Hantavirus entry: Perspectives and recent advances

Eva Mittler, Maria Eugenia Dieterle, Lara M. Kleinfelter, Megan M. Slough, Kartik Chandran, Rohit K. Jangra

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations

Abstract

Hantaviruses are important zoonotic pathogens of public health importance that are found on all continents except Antarctica and are associated with hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. Despite the significant disease burden they cause, no FDA-approved specific therapeutics or vaccines exist against these lethal viruses. The lack of available interventions is largely due to an incomplete understanding of hantavirus pathogenesis and molecular mechanisms of virus replication, including cellular entry. Hantavirus Gn/Gc glycoproteins are the only viral proteins exposed on the surface of virions and are necessary and sufficient to orchestrate virus attachment and entry. In vitro studies have implicated integrins (β1–3), DAF/CD55, and gC1qR as candidate receptors that mediate viral attachment for both Old World and New World hantaviruses. Recently, protocadherin-1 (PCDH1) was demonstrated as a requirement for cellular attachment and entry of New World hantaviruses in vitro and lethal HPS in vivo, making it the first clade-specific host factor to be identified. Attachment of hantavirus particles to cellular receptors induces their internalization by clathrin-mediated, dynamin-independent, or macropinocytosis-like mechanisms, followed by particle trafficking to an endosomal compartment where the fusion of viral and endosomal membranes can occur. Following membrane fusion, which requires cholesterol and acid pH, viral nucleocapsids escape into the cytoplasm and launch genome replication. In this review, we discuss the current mechanistic understanding of hantavirus entry, highlight gaps in our existing knowledge, and suggest areas for future inquiry.

Original languageEnglish (US)
Title of host publicationAdvances in Virus Research
EditorsMargaret Kielian, Thomas C. Mettenleiter, Marilyn J. Roossinck
PublisherAcademic Press Inc.
Pages185-224
Number of pages40
ISBN (Print)9780128183946
DOIs
StatePublished - 2019

Publication series

NameAdvances in Virus Research
Volume104
ISSN (Print)0065-3527
ISSN (Electronic)1557-8399

Keywords

  • Bunyavirus
  • Hantavirus
  • Hantavirus pulmonary syndrome
  • Hemorrhagic fever with renal syndrome
  • Vaccines
  • Viral entry
  • Viral glycoprotein structure
  • Viral glycoproteins
  • Viral receptors

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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    Mittler, E., Dieterle, M. E., Kleinfelter, L. M., Slough, M. M., Chandran, K., & Jangra, R. K. (2019). Hantavirus entry: Perspectives and recent advances. In M. Kielian, T. C. Mettenleiter, & M. J. Roossinck (Eds.), Advances in Virus Research (pp. 185-224). (Advances in Virus Research; Vol. 104). Academic Press Inc.. https://doi.org/10.1016/bs.aivir.2019.07.002