Viruses Basel
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The 1918 H1N1 Spanish Influenza pandemic was the most severe pandemic in modern history. Unlike more recent pandemics, most of the 1918 H1N1 virus' genome was derived directly from an avian influenza virus. Recent avian-origin H5 A/goose/Guangdong/1/1996 (GsGd) and Asian H7N9 viruses have caused several hundred human infections with high mortality rates. ⋯ Several GsGd H5 and Asian H7N9 viruses display molecular changes that potentiate transmission and/or exhibit ability for limited transmission between ferrets. However, the hemagglutinin of these viruses is unstable; this likely represents the most significant obstacle to the emergence of a virus capable of efficient airborne transmission. Given the global disease burden of an influenza pandemic, continued surveillance and pandemic preparedness efforts against H5 GsGd and Asian lineage H7N9 viruses are warranted.
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Stockpiling neuraminidase inhibitors (NAIs) such as oseltamivir and zanamivir is part of a global effort to be prepared for an influenza pandemic. However, the contribution of NAIs for the treatment and prevention of influenza and its complications is largely debatable due to constraints in the ability to control for confounders and to explore unobserved areas of the drug effects. ⋯ The model recreated the oseltamivir effects and indicated that: (i) the efficacy was limited by design, (ii) a 99% efficacy could be achieved by using high drug doses (however, taking high doses of drug 48 h post-infection could only yield a maximum of 1.6-day reduction in the time to symptom alleviation), and (iii) contributions of oseltamivir to epidemic control could be high, but were observed only in fragile settings. In a typical influenza infection, NAIs' efficacy is inherently not high, and even if their efficacy is improved, the effect can be negligible in practice.
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Zika virus (ZIKV) causes no-to-mild symptoms or severe neurological disorders. To investigate the importance of viral and host genetic variations in determining ZIKV infection outcomes, we created three full-length infectious cDNA clones as bacterial artificial chromosomes for each of three spatiotemporally distinct and genetically divergent ZIKVs: MR-766 (Uganda, 1947), P6-740 (Malaysia, 1966), and PRVABC-59 (Puerto Rico, 2015). ⋯ More importantly, we identified one ZIKV-non-susceptible bovine cell line that has a block in viral entry but fully supports the subsequent post-entry steps. (iii) We showed that in mice, the three molecularly cloned ZIKVs differ in their neuropathogenicity, depending on the particular combination of viral and host genetic backgrounds, as well as in the presence or absence of type I/II interferon signaling. Overall, our findings demonstrate the impact of viral and host genetic variations on the replication kinetics and neuropathogenicity of ZIKV and provide multiple avenues for developing and testing medical countermeasures against ZIKV.