# Genetic Susceptibility of Antibody-dependent Enhancement of Flaviviruses

> **NIH NIH R21** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $211,252

## Abstract

PROJECT SUMMARY:
Antibody-dependent enhancement (ADE) is a phenomenon characteristic of some flavivirus infections and best
known to occur between the four DENV serotypes in humans, but may also occur between sequential DENV,
then ZIKV infections (or vice versa). ADE occurs when subneutralizing levels of antibodies raised against one
flavivirus infection cross-react to enhance a closely related flavivirus infection. ADE is entirely dependent on
the binding of IgG antibodies to FcRs found on susceptible cells, such as monocytes/macrophages. In
humans, there is a nonsynonymous polymorphism that occurs in the FcRIIA gene (rs1801274) that leads to
an arginine (Arg) to histadine (His) change at position 131 that has been shown to alter the affinity of this
receptor for IgG antibodies. We hypothesize that individuals homozygous for the FcRIIA encoding for the high
affinity His allele are at higher risk for developing ADE of flaviviruses than individuals homozygous for the low
affinity Arg allele. In this application, we will test this using K562 cells homozygous for the Arg131 or the
His131 allele as well as primary human monocytes stratified based on genotype to test how this SNP impacts
ADE of flaviviruses in vitro (Aim 1). Using two flavivirus-specific monoclonal antibody clones that we found to
enhance flavivirus infection in K562 cells, we will generate IgG subclass switch variants (IgG1, IgG2, IgG3, or
IgG4) to determine the relative contribution of each IgG subclass in mediating ADE of flaviviruses (Aim 2).

## Key facts

- **NIH application ID:** 9944452
- **Project number:** 5R21AI147141-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Jean Kyou Lim
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $211,252
- **Award type:** 5
- **Project period:** 2019-06-05 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944452

## Citation

> US National Institutes of Health, RePORTER application 9944452, Genetic Susceptibility of Antibody-dependent Enhancement of Flaviviruses (5R21AI147141-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9944452. Licensed CC0.

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