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Published on: July 6, 2013
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Murine Cytomegalovirus Spreads by Dendritic Cell Recirculation
Helen E Farrell1,2, Kimberley Bruce3, Clara Lawler3
1School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia h.farrell1@uq.edu.au.
Mbio
|October 5, 2017
Summary
Murine cytomegalovirus (MCMV) spreads through dendritic cells (DC) recirculating from lymph nodes into the blood, bypassing traditional routes. This virus-driven DC recirculation, dependent on viral M33 and host CD44, offers new targets for limiting cytomegalovirus (CMV) infections.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Herpesviruses, including cytomegaloviruses (CMVs), have coevolved with hosts for millions of years, exploiting host cell biology.
- Systemic dissemination of CMVs is hypothesized to originate from infected bone marrow stem cells, but evidence is limited.
- Understanding early host colonization events is crucial for preventing human cytomegalovirus (HCMV) disease.
Purpose of the Study:
- To identify alternative pathways for murine cytomegalovirus (MCMV) systemic spread beyond stem cell infection.
- To investigate the mechanism of MCMV dissemination following mucosal entry.
- To elucidate host and viral factors involved in MCMV-infected dendritic cell (DC) migration and lymph node (LN) egress.
Main Methods:
- Tracking MCMV colonization in mice after intranasal infection.
- Analyzing the migration patterns of infected CD11c+ dendritic cells (DCs) from the lungs to lymph nodes, blood, and salivary glands.
- Investigating the role of host factor CD44 and viral factor M33 in DC egress from lymph nodes.
Main Results:
- Intranasal MCMV infection led to lung DCs migrating sequentially to lymph nodes, blood, and salivary glands.
- Replication-deficient MCMV utilized the same DC migration pathway, indicating dissemination does not require viral replication.
- MCMV-infected DCs exited lymph nodes via high endothelial venules, a novel pathway dependent on CD44 and the viral M33 chemokine receptor.
- Impaired LN exit due to absence of CD44 or M33 resulted in reduced systemic spread.
Conclusions:
- Virus-driven dendritic cell recirculation from lymph nodes into the blood represents a previously unrecognized pathway for systemic cytomegalovirus spread.
- The viral M33 chemokine receptor and host CD44 are critical for MCMV-infected DCs to exit lymph nodes and enter the bloodstream.
- Targeting viral chemokine receptors like M33 could be a strategy to prevent systemic CMV infections.
