Compared with “type”:”entrez-nucleotide”,”attrs”:”text”:”MT180479″,”term_id”:”1820400125″,”term_text”:”MT180479″MT180479 strain, amino acid substitutions were identified in 165 sites throughout the complete coding region of the 5 DENV-2 isolates in this study (Table 3). isolated from serum and/or CSF samples of 3 patients. The highest viral genome levels were detected in the CSF and serum of the patient who succumbed to the illness. A phylogenetic tree revealed that the DENV-2 isolates belonged to a new clade of cosmopolitan genotype and were genetically close to strains identified in China, South Korea, Singapore, Malaysia, Thailand, and the Philippines. According to the NGS analysis, greater frequencies of nonsynonymous and synonymous mutations per gene were identified in the nonstructural genes. The full genomes of serum- and CSF-derived DENV-2 from the same patient shared 99.7% similarity, indicating that the virus spread across the blood-brain barrier. This is the first report to describe neurotropic DENV-2 using whole-genome analysis and to provide the clinical, immunological, and virological characteristics of dengue encephalitis patients during a severe dengue outbreak in Sri Lanka in 2017. Introduction Dengue is one of the most globally prevalent, arthropod-borne, viral diseases in humans [1]. The overall incidence of dengue, as well as the incidence of explosive dengue outbreaks, has increased dramatically over the last several years [2]. The causative agent, dengue virus (DENV), which includes four distinct, but closely related serotypes, belongs to the genus in the family [3]. Transmitted by mosquitoes, dengue virus Squalamine lactate occurs primarily in tropical and subtropical areas of the world [4]. The infection causes a flu-like illness, and patients occasionally develop potentially lethal complications. The different degrees of dengue severity were re-categorized in 2009 2009 by Squalamine lactate the World Health Organization (WHO) into dengue without warning signs (DwoWS), dengue with warning signs (DwWS), and severe dengue (SD) [5]. The annual incidence of dengue infections was estimated to be 400 million per year, of which approximately 96 million were clinically apparent [2]. Death occurs in about 2.5% of dengue-infected people [2, 3]. In recent years, there has been an increase in the number of reported cases of neurological manifestations associated with dengue infections. However, the precise incidence rate of neurological symptoms remains unclear [6]. Neurological signs were first reported in 1976 as atypical symptoms of dengue infection, Mouse monoclonal to CD68. The CD68 antigen is a 37kD transmembrane protein that is posttranslationally glycosylated to give a protein of 87115kD. CD68 is specifically expressed by tissue macrophages, Langerhans cells and at low levels by dendritic cells. It could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cellcell and cellpathogen interactions. It binds to tissue and organspecific lectins or selectins, allowing homing of macrophage subsets to particular sites. Rapid recirculation of CD68 from endosomes and lysosomes to the plasma membrane may allow macrophages to crawl over selectin bearing substrates or other cells. and their incidence rates have varied from 0.5% to 20% in recent years [7, 8]. Neurological complications associated with DENV infection include encephalopathy (caused by hepatic failure or metabolic disorders), encephalitis (caused by direct viral invasion), neuromuscular complications (Guillain-Barre syndrome or transient muscle dysfunctions), and neuro-ophthalmic involvement [9]. In addition, other less common neurological features have been described as atypical manifestation of dengue infection. Dengue serotypes 2 and 3 are most commonly associated with neurological symptoms [10, 11]. Confirmed dengue cases with neurological manifestations have been confirmed by assessing the presence of the virus and/or antibody in the cerebrospinal fluid (CSF) [6, 12]. However, molecular and biological characterizations of neurotropic DENV strains have been extremely limited, despite their important roles in the neuropathogenesis of dengue. In 2017, Squalamine lactate the largest dengue outbreak was reported in Sri Lanka, with over 185,000 clinical cases and at least 250 fatal cases [13]. The age distribution of infected individuals showed that many patients were young people (15C39 years age group) [13]. Atypical manifestations of DENV infection, i.e. dengue encephalitis, were reported during this outbreak. The aims of our study were to describe the neurotropic DENV-2 strains that we isolated from CSF and serum samples of pediatric and adult patients with dengue encephalitis during the severe dengue outbreak in Sri Lanka, in 2017 and to provide medical, immunological, and virological characteristics of these individuals. Materials and methods Ethics statement Honest approvals for this study were provided by the Institution Honest Committee on Medical Study and Review, General Hospital (Teaching) Kandy, Sri Lanka (THK/ERC/73/2017) and the Institute of Tropical Medicine Honest Committee, Nagasaki University or college, Japan (180608200). Sample collection Combined serum and CSF samples used in this study were from five confirmed DEN individuals between March 2017- January 2018. These individuals included children ( .
