Intrinsic ADE: The Dark Side of Antibody Dependent Enhancement During Dengue Infection

Narayan, Rohan; Tripathi, Shashank

doi:10.3389/fcimb.2020.580096

Cited by 95 publications

(92 citation statements)

References 45 publications

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“…These virus-immune complexes facilitate virus entry and enhanced virus replication in the FcγR (fragment crystallizable gamma receptors)-bearing cells, such as monocytes, dendritic cells and macrophages. The internalized DENV particles then initiate an immune cascade which results in the evasion of innate immunity, such as the inhibition of type-1 interferon, and subsequently leads to vascular leakage and severe disease [40,41]. Further, cytokine levels are also assumed to be elevated in secondary dengue infection [42].…”

Section: Discussionmentioning

confidence: 99%

Clinical predictors of severe dengue: a systematic review and meta-analysis

et al. 2021

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Background Severe dengue is a life-threatening complication; rapid identification of these cases, followed by adequate management is crucial to improve the clinical prognosis. Therefore, this study aimed to identify risk factors and predictors of severe dengue. Methods A literature search for studies reporting risk factors of severe dengue among individuals with dengue virus infection was conducted in PubMed, Scopus and Web of Science database from inception to December 31, 2020. Pooled odds ratios (ORs) for patients’ demographic characteristics, co-morbidities, and warning signs were estimated using an inverse variance heterogeneity model. Results We included 143 articles in the meta-analysis from a total of 13 090 articles retrieved from the literature search. The risk factors of severe dengue were: being a child [OR = 1.96; 95% confidence interval (CI): 1.22–3.13], secondary infection (OR = 3.23; 95% CI: 2.28–4.57), and patients with pre-existing diabetes (OR = 2.88; 95% CI: 1.72–4.81) and renal disease (OR = 4.54; 95% CI: 1.55–13.31). Warning signs strongly associated with severe disease were increased haematocrit with a concurrent decrease in platelet count (OR = 5.13; 95% CI: 1.61–16.34), abdominal pain (OR = 2.00; 95% CI: 1.49–2.68), lethargy (OR = 2.73; 95% CI: 1.05–7.10), vomiting (OR = 1.80; 95% CI: 1.43–2.26), hepatomegaly (OR = 5.92; 95% CI: 3.29–10.66), ascites (OR = 6.30; 95% CI: 3.75–10.60), pleural effusion (OR = 5.72; 95% CI: 3.24–10.10) and melena (OR = 4.05; 95% CI: 1.64–10.00). Conclusions Our meta-analysis identified children, secondary infection, diabetes and renal disease(s) as important predictors of severe dengue. Our finding also supports the predictive ability of the WHO warning signs to identify severe dengue. These findings are useful for clinicians to identify severe dengue for management and timely interventions.

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Section: Discussionmentioning

confidence: 99%

Clinical predictors of severe dengue: a systematic review and meta-analysis

et al. 2021

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“…Increased risk of severe disease occurs during secondary infection with a virus serotype distinct from that of prior dengue infection. This occurs by antibody dependent enhancement (ADE) of infection, wherein sub-neutralizing antibodies against the virus particles opsonize dengue virus entry via formation of immune complexes that interact with fragment crystallizable gamma receptors (FcγR) on monocytes, dendritic cells, and macrophages [ 16 , 17 ]. At the beginning of the 21st century, multiple cases of dengue virus concurrent infection with different serotypes have been reported frequently in many places [ 18 ].…”

Section: General Information Of Flavivirus and The Infected Diseasesmentioning

confidence: 99%

Flavivirus: From Structure to Therapeutics Development

Zhao

Wang

Cao

et al. 2021

Life

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Flaviviruses are still a hidden threat to global human safety, as we are reminded by recent reports of dengue virus infections in Singapore and African-lineage-like Zika virus infections in Brazil. Therapeutic drugs or vaccines for flavivirus infections are in urgent need but are not well developed. The Flaviviridae family comprises a large group of enveloped viruses with a single-strand RNA genome of positive polarity. The genome of flavivirus encodes ten proteins, and each of them plays a different and important role in viral infection. In this review, we briefly summarized the major information of flavivirus and further introduced some strategies for the design and development of vaccines and anti-flavivirus compound drugs based on the structure of the viral proteins. There is no doubt that in the past few years, studies of antiviral drugs have achieved solid progress based on better understanding of the flavivirus biology. However, currently, there are no fully effective antiviral drugs or vaccines for most flaviviruses. We hope that this review may provide useful information for future development of anti-flavivirus drugs and vaccines.

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“…Antibody-dependent enhancement (ADE) is a phenomenon by which antibodies elicited from a previous infection facilitate viral entry into a susceptible cell through the engagement of Fc gamma receptors (FcɣRs) (1, 2). The most established example of ADE in humans occurs between the four serotypes of dengue virus (DENV), a mosquito-transmitted flavivirus that is estimated to causẽ 390 million infections annually around the globe (3,4). Studies show that while primary infections with DENV are typically mild, secondary infections with a heterotypic DENV serotype are more frequently severe, with increased incidence of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) (5,6).…”

Section: Introductionmentioning

confidence: 99%

Evaluating the Safety of West Nile Virus Immunity During Congenital Zika Virus Infection in Mice

et al. 2021

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Antibody-dependent enhancement (ADE) is a phenomenon that occurs when cross-reactive antibodies generated from a previous flaviviral infection increase the pathogenesis of a related virus. Zika virus (ZIKV) is the most recent flavivirus introduced to the Western Hemisphere and has become a significant public health threat due to the unanticipated impact on the developing fetus. West Nile virus (WNV) is the primary flavivirus that circulates in North America, and we and others have shown that antibodies against WNV are cross-reactive to ZIKV. Thus, there is concern that WNV immunity could increase the risk of severe ZIKV infection, particularly during pregnancy. In this study, we examined the extent to which WNV antibodies could impact ZIKV pathogenesis in a murine pregnancy model. To test this, we passively transferred WNV antibodies into pregnant Stat2-/- mice on E6.5 prior to infection with ZIKV. Evaluation of pregnant dams showed weight loss following ZIKV infection; however, no differences in maternal weights or viral loads in the maternal brain, spleen, or spinal cord were observed in the presence of WNV antibodies. Resorption rates, and other fetal parameters, including fetal and placental size, were similarly unaffected. Further, the presence of WNV antibodies did not significantly alter the viral load or the inflammatory response in the placenta or the fetus in response to ZIKV. Our data suggest that pre-existing WNV immunity may not significantly impact the pathogenesis of ZIKV infection during pregnancy. Our findings are promising for the safety of implementing WNV vaccines in the continental US.

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Intrinsic ADE: The Dark Side of Antibody Dependent Enhancement During Dengue Infection

Cited by 95 publications

References 45 publications

Clinical predictors of severe dengue: a systematic review and meta-analysis

Clinical predictors of severe dengue: a systematic review and meta-analysis

Flavivirus: From Structure to Therapeutics Development

Evaluating the Safety of West Nile Virus Immunity During Congenital Zika Virus Infection in Mice

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