Dengue Virus: Infection, Immunological Response, and Vaccine Development

Abstract

In the tropics and subtropics climates worldwide, the dengue virus (DENV) is the most common of arboviruses and a significant public health threat. The severe disease usually occurs during the primary infection, but more serious cases begin after the second instance of infection with a different serotype. Humans' innate immune system is composed of monocytes, macrophages, and dendritic cells, and they are capable of mounting rapid inflammatory responses. These cells are also called primary antigen-presenting cells, and they are essential for the formation of the immune system's long-term memory mechanisms. Through scientific advances, valuable knowledge into the pathogenesis of more serious diseases, and new methods to the production of dengue vaccines and antiviral drugs have been provided. We summarized details in the current literature review, including references, abstracts, and full text of journal articles. So that, we tried to review all available studies that projected existing awareness about the immune response to the dengue virus and the current status of the vaccine. Such information was selected and extracted from the PubMed, Web of Science, and Google Scholar databases for published data from 2000 to 2020 using relevant keywords containing a combination of terms, including dengue fever, epidemiology, clinical manifestation, immune response, and vaccine.

Dengue Virus Infection: A Tale of Viral Exploitations and Host Responses

“…Studies have confirmed the role of Sphingosine kinase (SK1) in the TNF-α-mediated elicitation of inflammation via NFκB [ 53 , 54 ]. Netosis or NET (Neutrophil extracellular traps) formation by neutrophils is an interesting feature observed in patients suffering from Dengue Hemorrhagic Fever (DHF), with evidence of dire nuclei decondensation [ 55 , 56 ]. Other strategies employing microRNAs (miRNAs) to alleviate the severe inflammatory conditions in DENV patients are being explored.…”

“…Neutrophils are also recruited to the primary site of infection by the tissue-resident macrophages through the secretion of IL-8, TNF-α, and IFN-β. Antiviral factors such as TNF-α and defensins are generated by neutrophils [ 55 ]. Moreover, the degree of complement activation by the DENV-NS1 protein is greater in DHF patients than in mild/intermediate Dengue Fever (DF) [ 73 ].…”

“…These responses prompt the CD8+ T cytotoxic cells to secrete perforins and granzymes and the CD4+ T cells to involve in Th1 (secreting IFN-γ and TNF-α) effector functions. Moreover, the other T cell subsets such as the Treg cells act to regulate inflammation via TGF-β and IL-10, and the Follicular T cells function to aid the B cells into generating highly specific antibodies with sufficient affinity [ 55 , 80 ]. Although the entire immune system works together to put up a prodigious fight against DENV, some of these responses may in turn cause host damage, through an event known as the “cytokine storm”.…”

In silico analysis of anti-dengue activity of faloak (Sterculia quadrifida R. Br) stem bark compounds

“…Dengue virus (DENV) is a single-stranded positive RNA virus that has a round virion with a size of 50 nm consisting of three structural proteins, namely capsid (C), pre-membrane/membrane (prM/M), and envelope (E), and seven nonstructural proteins (NS), namely NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5, which are directly involved in assembly and replication of DENV (Sindi, 2021). Protein E and NS5 can be used as targets for dengue infection.…”