Dengue Virus

Dengue virus (DENV) is a single, positive-stranded mRNA virus (Baltimore classification Group IV) belonging to the family Flaviviridae and is the cause of dengue fever. DENV is transmitted through mosquito bites in tropical and sub-tropical climates, and is estimated to infect up to 400 million people globally per year[1]. DENV is subdivided into serotypes 1, 2, 3, and 4 as distinct antigenic variants, although these serotypes have been shown to share degrees of antigenic overlap[2]. DENV infection can trigger processes such as autophagy, the ER stress response, or even apoptosis, resulting in symptoms ranging from mild headache, fatigue, and muscle soreness to severe nausea, vomiting, intense shooting pain (particularly behind the eye), and high fever. In its most severe form, DENV infection can cause hemorrhagic fever and rapid onset of death.

Symptom severity is linked to re-infection or co-infection with chikungunya or zika virus [3]. In the case of re-infection by an alternate DENV serotype, the process of antibody-dependent enhancement is thought to facilitate viral infection, whereby sub-optimal antibody recognition of a DENV antigen does not neutralize the virus, but instead acts as a Trojan horse to promote viral entry and replication through the hijacking of the FcγR pathway.

To date, no prophylactic (direct antiviral) treatment exists against DENV. In 2019, Dengvaxia by Sanofi-Pasteur was approved by the U.S. FDA as a four-serotype DENV vaccine, although its efficacy varies between 42.3% - 77.7% depending on the infecting serotype [4].

[1] Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Vector-Borne Diseases (DVBD), July 14, 2020
[2] L. C. Katzelnick, J. M. Fonville, G. D. Gromowski, J. B. Arriaga, A. Green, S. L. James, L. Lau, M. Montoya, C. Wang, L. A. VanBlargan, C. A. Russell, H. M. Thu, T. C. Pierson, P. Buchy, J. G. Aaskov, J. L. Munoz-Jordan, N. Vasilakis, R. V. Gibbons, R. B. Tesh, A. D. M. E. Osterhaus, R. A. M. Fouchier, A. Durbin, C. P. Simmons, E. C. Holmes, E. Harris, S. S. Whitehead, D. J. Smith. Dengue viruses cluster antigenically but not as discrete serotypes. Science, 2015; 349 (6254): 1338
[3] Vogels CBF, Rückert C, Cavany SM, Perkins TA, Ebel GD, Grubaugh ND (2019) Arbovirus coinfection and co-transmission: A neglected public health concern? PLoS Biol 17(1): e3000130.
[4] First FDA-approved vaccine for the prevention of dengue disease in endemic regions