Dengue is currently endemic in more than one hundred countries around the world. It causes approximately 50-100 million infections annually, including 250,000-500,000 cases of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). According to the World Health Organization (WHO), two fifths of the world population is at risk of dengue virus (DENV) infection.

It has been suggested that globalization and climate change have had a significant impact on the emergence of DENV in new areas. No vaccine or therapy against DENV is currently approved for use in humans, and alternative strategies to control DENV infection are urgently needed, particularly because the design of such strategies may also inform efforts in vaccine design.

Current research focuses on the prophylaxis/therapeutic potential of monoclonal antibodies (MAbs) against DENV and the challenges to implementation of this strategy, including antibody-dependent enhancement (ADE), genetic variability of DENV strains, potential for selection of MAb escape variants, and financial cost. Also important are the recent immunologic and structural studies that have provided a new understanding of antibody-mediated neutralization mechanisms and protection against DENV and other flavivirus infections. These insights are having an important impact on the development of vaccines and antibody-based therapies.

from Ana P. Goncalvez, Robert H. Purcell, and Ching-Juh Lai in Frontiers in Dengue Virus Research

Further reading: Dengue Virus

Labels: dengue, dengue fever, dengue virus

Dengue has emerged as the most common mosquito-borne viral disease of humans in the past three decades. There are no available vaccines or antivirals against DENV. Currently, vector control is the only method for prevention of the disease. Development of a successful vaccine would require for it to be effective against all four DENV serotypes, economical, and provide long-term protection. Antivirals directed against one or more stages of the virus life cycle are likely to form an important part of dengue disease therapeutics. The strategies that have been used in the past towards development of an effective antiviral against dengue, as well as those being employed currently are discussed in light of information from structural biology, computational biology and molecular virology, highlighting the potential opportunities and obstacles to their use.

from Mayuri, Elisa La Bauve and Richard J. Kuhn in Frontiers in Dengue Virus Research

Further reading: Dengue Virus

Labels: dengue, dengue fever, Dengue therapy, Dengue vaccine, dengue virus

A safe and effective vaccine for the control of Dengue Virus disease is urgently needed and long overdue. Because each of the four dengue virus serotypes can cause the full spectrum of dengue disease, vaccination must protect against each serotype. An unprecedented number of vaccine candidates are in development and under clinical evaluation, with live attenuated vaccines being the most advanced. Considerable effort is also being made in the development of inactivated, subunit protein, virus vectored, and DNA vaccine candidates. The need to elicit protective immunity without predisposing for antibody-mediated enhanced disease, the need for rapid and tetravalent protection, and the need for an economical vaccine have presented challenges in the development pathway. Nevertheless, innovative research and development continues to provide solutions to these obstacles.

from Stephen S. Whitehead and Anna P. Durbin in Frontiers in Dengue Virus Research

Further reading: Dengue Virus

Labels: dengue, dengue fever, dengue virus, Dengue Virus Vaccine

Dengue/dengue hemorrhagic fever is the most important vector-borne viral disease globally, with over half of the world's population living at risk of infection. While vaccines for other flaviviruses such as yellow fever, Japanese encephalitis and tick-borne encephalitis have been developed, dengue vaccine development is complicated by the need to incorporate all four virus serotypes into a single formulation. The only way to prevent dengue transmission presently is to reduce the vector population. Research focuses on the latest information on mosquito-dengue virus interaction, with the overall goal of identifying areas of research where improved understanding would likely contribute to our ability to predict and prevent cyclical epidemics.

from Eng-Eong Ooi and Duane J. Gubler in Frontiers in Dengue Virus Research

Further reading: Dengue Virus

Labels: dengue, dengue fever, dengue virus

Dengue Virus (DENV) produces a wide range of human illness, ranging from asymptomatic infections to hemorrhagic and potentially fatal disease. Severe disease is associated with high viremia, immune enhancement of sequential infections, and exacerbated inflammatory response.

