Dengue Virus Infection with Highly Neutralizing Levels of Cross-Reactive Antibodies Causes Acute Lethal Small Intestinal Pathology without a High Level of Viremia in Mice

Journal of Virology
Satoru WatanabeSubhash G Vasudevan

Abstract

Severe dengue virus (DENV)-associated diseases can occur in patients who have preexisting DENV antibodies (Abs) through antibody-dependent enhancement (ADE) of infection. It is well established that during ADE, DENV-antibody immune complexes (ICs) infect Fcγ receptor-bearing cells and increase the systemic viral burden that can be measured in the blood. For protection against infection with DENV serotypes 1 to 4, strongly neutralizing Abs must be elicited to overcome the effect of ADE. Clinical observations in infants who have maternal DENV Abs or recent phase II/III clinical trials with a leading tetravalent dengue vaccine suggested a lack of correlation between Ab neutralization and in vivo disease prevention. In addressing this gap in knowledge, we found that inoculation of ICs formed with serotype cross-reactive Abs that are more than 98% neutralized in vitro promotes high mortality in AG129 mice even though peak viremia was lower than that in direct virus infection. This suggests that the serum viremia level is not always correlated with disease severity. We further demonstrated that infection with the ICs resulted in increased vascular permeability, specifically in the small intestine, accompanied with increased tissue vi...Continue Reading

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Citations

Jan 23, 2016·Antiviral Research·Guntur Fibriansah, Shee-Mei Lok
Nov 22, 2015·Indian Journal of Pediatrics·Rakesh Lodha, Sushil K Kabra
Aug 26, 2015·Antiviral Research·Kitti Wing Ki ChanSubhash G Vasudevan
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Aug 8, 2018·The Journal of Infectious Diseases·Satoru WatanabeSubhash G Vasudevan
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Jun 28, 2019·Science Translational Medicine·Kitti Wing Ki ChanSubhash G Vasudevan
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Nov 17, 2020·Frontiers in Cellular and Infection Microbiology·Rahul ShuklaNavin Khanna
Jun 26, 2021·Frontiers in Immunology·Abhay P S RathoreAshley L St John

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Antibody-Dependent Enhancement

Antibody-dependent enhancement of viral infection is the entry of virus into host cells mediated by antiviral antibodies interacting with Fc or complement receptors. This has been most extensively observed with the dengue virus. Find the latest research on antibody-dependent enhancement here.