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Early Viral Entry Assays for the Identification and Evaluation of Antiviral Compounds
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Early Viral Entry Assays for the Identification and Evaluation of Antiviral Compounds

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Cytomegalovirus host entry and spread

Helen E Farrell1, Philip G Stevenson1

  • 1School of Chemistry and Molecular Biosciences and Child Health Research Centre, University of Queensland, Brisbane, Australia.

The Journal of General Virology
|February 8, 2019
PubMed

Insights

Murine cytomegalovirus (MCMV) uses olfactory neurons for entry and dendritic cells (DCs) for systemic spread. Human cytomegalovirus (HCMV) may use similar pathways involving viral G protein-coupled receptors for immune cell trafficking.

Area of Science:

  • Virology
  • Immunology
  • Mammalian Pathogenesis

Background:

  • Cytomegaloviruses (CMVs) are widespread mammalian pathogens causing significant disease, particularly human cytomegalovirus (HCMV) in congenital infections.
  • Effective control strategies for HCMV are hampered by poorly understood mechanisms of viral entry and spread in naive hosts.
  • Studying related viruses in other mammals, like murine cytomegalovirus (MCMV), can offer crucial insights into conserved pathogenic processes.

Purpose of the Study:

  • To elucidate the distinct mechanisms of CMV entry and systemic dissemination in a mammalian model.
  • To investigate the role of viral G protein-coupled receptors (GPCRs) in mediating immune cell migration and viral spread.
  • To explore potential conserved pathways between MCMV and HCMV for therapeutic targeting.

Main Methods:

  • Comparative analysis of CMV entry routes, focusing on olfactory neurons and heparan binding.
  • Tracking the systemic spread of MCMV via infected dendritic cells (DCs) through lymph nodes (LNs) and high endothelial venules (HEVs).
  • Investigating the function of MCMV M33 and HCMV US28 viral GPCRs in DC migration and viral dissemination.

Main Results:

  • MCMV utilizes olfactory neurons for initial host entry, binding to heparan displayed on neuronal cilia.
  • MCMV-infected DCs migrate from olfactory LNs to circulation via HEVs, a process dependent on the M33 viral GPCR.
  • The HCMV US28 GPCR can functionally substitute for MCMV M33, suggesting a conserved mechanism for immune cell trafficking and systemic spread.

Conclusions:

  • CMV systemic spread relies on the trafficking of infected dendritic cells through specific vascular routes (HEVs), regulated by viral GPCRs.
  • The functional conservation between MCMV M33 and HCMV US28 suggests HCMV may employ similar DC-mediated dissemination pathways.
  • Dendritic cell recirculation may chronically sustain and interconnect CMV reservoirs through continuous viral exchange.
Keywords:
CytomegalovirusG protein- coupled receptordendritic cellsmucosal infectionvirus spread

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