Targeting virulence mechanisms for the prevention and therapy of arenaviral hemorrhagic fever

Lisa McLay, Aftab Ansari, Yuying Liang, Hinh Ly

Research output: Contribution to journalReview articlepeer-review

21 Scopus citations

Abstract

A number of arenaviruses are pathogenic for humans, but they differ significantly in virulence. Lassa virus, found in West Africa, causes severe hemorrhagic fever (HF), while the other principal Old World arenavirus, lymphocytic choriomeningitis virus, causes mild illness in persons with normal immune function, and poses a threat only to immunocompromised individuals. The New World agents, including Junin, Machupo and Sabia virus, are highly pathogenic for humans. Arenaviral HF is characterized by high viremia and general immune suppression, the mechanism of which is unknown. Studies using viral reverse genetics, cell-based assays, animal models and human genome-wide association analysis have revealed potential mechanisms by which arenaviruses cause severe disease in humans. Each of the four viral gene products (GPC, L polymerase, NP, and Z matrix protein) and several host-cell factors (e.g., α-dystroglycan) are responsible for mediating viral entry, genome replication, and the inhibition of apoptosis, translation and interferon-beta (IFNβ) production. This review summarizes current knowledge of the role of each viral protein and host factor in the pathogenesis of arenaviral HF. Insights from recent studies are being exploited for the development of novel therapies.

Original languageEnglish (US)
Pages (from-to)81-92
Number of pages12
JournalAntiviral Research
Volume97
Issue number2
DOIs
StatePublished - Feb 2013

Bibliographical note

Funding Information:
This work was supported by NIH Grants AI083409 to Y.L. and R01AI093580 and R56AI091805 to H.L. We apologize to colleagues whose work might not have been cited in this article due to space constraint.

Keywords

  • Antiviral therapy
  • Arenavirus
  • Lassa virus
  • Viral hemorrhagic fever
  • Virulence mechanisms

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