Thread by @DrGrimaldesJ

#IDEAS💡
1️⃣ PART

HEMORRHAGIC FEVER DUE TO #DENGUE VIRUS 🦟 MECHANISM #ADE and #MIF
pubmed.ncbi.nlm.nih.gov/36016361/
Antibody Dependent Enhancement (ADE): favorable ″bad″ antibodies for viral infections

pubmed.ncbi.nlm.nih.gov/33123500/
✅Intrinsic ADE: the dark side of antibody-dependent enhancement during dengue infection

The risk of severe dengue disease occurs during secondary infection with a different virus serotype than the previous infection...

...this occurs due to ADE= "Subneutralizing antibodies against virus particles opsonize dengue virus entry by forming complexes immune".
There are 2 types ADE
1)extrinsic ADE 👉improves virus entry
2)intrinsic ADE 👉results in increased virus production through

IFN1 inhibition and IL-10 activation👉 favors Th2-type immune response

Virus > ADE > ⬆️IL10 IL6 > ⬇️IFN IL12 > Th2

pubmed.ncbi.nlm.nih.gov/32506725/
✅Dengue fever, Sars-CoV-2 and ADE

pubmed.ncbi.nlm.nih.gov/32866898/
ADE and hyperinflammation Sars-CoV-2 infection: comparison with dengue hemorrhagic fever and feline infectious peritonitis

ADE has been reported after vaccination or secondary infections with other corona viruses, Ebola and dengue

🎯 The normal thing is that the union of antibodies to viral particles 👉 produces their neutralization.
🔥However, in viruses with monocyte/macrophage tropism such as FCoV, DENV, SC2👉 there will be viraemia if neutralization is not achieved 👉 it will induce a cytokine storm.

pubmed.ncbi.nlm.nih.gov/36371813/
✅ADE and the complement system
Complement-mediated ADE in: DENV, West Nile virus, measles, RSV, HIV, and Ebola.

ADE and complement: ADE binds to viruses 👉C1q binds to this complex and activates the complement cascade 👉

👉recruitment of immune cells 👉secretion of pro-inflammatory cytokines and complement deposition in tissues, forming an obstruction

pubmed.ncbi.nlm.nih.gov/34117329/
Increased ADE correlates with the level of viraemia in patients with dengue

mdpi.com/2076-2607/8/6/…
- Macrophage migration inhibitory factor (#MIF) = pleiotropic proinflammatory cytokine

- The serum level of MIF is positively correlated with the severity of the disease in patients with dengue.

✅Three MIF pathogenic functions in immunoregulatory crosstalk during DENV infection:
(1) Facilitation of DENV replication;
(2) improvement of vascular leakage;
(3) regulation of the immune response.

Dengue > MIF > viral replication by autophagy
🔹MIF > disrupts tight junctions (ZO-1) > altering permeability vascular
🔹MIF > thrombomodulin > altera coagulation factors
 🔹MIF >TNF, IFN-γ, IL-1β, IL-2, IL-6, and IL-8

🎯MINOCYCLINE:
- Blocks DENV autophagy and MIF secretion
- Reduces the production of TNF-α, IL-6, IL-12, IFN-γ and CCL2 through the suppression of NF-κB

mdpi.com/1999-4915/14/8…
Endothelial dysfunction, HMGB1 and dengue

- HMGB1 during the early response of the endothelium to DENV infection.

- HMGB1: promotes viral replication and inflammation

✅Dengue > HMGB1 >NF-kB > inflammation and endothelial hypermability

pubmed.ncbi.nlm.nih.gov/22860034/
Dengue virus infection mediates HMGB1 release > induces vascular leakage in endothelial cells
pubmed.ncbi.nlm.nih.gov/29167501/
Fatal cases of dengue show virus-specific HMGB1 response in peripheral organs

Romulo Daniel Grimaldes Jimenez, MD
Internal Medicine

@DrLBoominathan @LancetMicrobe @NatureMicrobiol @NatureMicrobiol @Nature