Human cytomegalovirus US28 allows dendritic cell exit from lymph nodes

Area of Science:

• Virology
• Immunology
• Cell Biology

Background:

• Human cytomegalovirus (HCMV) infects blood-borne dendritic cells (DCs).
• HCMV expresses the US28 viral G protein-coupled receptor (GPCR).
• The role of US28 in HCMV colonization and systemic spread remained unclear.

Purpose of the Study:

• To investigate the function of the HCMV US28 GPCR in dendritic cell (DC) biology.
• To determine if US28 contributes to host colonization by promoting DC recirculation.
• To explore the potential of targeting US28 signaling to control HCMV infection.

Main Methods:

• Comparative analysis of HCMV US28 and murine CMV (MCMV) M33 GPCR functions.
• In vitro studies assessing DC recirculation and extravasation.
• Investigation of G protein-dependent signaling pathways.

Main Results:

• HCMV US28, similar to MCMV M33, promotes dendritic cell (DC) recirculation.
• This US28-mediated DC recirculation facilitates HCMV systemic infection.
• MCMV M33 also enhances systemic infection by promoting infected DC extravasation.

Conclusions:

• The HCMV US28 GPCR plays a crucial role in promoting DC recirculation, a mechanism that supports viral systemic spread.
• Targeting US28 G protein-dependent signaling presents a potential therapeutic strategy to reduce HCMV systemic infection.
• Understanding viral GPCR functions in immune cell trafficking is key to controlling viral pathogenesis.