Dengue virus compartmentalization during antibody-enhanced infection

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Secondary dengue virus (DENV) infection with a different serotype increases severe dengue risk through antibody-dependent enhancement (ADE).
• During ADE, non-neutralizing antibodies opsonize DENV, enhancing viral entry into immune cells via Fc-gamma receptors (FcγRs).
• Previous work showed leukocyte immunoglobulin-like receptor-B1 (LILRB1) co-ligation by antibody-opsonized DENV recruits SHP-1 phosphatase to reduce interferon-stimulated gene induction.

Purpose of the Study:

• To investigate the role of LILRB1 signaling in the intracellular trafficking and survival of antibody-opsonized DENV.
• To determine how LILRB1 co-ligation impacts phagolysosomal acidification and DENV's evasion of cell-autonomous immunity.

Main Methods:

• Investigated the signaling pathway involving LILRB1, SHP-1, and phagolysosomal acidification in immune cells exposed to antibody-opsonized DENV.
• Assessed the trafficking of antibody-opsonized DENV to phagolysosomal compartments.
• Evaluated the impact of LILRB1 signaling on intracellular DENV survival.

Main Results:

• LILRB1 signaling, via SHP-1, attenuates the rapid acidification of phagolysosomes following FcγR-mediated uptake of antibody-opsonized DENV.
• Antibody-opsonized DENV shows reduced or slower trafficking to lytic phagolysosomal compartments.
• Co-ligation of LILRB1 enhances intracellular DENV survival by enabling evasion of cell-autonomous immune responses.

Conclusions:

• LILRB1 plays a critical role in facilitating DENV immune evasion by modulating phagolysosomal maturation and acidification.
• Targeting phagosome acidification pathways may offer therapeutic strategies against DENV and similar viruses.
• Understanding LILRB1's function provides insights into severe dengue pathogenesis and potential antiviral interventions.