Influenza viruses with B/Yamagata- and B/Victoria-like neuraminidases are differentially affected by mutations that alter antiviral susceptibility.

نویسندگان

  • Rubaiyea Farrukee
  • Sook-Kwan Leang
  • Jeff Butler
  • Raphael T C Lee
  • Sebastian Maurer-Stroh
  • Danielle Tilmanis
  • Sheena Sullivan
  • Jennifer Mosse
  • Ian G Barr
  • Aeron C Hurt
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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

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 ...

متن کامل

Influenza B Viruses in the Population of Province of Vojvodina during the 2012/2013 Season: Differentiation of B/Yamagata and B/Victoria Lineages by Real-time RT-PCR, Antigenic and Phylogenetic Characterization.

INTRODUCTION At present, two phylogenetically distinct influenza B virus lineages, B/Yamagata and B/ Victoria, co-circulate worldwide and can cause significant morbidity and mortality. OBJECTIVE The aim of this study was to determine the prevalences of two influenza B virus lineages in the population of Vojvodina and to identify their antigenic and phylogenetic properties. METHODS A total o...

متن کامل

Differential age susceptibility to influenza B/Victoria lineage viruses in the 2015 Australian influenza season.

Influenza B viruses make up an important part of the burden from seasonal influenza globally. The 2015 season in Australia saw an unusual predominance of influenza B with a distinctive switch during the season from B/Yamagata/16/88 lineage viruses to B/Victoria/2/87 lineage viruses. We also noted significant differences in the age groups infected by the different B lineages, with B/Victoria inf...

متن کامل

Forty five percent of the Israeli population were infected with the influenza B Victoria virus during the winter season 2015–16

While infection with influenza A viruses has been extensively investigated, infections with influenza B viruses which are commonly categorized into the highly homologous Victoria and Yamagata lineages, are less studied, despite their considerable virulence. Here we used RT-PCR assays, hemagglutination inhibition assays and antibody titers to determine the levels of influenza B infection. We rep...

متن کامل

Epidemiology of influenza B/Yamagata and B/Victoria lineages in South Africa, 2005-2014

BACKGROUND Studies describing the epidemiology of influenza B lineages in South Africa are lacking. METHODS We conducted a prospective study to describe the circulation of influenza B/Victoria and B/Yamagata lineages among patients of all ages enrolled in South Africa through three respiratory illness surveillance systems between 2005 and 2014: (i) the Viral Watch (VW) program enrolled outpat...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • The Journal of antimicrobial chemotherapy

دوره 70 7  شماره 

صفحات  -

تاریخ انتشار 2015