarcate infection risk at a sub-national level. In the absence of reliable data on ZIKV activity, a pragmatic approach was needed to identify subnational geographic areas where the risk of ZIKV infection via mosquitoes was expected to be negligible. To address this urgent need, we evaluated elevation as a proxy for mosquito-borne ZIKV transmission.For sixteen countries with local ZIKV transmission in the Americas, we analyzed (i) modelled occurrence of the primary vector for ZIKV, Aedes aegypti, (ii) human population counts, and (iii) reported historical dengue cases, specifically across 100-meter elevation levels between 1,500m and 2,500m. Specifically, we quantified land area, population size, and the number of observed dengue cases above each elevation level to identify a threshold where the predicted risks of encountering Ae. aegypti become negligible.Above 1,600m, less than 1% of each country's total land area was predicted to have Ae. aegypti occurrence. Above 1,900m, less than 1% of each country's resident population lived in areas where Ae. aegypti was predicted to occur. Across all 16 countries, 1.1% of historical dengue cases were reported above 2,000m.These results suggest low potential for mosquito-borne ZIKV transmission above 2,000m in the Americas. Although elevation is a crude predictor of environmental suitability for ZIKV transmission, its constancy made it a pragmatic input for policy decision-making during this public health emergency.
- wMel limits zika and chikungunya virus infection in a Singapore Wolbachia-introgressed Ae. aegypti strain, wMel-Sg.
wMel limits zika and chikungunya virus infection in a Singapore Wolbachia-introgressed Ae. aegypti strain, wMel-Sg. [Journal Article]PLoS Negl Trop Dis 2017 May 19; 11(5):e0005496.PNTan CH, Wong PJ, Li MI, et al. Our results showed that wMel limits both ZIKV and CHIKV infection when introgressed into a Singapore Ae. aegypti genetic background. These results also strongly suggest that female Aedes aegypti carryi...Publisher Full TextZika (ZIKV) and Chikungunya (CHIKV) viruses are emerging Aedes-borne viruses that are spreading outside their known geographic range and causing wide-scale epidemics. It has been reported that these viruses can be transmitted efficiently by Ae. aegypti. Recent studies have shown that Ae. aegypti when transinfected with certain Wolbachia strains shows a reduced replication and dissemination of dengue (DENV), Chikungunya (CHIKV), and Yellow Fever (YFV) viruses. The aim of this study was to determine whether the wMel strain of Wolbachia introgressed onto a Singapore Ae. aegypti genetic background was able to limit ZIKV and CHIKV infection in the mosquito.Five to seven-day old mosquitoes either infected or uninfected with wMel Wolbachia were orally infected with a Ugandan strain of ZIKV and several outbreak strains of CHIKV. The midgut and salivary glands of each mosquito were sampled at days 6, 9 and 13 days post infectious blood meal to determine midgut infection and salivary glands dissemination rates, respectively. In general, all wild type Ae. aegypti were found to have high ZIKV and CHIKV infections in their midguts and salivary glands, across all sampling days, compared to Wolbachia infected counterparts. Median viral titre for all viruses in Wolbachia infected mosquitoes were significantly lower across all time points when compared to wild type mosquitoes. Most significantly, all but two and one of the wMel infected mosquitoes had no detectable ZIKV and CHIKV, respectively, in their salivary glands at 14 days post-infectious blood meal.Our results showed that wMel limits both ZIKV and CHIKV infection when introgressed into a Singapore Ae. aegypti genetic background. These results also strongly suggest that female Aedes aegypti carrying Wolbachia will have a reduced capacity to transmit ZIKV and CHIKV.
- Dengue and acute kidney injury: A need for aggressive maneuvers.
Dengue and acute kidney injury: A need for aggressive maneuvers. [Letter]Saudi J Kidney Dis Transpl 2017 May-Jun; 28(3):667-669.SJMallhi TH, Khan AH, Khan YH, et al.
- Natural regulatory anticoagulants proteins among Sudanese patients with dengue virus infection.
