Dengue virus

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A Microbial Biorealm page on the genus Dengue virus

Classification

Higher order taxa

Viruses; ssRNA positive-strand viruses; Flaviviridae; Flavivirus; Dengue virus

Description and significance

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 (1). (source: Frontiers in Dengue Virus Research)

Genome structure

The four serotypes of dengue virus are single-stranded positive-sense RNA viruses with a genome of about 11000 bases that codes for three structural proteins, C, prM, E; seven nonstructural proteins, NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5; and short non-coding regions on both the 5' and 3' ends.

Pathology

Dengue is a disease caused by the mosquito-borne dengue viruses. In the last century, dengue has escalated in geographic distribution and disease severity to become now the most common arboviral infection of humans in the subtropical and subtropical regions of the world. 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. According to the World Health Organization (WHO), two fifths of the world population is at risk of dengue virus infection. It has been suggested that globalization and climate change have had a significant impact on the emergence of DENV in new areas (1).

Therapeutic Approaches

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. (source: Frontiers in Dengue Virus Research)

Virus Replication

Replication of all positive-stranded RNA viruses occurs in close association with virus-induced intracellular membrane structures. 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. (source: Frontiers in Dengue Virus Research)

Current Research

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 (1).

The 5' and 3' terminal regions of the viral RNA carry inverted complementary sequences that mediate long-range RNA-RNA interactions and genome cyclization. In the last few years, a great deal has been learned about the mechanisms by which the viral untranslated regions function during DENV replication (1).

The pathogenesis of dengue infection is complicated and, despite intensive research, not well understood. Current research is investigating the burden of disease and the host (age, ethnicity, co-morbidities, immune and genetic factors) and viral (epidemiological and genetic factors) determinants for disease severity (1).

References

1. Hanley, K.A. and Weaver, S.C. 2010. Frontiers in Dengue Virus Research