TY - JOUR

T1 - Evaluation of HA-D222G/N polymorphism using targeted NGS analysis in A(H1N1)pdm09 influenza virus in Russia in 2018–2019

AU - Danilenko, Alexey V.

AU - Kolosova, Natalia P.

AU - Shvalov, Alexander N.

AU - Ilyicheva, Tatyana N.

AU - Svyatchenko, Svetlana V.

AU - Durymanov, Alexander G.

AU - Bulanovich, Julia A.

AU - Goncharova, Natalia I.

AU - Susloparov, Ivan M.

AU - Marchenko, Vasiliy Y.

AU - Tregubchak, Tatyana V.

AU - Gavrilova, Elena V.

AU - Maksyutov, Rinat A.

AU - Ryzhikov, Alexander B.

N1 - Funding Information: This work was supported by State Assignments no. 1/16, 2/18 and 2/21 (FBRI SRC VB ?Vector?, Rospotrebnadzor), http://www.vector. nsc.ru/ The funders supported obtaining a number of reagents, funded sequencing, data analysis and covered publication fees. Publisher Copyright: © 2021 Danilenko et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/4

Y1 - 2021/4

N2 - