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UNASSIGNED: Intestinal leakage commonly occurs in severe dengue infection with zonulin as a biomarker. The aim of this study was to determine the effects of NS1 on liver weight, zonulin expression and serum zonulin levels.
UNASSIGNED: This laboratory experiment used 18 ddY mice, which were randomly divided into control (C), PBS (T1), and PBS + NS1 (T2) groups. Mice in the T1 and T2 groups were intravenously injected with 500 μl PBS only and 50 μg NS1 respectively. Mice blood samples were collected before and after three-day treatment for measurement of zonulin level. The fresh liver was weighted directly and were then used for immunostaining.
UNASSIGNED: The C group had lower wet liver weight compared to the T groups (p=0.001). Increased expression of liver zonulin was found in the T2 group, significant different from the C (p=0.014) and T1 groups (p=0.020). After treatment, serum zonulin levels in the T1 group was higher than that of the T1 group before treatment (p=0.035) but not in control (p=0.753) and T2 groups (p=0.869).
UNASSIGNED: Administration of 50 μg NS 1 increases wet liver weight and zonulin expression in hepatocytes, but did not increase serum zonulin levels in ddY mice.

BACKGROUND: Dengue infection is caused by an arbovirus with a wide range of presentations, varying from asymptomatic disease to unspecific febrile illness and haemorrhagic syndrome with shock, which can evolve to death. In Brazil, the virus circulates since the 1980s with many introductions of new serotypes, genotypes, and lineages since then. Here we report a fatal case of dengue associated with a Dengue virus (DENV) lineage not detected in the country until now.
METHODS: The patient, a 58-year-old man arrived at the hospital complaining of fever and severe abdominal pain due to intense gallbladder edema, mimicking acute abdomen. After 48 h of hospital admission, he evolved to refractory shock and death. DENV RNA was detected in all tissues collected (heart, lung, brain, kidney, spleen, pancreas, liver, and testis). Viral sequencing has shown that the virus belongs to serotype 2, American/Asian genotype, in a new clade, which has never been identified in Brazil before. The virus was phylogenetically related to isolates from central America [Puerto Rico (2005-2007), Martinique (2005), and Guadeloupe (2006)], most likely arriving in Brazil from Puerto Rico.
CONCLUSIONS: In summary, this was the first fatal documented case with systemic dengue infection associated with the new introduction of Dengue type 2 virus in Brazil during the 2019 outbreak.

The dengue viruses (DENVs) occur throughout tropical and subtropical regions of the world where they infect 100s of millions of people annually. In Australia, the dengue receptive zone is confined to the northern state of Queensland where the principal vector Aedes aegypti (L.) is present. In the current study, two populations of Ae. aegypti from north Queensland were exposed to two urban outbreak strains and one sylvatic strain of dengue virus type 2 (DENV-2). The titer of virus required to infect 50% of mosquitoes was between 105 and 106 50% tissue culture infectious dose (TCID)50/ml and was influenced by the combination of the origin of Ae. aegypti population and virus strain. When exposed to infectious bloodmeal titers > 106 TCID50/ml, infection and dissemination rates were all > 50% and were significantly affected by the origin of the mosquito population but not by the strain of DENV-2. Replication of DENV-2 was also significantly affected by the mosquito population and the titer of the infectious bloodmeal that mosquitoes were exposed to. The results of this study are discussed in the context of DENV transmission dynamics in northern Australia and the relative fitness of the sylvatic virus strain in urban Ae. aegypti populations.

BACKGROUND: Dengue hemorrhagic fever is caused by four serotypes of dengue viruses transmitted by mosquitoes. In Vietnam, dengue outbreaks occur every year, and all four serotypes have been found circulating with the dominant one varying over time. However, in 2017 an unusual dengue fever outbreak occurred in the North of Vietnam, predominantly caused by DENV1 (92%) and DENV2 (7.3%). The objective of the present study was to obtain and characterize the full-length genome sequence of seven DENV2 strains in 2017 epidemic.
METHODS: Whole-genome sequencing of seven DENV2 isolates from the 2017 outbreak were obtained using the Illumina MiSeq next generation sequencer system. Complete genome sequences were then analyzed to find out genetic variants and genetic relationships between these DENV2 with other strains that circulated in Vietnam previously and other regions of the world.
RESULTS: The complete genome sequence of seven DENV2 isolates in the 2017 dengue outbreak comprised 10,696 nucleotides with an open reading frame coding for 3392 amino acids. The genome analysis showed only a small number of amino acid changes which were obtained in all genes, in which a few amino acids substitutions were distributed over the positions such as G156 (NS1), V106 (NS2A), and L258/T260 (NS5). The phylogenetic analysis revealed that the DENV2 isolates in the 2017 outbreak were most closely related to the dengue virus from India in 2006, suggesting that the causative virus originated from the DENV2 that caused dengue hemorrhagic fever in 2006 in India.
CONCLUSIONS: The first complete genome sequences of seven DENV2 isolates in the 2017 dengue outbreak in Northern Vietnam were successfully obtained. The genetic and phylogenetic data indicated that these DENV2 isolates were not causative virus circulating in Vietnam previously but originated from India in 2006. These data are emerging and providing valuable information for the management and surveillance of dengue in Vietnam.

