Dengue virus

About: Dengue virus is a research topic. Over the lifetime, 12671 publications have been published within this topic receiving 461406 citations. The topic is also known as: DENV.

Recombinant Dengue virus protein NS2B alters membrane permeability in different membrane models.

Abstract: One of the main phenomena occurring in cellular membranes during virus infection is a change in membrane permeability. It has been observed that numerous viral proteins can oligomerize and form structures known as viroporins that alter the permeability of membranes. Previous findings have identified such proteins in cells infected with Japanese encephalitis virus (JEV), a member of the same family that Dengue virus (DENV) belongs to (Flaviviridae). In the present work, we investigated whether the small hydrophobic DENV protein NS2B serves a viroporin function. We cloned the DENV NS2B sequence and expressed it in a bacterial expression system. Subsequently, we evaluated the effect of DENV NS2B on membranes when NS2B was overexpressed, measured bacterial growth restriction, and evaluated changes of permeability to hygromycin. The NS2B protein was purified by affinity chromatography, and crosslinking assays were performed to determine the presence of oligomers. Hemolysis assays and transmission electron microscopy were performed to identify structures involved in permeability changes. The DENV-2 NS2B protein showed similitude with the JEV viroporin. The DENV-2 NS2B protein possessed the ability to change the membrane permeability in bacteria, to restrict bacterial cell growth, and to enable membrane permeability to hygromycin B. The NS2B protein formed trimers that could participate in cell lysis and generate organized structures on eukaryotes membranes. Our data suggest that the DENV-2 NS2B viral protein is capable of oligomerizing and organizing to form pore-like structures in different lipid environments, thereby modifying the permeability of cell membranes.

Advances in dengue diagnosis.

Abstract: Despite improvements in health, epidemics of infectious diseases continue to occur, and new diseases emerge and old diseases reemerge (113). Mosquito-borne flavivirus diseases are currently considered reemerging infections because of the increase in the incidences of yellow fever and, mainly, dengue fever and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) observed in the last few years (30, 86). The dengue syndrome is an acute febrile viral exanthem, accompanied by headache, myalgia, anorexia, gastrointestinal disturbances, and postration, caused by viruses transmitted by mosquitoes (43). DHF is a severe febrile disease characterized by abnormalities of hemostasis and increased vascular permeability. DSS is the result of a hypovolemic shock observed in some DHF cases. DHF/DSS represents the severe form of dengue fever (52). The disease is caused by any one of the four distinct serotypes (1 to 4) of the dengue virus (52, 114). These viruses are members of the family Flaviviridae; they have a common morphology and genomic structure, and all members share common antigenic determinants. The four dengue virus serotypes are classified as a complex on the basis of clinical, biological, and immunological criteria. Dengue virus complex-specific antigenic determinants have been demonstrated by using neutralization assays, which also can differentiate the dengue virus complex into four antigenically distinct dengue virus serotypes, since each serotype presents a type-specific determinant (49, 52). The flaviviruses are transmitted by mosquitoes of the Stegomia family, mainly Aedes aegypti, a domestic, day-biting mosquito that prefers to feed on humans (52, 99). This is a highly urbanized mosquito, breeding in water stored for domestic use or collected rainwater. A jungle cycle has been proposed to exist in Southeast Asia, since there is a high rate of dengue transmission among different species of monkeys (52, 105). The genomic RNA of dengue viruses is single stranded and approximately 11 kb in length. The RNA is infectious and, as in the rest of the flaviviruses, it has a single open reading frame (103). The order of proteins encoded in the long open reading frame is 59-C-prM(M)-E-NS1-NS2A-NS2B-NS3-NS4A-NS4BNS5-39. The mature virion contains three structural proteins: C, the nucleocapside or core protein of 13.5 kDa; M, a membrane-associated protein of 8 kDa; and the E (envelope) protein of 51 kDa. The E protein has the sites for viral attachment to and transport through host cell plasma membranes. Functional domains responsible for the neutralization and hemagglutination of goose erythrocytes are associated with the E protein. It contains epitopes specific for serotype, dengue complex, and group (6, 48, 103, 115). Considering the technology currently used for the diagnosis of dengue viruses, a case definition in which laboratory confirmation is emphasized has been proposed. The laboratory criteria for confirmation of the infection and the disease include the isolation of dengue virus from serum and/or autopsy samples, the demonstration of a fourfold or greater increase in the titer of immunoglobulin G (IgG) or IgM antibody to one or more dengue virus antigens in paired serum samples, or the demonstration of dengue virus antigen in autopsy tissue or serum samples by immunohistochemistry, by immunofluorescence, or by the detection of the viral nucleic acid (98).

