Publications by authors named "J L WESTOVER"
Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a recently emerged tickborne virus in east Asia with over 18,000 confirmed cases. With a high case fatality ratio, SFTSV has been designated a high priority pathogen by the WHO and the NIAID. Despite this, there are currently no approved therapies or vaccines to treat or prevent SFTS.
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- Development of broad-spectrum antiviral therapies, like 4'-fluorouridine (4'-FlU), is crucial for effectively responding to outbreaks and pandemics caused by emerging viruses, particularly those that cause hemorrhagic fevers, which have seen increasing morbidity and mortality rates.
- 4'-FlU has shown antiviral activity against several hemorrhagic fever viruses in cell cultures and has demonstrated high efficacy in guinea pig models infected with lethal arenaviruses, maintaining its effectiveness at low doses.
- When administered late in infection, 4'-FlU not only resolved clinical symptoms quickly but also showcased its potential as a therapeutic option with a broader application against various viral pathogens.
Article Synopsis
- - Argentine hemorrhagic fever, caused by the Junín virus (JUNV), has a high mortality rate and currently relies on limited treatments like immune plasma, highlighting the need for new antiviral therapies.
- - The fusion inhibitor LHF-535 and nucleoside analog favipiravir have shown potential in combating arenaviral infections, but using favipiravir alone requires high doses for effectiveness against JUNV.
- - Combining LHF-535 with a lower dose of favipiravir in guinea pig models resulted in complete protection from JUNV, demonstrating the potential of this drug combination to broaden treatment options and prevent drug resistance.
Unlabelled: Heartland virus (HRTV) is an emerging tick-borne bandavirus that causes a febrile illness of varying severity in humans, with cases reported in eastern and midwestern regions of the United States. No vaccines or approved therapies are available to prevent or treat HRTV disease. Here, we describe the genetic changes, natural history of disease, and pathogenesis of a mouse-adapted HRTV (MA-HRTV) that is uniformly lethal in 7- to 8-week-old AG129 mice at low challenge doses.
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- Live-attenuated virus vaccines like Candid#1 aim to protect against diseases (e.g., Argentine hemorrhagic fever) but have risks of reverting to a more pathogenic form due to genetic mutations.
- In studies with mutant strains (I427F and A168T+I427F rCan), researchers found that while some mutations increased virulence in mice, others showed only modest effects, indicating a complex relationship between genetic changes and vaccine safety.
- To ensure the safety of future Candid#1 vaccines, it's crucial to stabilize key genetic mutations to prevent reversion to virulent strains.