Quasispecies of dengue virus

Abstract

Pathogenic viruses have RNA genomes that cause acute and chronic infections. These viruses replicate with high mutation rates and exhibit significant genetic diversity, so-called viral quasispecies. Viral quasispecies play an important role in chronic infectious diseases, but little is known about their involvement in acute infectious diseases such as dengue virus (DENV) infection. DENV, the most important human arbovirus, is a causative agent of dengue fever (DF) and dengue hemorrhagic fever (DHF). Accumulating observations suggest that DENV exists as an extremely diverse virus population, but its biological significance is unclear. In other virus diseases, quasispecies affect the therapeutic strategies using drugs and vaccines. Here, I describe the quasispecies of DENV and discuss the possible role of quasispecies in the pathogenesis of and therapeutic strategy against DENV infection in comparison with other viruses such as Hepatitis C virus, human immunodeficiency virus type 1, and poliovirus.

Keywords: Neutralization; Primary infection; Secondary infection; Serotype; antibody-dependent enhancement; immune response.

Fig. 1.

A) Diversity of pre-existing antibodies and DENV. In DENV-infected patients with secondary infection, the diverse antibody population and the diverse DENV population exist at a very early stage of infection. B) Pre-existing neutralizing antibodies block DENV infection. On the other hand, non-neutralizing antibodies enhance DENV infection through ADE. DENV infection is positively and negatively regulated by pre-existing antibodies.

Fig. 2.

Hypothetical mechanism of DENV infection. DENV present as a heterogenous population at an early phase of infection. The parts of DENV are positively selected by non-neutralizing/enhancing antibodies. Homogenous DENV population is predominantly produced at the peak of infection.