Contribution of neuraminidase of influenza viruses to the sensitivity to sera inhibitors and reassortment efficiency. / Kiseleva, Irina; Larionova, Natalie; Fedorova, Ekaterina; Bazhenova, Ekaterina; Dubrovina, Irina; Isakova-Sivak, Irina; Rudenko, Larisa.
In: Open Microbiology Journal, Vol. 8, No. 1, 2014, p. 59-70.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Contribution of neuraminidase of influenza viruses to the sensitivity to sera inhibitors and reassortment efficiency
AU - Kiseleva, Irina
AU - Larionova, Natalie
AU - Fedorova, Ekaterina
AU - Bazhenova, Ekaterina
AU - Dubrovina, Irina
AU - Isakova-Sivak, Irina
AU - Rudenko, Larisa
PY - 2014
Y1 - 2014
N2 - Live attenuated influenza vaccine (LAIV) represent reassortant viruses with hemagglutinin (HA) and neuraminidase (NA) gene segments inherited from circulating wild-type (WT) parental influenza viruses recommended for inclusion into seasonal vaccine formulation, and the 6 internal protein-encoding gene segments from cold-adapted attenuated master donor viruses (genome composition 6:2). In this study, we describe the obstacles in developing LAIV strains while taking into account the phenotypic peculiarities of WT viruses used for reassortment. Genomic composition analysis of 849 seasonal LAIV reassortants revealed that over 80% of reassortants based on inhibitor-resistant WT viruses inherited WT NA, compared to 26% of LAIV reassortants based on inhibitor-sensitive WT viruses. In addition, the highest percentage of LAIV genotype reassortants was achieved when WT parental viruses were resistant to non-specific serum inhibitors. We demonstrate that NA may play a role in influenza virus sensitivity to non -specific serum inhibitors. Replacing NA of inhibitor-sensitive WT virus with the NA of inhibitor-resistant master donor virus significantly decreased the sensitivity of the resulting reassortant virus to serum heat-stable inhibitors.
AB - Live attenuated influenza vaccine (LAIV) represent reassortant viruses with hemagglutinin (HA) and neuraminidase (NA) gene segments inherited from circulating wild-type (WT) parental influenza viruses recommended for inclusion into seasonal vaccine formulation, and the 6 internal protein-encoding gene segments from cold-adapted attenuated master donor viruses (genome composition 6:2). In this study, we describe the obstacles in developing LAIV strains while taking into account the phenotypic peculiarities of WT viruses used for reassortment. Genomic composition analysis of 849 seasonal LAIV reassortants revealed that over 80% of reassortants based on inhibitor-resistant WT viruses inherited WT NA, compared to 26% of LAIV reassortants based on inhibitor-sensitive WT viruses. In addition, the highest percentage of LAIV genotype reassortants was achieved when WT parental viruses were resistant to non-specific serum inhibitors. We demonstrate that NA may play a role in influenza virus sensitivity to non -specific serum inhibitors. Replacing NA of inhibitor-sensitive WT virus with the NA of inhibitor-resistant master donor virus significantly decreased the sensitivity of the resulting reassortant virus to serum heat-stable inhibitors.
KW - Influenza virus
KW - Live influenza vaccine
KW - Neuraminidase
KW - Normal serum inhibitors
KW - Reassortment
UR - http://www.scopus.com/inward/record.url?scp=84928954212&partnerID=8YFLogxK
U2 - 10.2174/1874285801408010059
DO - 10.2174/1874285801408010059
M3 - Article
AN - SCOPUS:84928954212
VL - 8
SP - 59
EP - 70
JO - Open Microbiology Journal
JF - Open Microbiology Journal
SN - 1874-2858
IS - 1
ER -
ID: 99523665