[1] Nevertheless, the mainstream scientific community's understanding of dengue virus may be simplistic as, rather than distinct antigenic groups, a continuum appears to exist.

[7] Additionally, coinfection with and lack of rapid tests for Zika virus and chikungunya complicate matters in real-world infections.

[8] Dengue virus has increased dramatically within the last 20 years, becoming one of the worst mosquito-borne human pathogens that tropical countries have to deal with.

[12][13] The global spread of dengue virus, however, has followed its emergence from sylvatic cycles and the primary lifecycle now exclusively involves transmission between humans and Aedes mosquitoes.

[29][30] Attempts to provide detailed summaries of the life cycle of dengue at the cellular level are published in review articles from different research groups.

[42] Recombinant domains of the E protein are used as well-defined antigens in the serological detection of antibodies directed against dengue virus and as immunogens in vaccine candidates.

[43][44][45] The DENV prM (membrane) protein, which is important in the formation and maturation of the viral particle, consists of seven antiparallel β-strands stabilized by three disulfide bonds.

The immature virion starts out with the E and prM proteins forming 90 heterodimers that give a spiky exterior to the viral particle.

This immature viral particle buds into the endoplasmic reticulum and eventually travels via the secretory pathway to the Golgi apparatus.

This pr peptide acts like a cap, covering the hydrophobic fusion loop of the E protein until the viral particle has exited the cell.

The catalytic triad (His-51, Asp-75 and Ser-135) is found between these two β-barrels, and activity is dependent on the presence of a 43 amino acid segment of the NS2B cofactor.

The DENV RdRp is similar to other RdRps containing palm, finger, and thumb subdomains and a GDD motif for incorporating nucleotides.

[35] Crystal structures of complexes between antibodies and either the ectodomain (sE) of the viral E protein or its domain 3 (ED3) have helped understand the molecular bases of the virus recognition and neutralization.

[60][61] Signs and symptoms may include severe headache; retro-orbital pain; muscle, joint, and bone pain; macular or maculopapular rash; and minor hemorrhagic manifestations, including petechiae, ecchymosis, purpura, epistaxis, bleeding gums, hematuria, or a positive tourniquet test result.

[65] In recent years, many studies have shown that flaviviruses, especially dengue virus, has the ability to inhibit the innate immune response during the infection.

[68] Furthermore, the innate immune system's response to the virus is further damped as expression of interferon-stimulating gene(s) (ISG) is restricted by the aforementioned 'NS4B' protein.

The mosquito's saliva was thought to make the virus spread faster due to the weakened immune response of its host.

[76] The immune responses of antibodies that are trying to fight off the foreign virus actually increase transmission and make the infection worse.

These antibodies inhibit the function of D7 proteins, which enhance transmission of dengue virus[citation needed].

Although immune responses against D7 proteins might impair their antiviral activity, a study showed that non-DENV subjects have slightly higher anti-D7 IgG levels than infected ones, although it was not statistically significant.

[78][79] On 5 December 2022 the European Medicines Agency approved Qdenga, a live tetravalent attenuated vaccine for adults, adolescents and children from four years of age.

[80][58] Dengvaxia has been approved in 11 countries (Mexico, the Philippines, Indonesia, Brazil, El Salvador, Costa Rica, Paraguay, Guatemala, Peru, Thailand, and Singapore).

In September 2014, the Sanofi-Pasteur CEO gave early results of the phase III trial efficacy study in Latin America.

The full analysis of data from the phase III Latin American-Caribbean study will be reviewed by external experts before being published in a peer-reviewed scientific journal.

Primary results has to be presented at the American Society of Tropical Medicine and Hygiene Annual Meeting, held November 2–6, 2014, in New Orleans.

[3] In late 2015 and early 2016, the first dengue vaccine, Dengvaxia (CYD-TDV) by Sanofi-Pasteur, was registered in several countries for use in individuals 9–45 years of age living in endemic areas.

[88][89] One drug, Balapiravir, a repurposed hepatitis C NS5 polymerase inhibitor progressed to a Phase II clinical trial before being stopped due to lack of efficacy.

One drug, Balapiravir, initially repurposed as a hepatitis C NS5 polymerase inhibitor, reached Phase II clinical trials but was stopped due to lack of efficacy.

[92] The journal explores a novel approach by examining the potential of metal-TPI complexes (with iron, cobalt, and zinc) as inhibitors of dengue virus replication.