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

Abstract

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.

Understanding Immune Responses to Lassa Virus Infection and to Its Candidate Vaccines

“…Due to the relatively high genetic variation among different LASV lineages and the fact that LF patients show symptoms similar to those of other febrile illnessses, diagnosing LASV can be particularly challenging. There are some LASV diagnostics available (for a review, see Murphy & Ly, 2021 [ 148 ]), but clinical settings rarely use laboratory-developed protocols, particularly in areas with limited resources (where LASV is endemic). There is an urgent need to advance current diagnostics for clinical validation and to obtain regulatory permits necessary for clinical application.…”

“…Despite the high estimation of potential LASV infections in humans, no effective therapeutics or vaccines are currently available against this deadly virus. Supportive care and ribavirin are the only treatments that have been authorized for use to treat LF (for a review, see Murphy & Ly, 2021 [ 148 ]), although the effectiveness of ribavirin varies with the severity of LF and the timing of its clinical application.…”

Erkrankungen durch hochpathogene Erreger – Teil 1

“…Eine weitere potenzielle Übertragungsmöglichkeit liegt im Verzehr von Fleisch geschlachteter infizierter Nager (Bush Meat) als relevante Nahrungsquelle in vielen westafrikanischen Ländern [27].…”

Hearing loss in outbred Hartley guinea pigs experimentally infected with Pichinde virus as a surrogate model of human mammarenaviral hemorrhagic fevers

“…LF is included in the World Health Organization (WHO)’s list of diseases with the highest urgency for infectious disease research [ 5 ]. LF was designated as one of the WHO blueprint priority diseases because of its relatively high case load, the lack of available vaccines, and highly efficacious anti-viral treatments [ 6 ] and its pandemic potential. LASV has caused multiple disease outbreaks in several countries in western Africa and has been imported into other countries, such as the US, the EU, and Japan through means of international travel [ 7 ].…”