Influenza viruses with B/Yamagata- and B/Victoria-like neuraminidases are differentially affected by mutations that alter antiviral susceptibility.
نویسندگان
چکیده
OBJECTIVES The burden of disease due to influenza B is often underestimated. Clinical studies have shown that oseltamivir, a widely used neuraminidase inhibitor (NAI) antiviral drug, may have reduced effectiveness against influenza B viruses. Therefore, it is important to study the effect of neuraminidase mutations in influenza B viruses that may further reduce NAI susceptibility, and to determine whether these mutations have the same effect in the two lineages of influenza B viruses that are currently circulating (B/Yamagata-like and B/Victoria-like). METHODS We characterized the effect of 16 amino acid substitutions across five framework residues and four monomeric interface residues on the susceptibility to four different NAIs (oseltamivir, zanamivir, peramivir and laninamivir). RESULTS Framework residue mutations E117A and E117G conferred highly reduced inhibition to three of the four NAIs, but substantially reduced neuraminidase activity, whereas other framework mutations retained a greater level of NA activity. Mutations E105K, P139S and G140R of the monomeric interface were also found to cause highly reduced inhibition, but, interestingly, their effect was substantially greater in a B/Victoria-like neuraminidase than in a B/Yamagata-like neuraminidase, with some susceptibility values being up to 1000-fold different between lineages. CONCLUSIONS The frequency and the effect of key neuraminidase mutations on neuraminidase activity and NAI susceptibility can differ substantially between the two influenza B lineages. Therefore, future surveillance, analysis and interpretation of influenza B virus NAI susceptibility should consider the B lineage of the neuraminidase in the same manner as already occurs for different influenza A neuraminidase subtypes.
منابع مشابه
Outcomes and Susceptibility to Neuraminidase Inhibitors in Individuals Infected With Different Influenza B Lineages: The Influenza Resistance Information Study.
BACKGROUND Little is known about how influenza infections caused by B/Victoria and B/Yamagata virus lineages compare with respect to disease course and susceptibility to antiviral therapy. METHODS Data from patients with influenza B infections from the first 5 years (2009-2013) of the prospective Influenza Resistance Information Study (IRIS, NCT00884117) were evaluated. Cultured viruses were ...
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ورودعنوان ژورنال:
- The Journal of antimicrobial chemotherapy
دوره 70 7 شماره
صفحات -
تاریخ انتشار 2015