Soluble NS1 Antagonizes IgG- and IgA- Mediated Monocytic Phagocytosis of DENV Infected Cells.

Abstract

Dengue virus (DENV) is endemic in >100 countries, infecting an estimated 400 million individuals every year. Infection with DENV raises an antibody response primarily targeting viral structural proteins. However, DENV encodes several immunogenic nonstructural (NS) proteins, one of which, NS1, is expressed on the membrane of DENV-infected cells. IgG and IgA isotype antibodies that bind NS1 are abundant in serum following DENV infection. Our study aimed to determine if NS1-binding IgG and IgA isotype antibodies contribute to the clearance of DENV-infected cells by antibody-mediated cellular phagocytosis. We observed that both IgG and IgA isotype antibodies can facilitate monocytic uptake of DENV NS1-expressing cells in an FcγRI- and FcαRI-dependent fashion. Interestingly, this process was antagonized by the presence of soluble NS1, suggesting that the production of soluble NS1 by infected cells may serve as immunological chaff, antagonizing opsonization and clearance of DENV-infected cells.

• Authors: Mitchell J Waldran, Adam D Wegman, Lauren E Bahr, Nathan H Roy, Jeffrey R Currier, Adam T Waickman
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 228 Issue 1 Pg. 70-79 (06 28 2023) ISSN: 1537-6613 [Electronic] United States
• PMID: 37103221 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Immunoglobulin G
• Immunoglobulin A
• Viral Nonstructural Proteins
• Antibodies, Viral

Topics

• Humans
• Dengue
• Dengue Virus
• Phagocytosis
• Immunoglobulin G
• Immunoglobulin A (metabolism)
• Viral Nonstructural Proteins (metabolism)
• Antibodies, Viral