DENV is sensed in mammalian cells by endosomal and cytoplasmic receptors and stimulates the type-1 interferon (IFNα/ β) response. Secreted IFNα/ β stimulates JAK/STAT signaling, which results in the activation of IFNα/ β- stimulated genes that lead the infected cells toward the establishment of an antiviral response. Genomic technology has enabled the identification of a remarkable list of genes induced in human host cells in response to DENV infection. The results define antiviral and pro-inflammatory responses mainly composed of IFNα/ β- induced genes, which likely participate in the regulation of the immune response and vascular leakage during acute illness. DENV counteracts the IFNα/ β response of the host.

The evidence indicates that non-structural proteins of DENV weaken IFNα/ β signaling, causing reduced activation of IFNα/ β-induced genes. The increased virus uptake, weakened host cell defense, and unrestrained inflammatory response likely predispose patients to develop severe illness. The unveiling of these virus-host interactions leads to a better understanding of dengue pathogenesis, and to innovative diagnostic and therapeutic approaches.

from Jorge L. Muñoz-Jordán and Irene Bosch in Frontiers in Dengue Virus Research

Further reading: Dengue Virus

Labels: dengue, dengue fever, dengue virus

As for all plus-stranded RNA viruses, dengue virus (DENV) genomic RNA is infectious. Transfection of full length DENV RNA genome into a susceptible cell triggers a complete cycle of viral replication. Construction of cDNA clones together with reverse genetics has proven to be a valuable tool to uncover genetic determinants of viral replication and to understand the function of the viral untranslated regions (UTRs).

Translation initiation and initiation of RNA synthesis occur at the 5' and 3' terminal regions of the genome, respectively, and rely on complex RNA-RNA and RNA- protein interactions. The DENV 5'UTR contains two defined RNA structures, Stem-Loop A and Stem-Loop B, which have distinct functions during the process of viral RNA synthesis. The viral 3'UTR contains three domains with conserved sequences and structures. In these domains, there are RNA elements that are essential for the replication process and other elements that act as enhancers of the process.

The 5' and 3' terminal regions of the viral RNA also carry inverted complementary sequences that mediate long-range RNA-RNA interactions and genome cyclization. It has been demonstrated for dengue and other flaviviruses that the circular conformation of the genome is a crucial determinant for viral replication.

In the last few years, a great deal has been learned about the mechanisms by which the viral UTRs function during DENV replication.

from Andrea Gamarnik in Frontiers in Dengue Virus Research

Further reading: Dengue Virus

Labels: dengue, dengue fever, dengue virus

Replication of all positive-stranded RNA viruses investigated so far occurs in close association with virus-induced intracellular membrane structures. Dengue virus (DENV), as a member of the family Flaviviridae, also induces such extensive rearrangements of intracellular membranes, called replication complex (RC). These RCs seem to contain viral proteins, viral RNA and host cell factors. However, the biogenesis of the RC and the three-dimensional organisation is to the most part unclear.

from Sven Miller, Ines Romero-Brey, and Ralf Bartenschlager in Frontiers in Dengue Virus Research

Further reading: Dengue Virus

Labels: dengue, dengue fever, dengue virus, Flaviviridae

Positive strand RNA viruses, including flaviviruses, generally utilize the translational machinery of the host to synthesize viral proteins either in a cap-dependent or cap-independent manner to produce polyprotein precursors which are then processed into mature proteins. Polyprotein processing is accomplished by the concerted action of host and viral proteases. While some viruses, such as the hepatitis C virus code for more than one protease to perform distinct functions, flaviviruses code for a novel two-component serine protease which participates in early and late stages of the viral life cycle.

from R. Padmanabhan and Alex Y. Strongin in Frontiers in Dengue Virus Research

Further reading: Dengue Virus

Labels: dengue, dengue fever, dengue virus, flavivirus, Flaviviruses

Dengue virus (DENV), a mosquito-borne flavivirus, is the causative agent of dengue fever, currently one of the most significant emerging disease challenges to global public health. Although dengue is an old disease, recent decades have seen an unprecedented increase in the geographic range, incidence, and severity of infection. The virus infects 100 million people annually and is endemic in many tropical and sub-tropical regions in the world.

At present, neither a licensed vaccine nor anti-viral drugs are available to control dengue disease, prompting a plethora of research initiatives aimed at understanding the molecular and cellular virology, genomics, and evolution of this important virus.

Further reading: Frontiers in Dengue Virus Research

Labels: dengue, dengue disease, dengue fever, dengue virus, DENV, flavivirus