Dissecting the receptor-mediated infection mechanisms of hantaviruses

Research project

Description

Hantaviruses cause two disease syndromes in humans. New World agents, including Sin Nombre virus (SNV) and Andes virus (ANDV), cause a highly fatal hantavirus cardiopulmonary syndrome (HCPS) in the Americas, whereas Old World agents, including Hantaan virus (HTNV) and Puumala virus (PUUV), cause a less fatal hemorrhagic fever with renal syndrome (HFRS) in Eurasia. All known outbreaks have been traced to the zoonotic transmission of hantaviruses from their rodent host reservoirs, and human population growth and accelerating climate change may increase the frequency and size of hantavirus outbreaks in the coming decades. At present, no approved anti-hantavirus vaccines and therapeutics are available?their development is challenged by crucial gaps in our understanding of the virus-host molecular interactions that underpin infection, disease, and transmission. Current evidence indicates that human hantavirus disease arises from non-cytolytic viral infection and replication in capillary endothelial cells, and their attendant dysregulation. However, the molecular basis of endothelial cell infection, including the identities of essential receptor(s) for hantavirus entry, remains poorly understood. This proposal is centered on our recent discovery of protocadherin-1 (PCDH1), a member of the cadherin superfamily expressed in lung endothelial and epithelial cells, as a novel and critical candidate receptor for hantaviruses in endothelial cells. Our overall goals are to define the molecular mechanism by which PCDH1 mediates hantavirus entry and infection of endothelial cells; investigate the implications of this proposed virus?receptor interaction for hantavirus virulence and pathogenesis in vivo; determine its utility as a target for the development of antiviral therapeutics; and explore its potential role as a host barrier that influences hantavirus host range.
StatusActive
Effective start/end date7/1/176/30/22

Funding

  • National Institutes of Health: $766,950.00

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Hantavirus Infections
Hantavirus
Endothelial Cells
Disease Outbreaks
Viruses
Sin Nombre virus
Puumala virus
Hantaan virus
Hemorrhagic Fever with Renal Syndrome
Infectious Disease Transmission
Climate Change
Host Specificity
Population Growth
Zoonoses
Virus Diseases
Cadherins
Antiviral Agents
Virulence
Rodentia

Keywords

  • Medicine(all)
  • Immunology and Microbiology(all)