BackgroundWith more than 300 million infections estimated annually worldwide, dengue is the most prevalent arboviral infection. On Reunion Island, after a large outbreak in 1977-78, only limited episodes of viral circulation or sporadic cases were reported till 2015.AimOur objective was to document and report on the circulation of dengue virus after the occurrence of a small outbreak during austral summer 2015/16 and until the large outbreak of 2018.MethodsBeside the mandatory notification of biologically confirmed dengue cases, additional systems of surveillance were set up: estimation of dengue-like syndrome in people seeking care by their family doctor, surveillance of emergency department visits related to dengue, surveillance of hospitalised dengue patients and deaths classifications.ResultsAfter a moderate outbreak during summer 2015/16 with 231 cases, 2017 was characterised by limited viral circulation (97 cases) which, however, persisted during the austral winter. By February 2018, the number of cases had increased and led to a peak at the beginning of May 2018. More than 6,000 cases were reported this year (dengue virus type 2 only). In addition, six deaths of dengue patients were notified.ConclusionIn 2017, the persistence of transmission during winter created favourable conditions for the emergence of an epidemic during summer 2018. After this moderate epidemic wave, the viral circulation persisted during winter 2018 for the second year, opening the door for the second wave in 2019 and for potential endemisation of the disease on Reunion Island in the near future.

We identified dengue in ≈51% of patients given a clinical diagnosis of suspected dengue in Taiz, Yemen, during 2016. The cosmopolitan genotype of dengue virus type 2 was most common; viruses appeared to have originated in Saudi Arabia. Damage to public health infrastructure during the ongoing civil war might enable dengue to become endemic to Yemen.

Dengue virus (DENV) is transmitted by mosquitoes and is a major public health concern. The study of innate mosquito defense mechanisms against DENV have revealed crucial roles for the Toll, Imd, JAK-STAT, and RNAi pathways in mediating DENV in the mosquito. Often overlooked in such studies is the role of intrinsic cellular defense mechanisms that we hypothesize to work in concert with the classical immune pathways to affect organismal defense. Our understanding of the molecular interaction of DENV with mosquito host cells is limited, and we propose to expand upon the recent results from a genome-scale, small interfering RNA (siRNA)-based study that identified mammalian host proteins associated with resistance to dengue/West Nile virus (DENV/WNV) infection. The study identified 22 human DENV/WNV resistance genes (DVR), and we hypothesized that a subset would be functionally conserved in Aedes aegypti mosquitoes, imparting cellular defense against flaviviruses in this species. We identified 12 homologs of 22 human DVR genes in the Ae. aegypti genome. To evaluate their possible role in cellular resistance/antiviral defense against DENV, we used siRNA silencing targeted against each of the 12 homologs in an Ae. aegypti cell line (Aag2) infected with DENV2 and identified that silencing of the two candidates, AeFKBP1 and AeATCAY, homologs of human FKBP1B and ATCAY, were associated with a viral increase. We then used dsRNA to silence each of the two genes in adult mosquitoes to validate the observed antiviral functions in vivo. Depletion of AeFKBP1 or AeATCAY increased viral dissemination through the mosquito at 14 days post-infection. Our results demonstrated that AeFKBP1 and AeATCAY mediate resistance to DENV akin to what has been described for their homologs in humans. AeFKBP1 and AeATCAY provide a rare opportunity to elucidate a DENV-resistance mechanism that may be evolutionarily conserved between humans and Ae. aegypti.

Dengue virus (DENV) emerged from the sylvatic environment and colonized urban settings, being sustained in a human-Aedes-human transmission chain, mainly by the bites of females of the anthropophilic species Aedes aegypti. Herein, we sought evidence for fine-tuning in viral codon usage, possibly due to viral adaptation to human transmission. We compared the codon adaptation of DENV serotype 2 (DENV-2) genotypes from urban and sylvatic habitats and tried to correlate the findings with key evolutionary determinants. We found that DENV-2 codons of urban and sylvatic genotypes had a higher CAI to humans than to Ae. aegypti. Remarkably, we found no significant differences in codon adaptation to human between urban American/Asian and sylvatic DENV-2 genotypes. Moreover, CAI values were significantly different, when comparing all genotypes to Ae. aegypti codon preferences, with lower values for sylvatic than urban genotypes. In summary, our findings suggest the presence of a molecular signature among the genotypes that circulate in sylvatic and urban environments, and may help explain the trafficking of DENV-2 strains to an urban cycle.

Dengue virus type 2 was isolated from a tourist who returned from Borneo to Australia. Phylogenetic analysis identified this virus as highly divergent and occupying a basal phylogenetic position relative to all known human and sylvatic dengue virus type 2 strains and the most divergent lineage not assigned to a new serotype.