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Review
. 2023 Jan 15:324:199018.
doi: 10.1016/j.virusres.2022.199018. Epub 2022 Dec 7.

Dengue virus infection - a review of pathogenesis, vaccines, diagnosis and therapy

Boon Hui Kok  1 , Hui Ting Lim  1 , Chin Peng Lim  1 , Ngit Shin Lai  1 , Chiuan Yee Leow  2 , Chiuan Herng Leow  3
Affiliations
Review

Dengue virus infection - a review of pathogenesis, vaccines, diagnosis and therapy

Boon Hui Kok et al. Virus Res. .

Abstract

The transmission of dengue virus (DENV) from an infected Aedes mosquito to a human, causes illness ranging from mild dengue fever to fatal dengue shock syndrome. The similar conserved structure and sequence among distinct DENV serotypes or different flaviviruses has resulted in the occurrence of cross reaction followed by antibody-dependent enhancement (ADE). Thus far, the vaccine which can provide effective protection against infection by different DENV serotypes remains the biggest hurdle to overcome. Therefore, deep investigation is crucial for the potent and effective therapeutic drugs development. In addition, the cross-reactivity of flaviviruses that leads to false diagnosis in clinical settings could result to delay proper intervention management. Thus, the accurate diagnostic with high specificity and sensitivity is highly required to provide prompt diagnosis in respect to render early treatment for DENV infected individuals. In this review, the recent development of neutralizing antibodies, antiviral agents, and vaccine candidates in therapeutic platform for DENV infection will be discussed. Moreover, the discovery of antigenic cryptic epitopes, principle of molecular mimicry, and application of single-chain or single-domain antibodies towards DENV will also be presented.

Keywords: Cross reaction; DENV; Development; Diagnostic; Therapeutic.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig 1
Fig. 1
Global dengue epidemic in 2020 and 2021. The affected countries include Bangladesh, Philippines, Vietnam, India, Maldives, Indonesia, Singapore, Colombia, Paraguay, Peru, Kenya, Fiji, Cook Islands, Reunion Islands, Sri Lanka, Thailand, Sudan, Mauritania, Timor-Leste, Yemen, Nepal, Mayotte, Ecuador and Brazil. Info adapted from (CDC, 2021; ECDC, 2021; WHO, 2021).
Fig 2
Fig. 2
Diagram of DENV genome and NS1 protein domains. Viral genome undergoes translation to generate single polyprotein. After the polyprotein processing, viral proteins are produced via proteolytic cleavages (Fernandez-Garcia et al., 2009). For NS1, the 3 domain regions involving in DENV pathogenesis include β-roll, wing domain and β-ladder (Scaturro et al., 2015).
Fig 3
Fig. 3
Different mechanisms of antibody dependent enhancement (ADE). Viral entry can be facilitated through different pathways with the help of (A) Fc receptors or (B) C1q receptors to be endocytosed into the cell membrane and further causing ADE.
Fig 4
Fig. 4
The level of NS1, IgM and IgG for primary and secondary dengue infection. (A) During primary infection, NS1 and IgM are detectable starting day 0 onwards and day 3 onwards, respectively, while IgG can only be detected on day 10 onwards. (B) For secondary infection, IgG level is used to differentiate both primary and secondary infection by presenting very significant level during acute phase due to rapid anamnestic IgG reaction.
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