4.5 Article

Pathogenicity and virulence mechanisms of Lassa virus and its animal modeling, diagnostic, prophylactic, and therapeutic developments

Journal

VIRULENCE
Volume 12, Issue 1, Pages 2989-3014

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/21505594.2021.2000290

Keywords

Lassa virus; arenavirus; mammarenavirus; pathogenicity; pathogenesis; virulence; vaccine; therapeutics; diagnostics; hemorrhagic fevers

Funding

  1. NIH [R56 AI091805, R01 AI093580, R01 AI131586]
  2. Minnesota Drive Global Food Ventures (MnDRIVE GFV) Graduate Professional Development Program
  3. Moe Graduate Fellowship

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Lassa fever is a deadly viral hemorrhagic disease endemic to West Africa, caused by Lassa virus. Currently, there are no approved therapeutics or vaccines against the virus, and its high genetic variability and immune evasion mechanisms pose challenges to developing effective treatments. Understanding the basic biology of LASV, its natural genetic variations, and immune evasion mechanisms is crucial for accurate diagnostics and effective therapeutics and vaccines.
Lassa fever (LF) is a deadly viral hemorrhagic disease that is endemic to West Africa. The causative agent of LF is Lassa virus (LASV), which causes approximately 300,000 infections and 5,000 deaths annually. There are currently no approved therapeutics or FDA-approved vaccines against LASV. The high genetic variability between LASV strains and immune evasion mediated by the virus complicate the development of effective therapeutics and vaccines. Here, we aim to provide a comprehensive review of the basic biology of LASV and its mechanisms of disease pathogenesis and virulence in various animal models, as well as an update on prospective vaccines, therapeutics, and diagnostics for LF. Until effective vaccines and/or therapeutics are available for use to prevent or treat LF, a better level of understanding of the basic biology of LASV, its natural genetic variations and immune evasion mechanisms as potential pathogenicity factors, and of the rodent reservoir-vector populations and their geographical distributions, is necessary for the development of accurate diagnostics and effective therapeutics and vaccines against this deadly human viral pathogen.

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