Pathogenesis of dengue: challenges to molecular biology

Abstract

Dengue viruses occur as four antigenically related but distinct serotypes transmitted to humans by Aedes aegypti mosquitoes. These viruses generally cause a benign syndrome, dengue fever, in the American and African tropics, and a severe syndrome, dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), in Southeast Asian children. This severe syndrome, which recently has also been identified in children infected with the virus in Puerto Rico, is characterized by increased vascular permeability and abnormal hemostasis. It occurs in infants less than 1 year of age born to dengue-immune mothers and in children 1 year and older who are immune to one serotype of dengue virus and are experiencing infection with a second serotype. Dengue viruses replicate in cells of mononuclear phagocyte lineage, and subneutralizing concentrations of dengue antibody enhance dengue virus infection in these cells. This antibody-dependent enhancement of infection regulates dengue disease in human beings, although disease severity may also be controlled genetically, possibly by permitting and restricting the growth of virus in monocytes. Monoclonal antibodies show heterogeneous distribution of antigenic epitopes on dengue viruses. These epitopes serve to regulate disease: when antibodies to shared antigens partially neutralize heterotypic virus, infection and disease are dampened; enhancing antibodies alone result in heightened disease response. Further knowledge of the structure of dengue genomes should permit rapid advances in understanding the pathogenetic mechanisms of dengue.

Recent Epidemiological Trends of Dengue in the French Territories of the Americas (2000–2012): A Systematic Literature Review

“…Further studies to understand the role of ethnicity on the dynamics and severity of dengue in the FTA would be informative in these populations of mixed ethnicity. Collection of seroprevalence data would be useful, as secondary DENV infections are a known risk factor for severe disease [56].…”

Convergent Antibody Signatures in Human Dengue

“…Key determinants of dengue pathogenesis include pre-existing host immunity from prior infection(s) with a distinct DENV serotype and differential virulence of the infecting DENV strain (Halstead and Yamarat, 1965; Messer et al, 2003; Rico-Hesse et al, 1997). Enhanced pathogenicity in sequential DENV infections may be due to sub-optimal immune responses contributed by pre-existing memory B and T cells that were primed by viral antigens from the first infection rather than the naïve B and T cells primed during the current infection (Halstead, 1988, 2009; Peiris and Porterfield, 1979; Rothman and Ennis, 1999). In addition, cytokines released by immune effector cells can play dual roles in attenuating and/or exacerbating disease pathogenesis in dengue (Avirutnan et al, 2007; Rothman and Ennis, 1999).…”

Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity

“…Whereas many questions remain unanswered about the unusual biology and disease spectrum of this flavivirus, there is urgency in determining whether antibodies against other flaviviruses could enhance ZIKV replication and disease pathogenesis. Antibody-dependent enhancement (ADE) of different dengue virus (DENV) serotypes has been shown to correlate with increased viremia and disease severity (2–4). ZIKV is phylogenetically related to other flaviviruses, such as DENV and West Nile virus (WNV), which cocirculate with ZIKV in many regions across the globe.…”