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  • Review Article
  • Published:

Uncovering the mysteries of hantavirus infections

Nature Reviews Microbiology volume 11, pages 539–550 (2013)Cite this article

Subjects

Key Points

  • Hantaviruses are negative-sense single-stranded RNA viruses that infect many species of rodents, shrews, moles and bats.

  • Hantaviruses primarily replicate in the endothelium and might use integrins to enter cells. Following entry, the virus synthesizes viral mRNA to produce viral proteins and replicate the genome (comprising small, medium and large segments), although the exact details of these processes remain unclear. The viral genome is encapsided by nucleocapsid protein to form ribonucleoproteins, which interact with viral glycoprotein to form virus particles.

  • The three segments of viral RNA encode nucleocapsid protein, glycoprotein and RNA-dependent RNA polymerase.

  • Infection of reservoir hosts is asymptomatic, possibly owing to immunosuppression.

  • Infection of humans causes either haemorrhagic fever with renal syndrome or hantavirus cardiopulmonary syndrome.

  • Disease pathology is characterized by increased permeability of the endothelial cells lining capillaries and is also thought to be mediated by enhanced immune responses, such as increased production of cytokines and expansion of cytotoxic T cells.

Abstract

Hantaviruses are negative-sense single-stranded RNA viruses that infect many species of rodents, shrews, moles and bats. Infection in these reservoir hosts is almost asymptomatic, but some rodent-borne hantaviruses also infect humans, causing either haemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS). In this Review, we discuss the basic molecular properties and cell biology of hantaviruses and offer an overview of virus-induced pathology, in particular vascular leakage and immunopathology.

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Figure 1: Hantavirus particles, genes and proteins.
Figure 2: The life cycle and replication of hantaviruses.
Figure 3: Viral genome replication and transcription.
Figure 4: Vasculopathy in hantavirus-mediated diseases.

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Acknowledgements

The authors' research was supported by European Commission Project QLK2-CT-2002-01358 (grant GOCE-CT-2003-010284 EDEN); the European Union (grant FP7-261504 EDENext; the project is catalogued as EDENext140 by the EDENext Steering Committee); The Academy of Finland; the Sigrid Jusélius Foundation; the Magnus Ehrnrooth Foundation; the Helsinki University Central Hospital, Finland; and Tampere University Hospital, Finland. The authors thank J. Antonen, P. Arstila, S. Butcher, F. Ennis, T. Hautala, J. Huiskonen, M. Hurme, J. Klingström, H. Lankinen, D. Libraty, Å. Lundkvist, A. Pasternack, A. Plyusnin, O. Vapalahti (as well as their former and current students and technicians) and the authors' former and current students and technicians for collaboration on research concerning hantavirus infections.

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Authors and Affiliations

  1. Department of Virology, Haartman Institute, P.O. Box 21

    Antti Vaheri, Tomas Strandin, Jussi Hepojoki & Tarja Sironen

  2. University of Helsinki, Helsinki, FI-00014, Finland

    Antti Vaheri, Tomas Strandin, Jussi Hepojoki & Tarja Sironen

  3. Finnish Forest Research Institute, Vantaa, FI-01301, Finland

    Heikki Henttonen

  4. School of Medicine, University of Tampere, Tampere, FI-33521, Finland

    Satu Mäkelä & Jukka Mustonen

  5. Department of Internal Medicine, Tampere University Hospital, Tampere, FI-33521, Finland

    Satu Mäkelä & Jukka Mustonen

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  1. Antti Vaheri
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Correspondence to Antti Vaheri.

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Glossary

Thrombocytopenia

A low platelet count in the blood.

Cytotoxic CD8+ T cells

A subpopulation of T cells that kills abnormal (infected, cancerous or damaged) cells as part of the adaptive immune system.

Complement system

Serum proteins that can protect against infection as part of innate immunity. This efficiently regulated system has three major pathways, namely the classical, alternative and the lectin-dependent pathways.

Clathrin-dependent endocytosis

A pathway for the internalization of plasma membrane proteins. Receptors cluster in membrane domains containing a polymeric clathrin coat and a complex of adaptor proteins and GTPases, leading to membrane invagination and scission to form a clathrin-coated vesicle containing the internalized receptors.

Early endosomes

Intracellular vesicular structures that are precursors of mature endosomes and have an important role in endocytosis.

P bodies

Cytoplasmic foci that are thought to store and degrade translationally repressed RNA.

Regulatory T cells

A subpopulation of T cells that modulates the immune system. These are CD4+CD25+FOX3P+ cells that have suppressor activity towards other T cells either by cell–cell contact or by cytokine release.

Pattern recognition receptors

A highly diverse group of soluble and surface-bound proteins that can detect specific molecular surface structures.

Proteinuria

The presence of excess protein in the urine.

Leukocytosis

A condition in which the number of white blood cells is above the normal range. Frequently associated with inflammation.

Fibrinolysis

A process whereby fibrin clots (the products of blood coagulation) are broken down.

Acute-phase proteins

A group of proteins, including C-reactive protein and fibrinogen, the blood concentration of which changes in response to trauma, inflammation or disease. These proteins can be inhibitors or mediators of inflammation.

Caspases

A family of cysteine proteases that execute cell death events in the apoptotic pathway.

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Vaheri, A., Strandin, T., Hepojoki, J. et al. Uncovering the mysteries of hantavirus infections. Nat Rev Microbiol 11, 539–550 (2013). https://doi.org/10.1038/nrmicro3066

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