Maternal antibody and viral factors in the pathogenesis of dengue virus in infants.

Abstract: The pathogenesis of dengue in infants is poorly understood. We postulated that dengue severity in infants would be positively associated with markers of viral burden and that maternally derived, neutralizing anti-dengue antibody would have decayed before the age at which infants with dengue presented to the hospital. In 75 Vietnamese infants with primary dengue, we found significant heterogeneity in viremia and NS1 antigenemia at hospital presentation, and these factors were independent of disease grade or continuous measures of disease severity. Neutralizing antibody titers, predicted in each infant at the time of their illness, suggested that the majority of infants (65%) experienced dengue hemorrhagic fever when the maternally derived neutralizing antibody titer had declined to <1 : 20. Collectively, these data have important implications for dengue vaccine research because they suggest that viral burden may not solely explain severe dengue in infants and that neutralizing antibody is a reasonable but not absolute marker of protective immunity in infants.

Epidemiology and Clinical Features of Imported Dengue Fever in Europe: Sentinel Surveillance Data from TropNetEurop

Abstract: Travelers have the potential both to acquire and to spread dengue virus infection. The incidence of dengue fever (DF) among European travelers certainly is underestimated, because few centers use standardized diagnostic procedures for febrile patients. In addition, DF is currently not reported in most European public health systems. Surveillance has commenced within the framework of a European Network on Imported Infectious Disease Surveillance (TropNetEurop) to gain information on the quantity and severity of cases of dengue imported into Europe. Descriptions of 294 patients with DF were analyzed for epidemiological information and clinical features. By far the most infections were imported from Asia, which suggests a high risk of DF for travelers to that region. Dengue hemorrhagic fever occurred in 7 patients (2.4%) all of whom recovered. Data reported by member sites of the TropNetEurop can contribute to understanding the epidemiology and clinical characteristics of imported DF.

Emerging Theme: Cellular PDZ Proteins as Common Targets of Pathogenic Viruses

Abstract: More than a decade ago, three viral oncoproteins, adenovirus type 9 E4-ORF1, human T-lymphotropic virus type 1 Tax, and high-risk human papillomavirus E6, were found to encode a related carboxyl-terminal PDZ domain-binding motif (PBM) that mediates interactions with a select group of cellular PDZ proteins. Recent studies have shown that many other viruses also encode PBM-containing proteins that bind to cellular PDZ proteins. Interestingly, these recently recognized viruses include not only some with oncogenic potential (hepatitis B virus, rhesus papillomavirus, cottontail rabbit papillomavirus) but also many without this potential (influenza virus, Dengue virus, tick-borne encephalitis virus, rabies virus, severe acute respiratory syndrome coronavirus, human immunodeficiency virus). Examination of the cellular PDZ proteins that are targets of viral PBMs reveals that the viral proteins often interact with the same or similar types of PDZ proteins, most notably Dlg1 and other members of the membrane-associated guanylate kinase protein family, as well as Scribble. In addition, cellular PDZ protein targets of viral PBMs commonly control tight junction formation, cell polarity establishment, and apoptosis. These findings reveal a new theme in virology wherein many different virus families encode proteins that bind and perturb the function of cellular PDZ proteins. The inhibition or perturbation of the function of cellular PDZ proteins appears to be a widely used strategy for viruses to enhance their replication, disseminate in the host, and transmit to new hosts.