Natural regulatory anticoagulants proteins among Sudanese patients with dengue virus infection. [Journal Article]Int J Health Sci (Qassim) 2017 Apr-Jun; 11(2):3-8.IJBashir BA, Saeed OKA The findings of this study suggest that lower levels of these proteins in patients with dengue are attributed to disseminated intravascular coagulation.Abnormalities in natural physiologic anticoagulants are observed in dengue infection. Laboratory values such as protein C (PC), protein S (PS), and antithrombin (AT) indicate this problem on the coagulation system in dengue. Recently, an interrelationship between dengue and the levels of natural anticoagulants has been observed.The study conducted to find out the effect of dengue on the natural anticoagulant proteins.A case-control study was conducted in Port Sudan Teaching Hospital from February 2013 to June 2014 for 334 cases of dengue caused by dengue virus, 217 (65%) males and 117 (35%) were females along with 101 cases of control 64 (63.4%) males and 37 (36.6%) were females. Laboratory-positive dengue cases were confirmed by immunoglobulin (Ig) M and IgG immune chromatography rapid test and the WHO criteria were used for classifying the dengue severity. Platelet count (PLT), plasma prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, D-dimer (DD), aspartate transaminase, alanine transaminase, PC, PS, and AT were performed.Of 334, 289 patients had dengue fever (DF) and 45 patients had dengue hemorrhagic fever (DHF). Thrombocytopenia was present in 279 (83.5%). PLT was found to be significantly low in the case of dengue (P < 0.000). There was a highly significant difference between the prolongations of PT and PTT in DF (P < 0.000). Prolongations of PT and PTT were significantly higher (90% and 76.2%, respectively) in DF than DHF patients (10% and 23.8%, respectively). PC and PS were significantly higher in DHF 100% and 80% than DF 89% and 57%, respectively.The findings of this study suggest that lower levels of these proteins in patients with dengue are attributed to disseminated intravascular coagulation.
- Uncovering the repertoire of endogenous flaviviral elements in Aedes mosquito genomes.
Uncovering the repertoire of endogenous flaviviral elements in Aedes mosquito genomes. [Journal Article]J Virol 2017 May 24.JVSuzuki Y, Frangeul L, Dickson LB, et al. Endogenous viral elements derived from non-retroviral RNA viruses were described in various animal genomes. Whether they have a biological function such as host immune protection against related viruse...Publisher Full TextEndogenous viral elements derived from non-retroviral RNA viruses were described in various animal genomes. Whether they have a biological function such as host immune protection against related viruses is a field of intense study. Here, we investigated the repertoire of endogenous flaviviral elements (EFVEs) in Aedes mosquitoes, the vectors of arboviruses such as dengue and chikungunya viruses. Previous studies identified three EFVEs from Ae. albopictus and one from Ae. aegypti cell lines. However, in-depth characterization of EFVEs in wild-type mosquito populations and individuals in vivo has not been performed. We detected the full-length DNA sequence of the previously described EFVEs and their respective transcripts in several Ae. albopictus and Ae. aegypti populations from geographically distinct areas. However, EFVE-derived proteins were not detected by mass spectrometry. Using deep sequencing, we detected the production of piRNA-like small RNAs in antisense orientation, targeting the EFVEs and their flanking regions in vivo The EFVEs were integrated in repetitive regions of the mosquito genomes, and their flanking sequences varied among mosquito populations from different geographical regions. We bioinformatically predicted several new EFVEs from a Vietnamese Ae. albopictus population and observed variation in the occurrence of those elements among mosquito populations. Phylogenetic analysis of an Ae. aegypti EFVE suggested that it integrated prior to the global expansion of the species and subsequently diverged among and within populations. Together, this study revealed substantial structural and nucleotide diversity of flaviviral integrations in Aedes genomes. Unraveling this diversity will help to elucidate the potential biological function of these EFVEs.IMPORTANCE Endogenous viral elements (EVEs) are whole or partial viral sequences integrated in host genomes. Interestingly, some EVEs have important functions for host fitness and antiviral defense. Because mosquitoes also have EVEs in their genomes, characterizing these EVEs is a prerequisite for their potential use to manipulate the mosquito antiviral response. Here, we focused on EVEs related to the Flavivirus genus, to which dengue and Zika viruses belong, in Aedes mosquito individuals from geographically distinct areas. We showed the existence in vivo of flaviviral EVEs previously identified in mosquito cell lines and we detected new ones. We showed that EVEs have evolved differently in each mosquito population. They produced transcripts and small RNAs, but not proteins, suggesting a function at the RNA level. Our study uncovers the diverse repertoire of flaviviral EVEs in Aedes mosquito populations and contributes to understand their role in the host antiviral system.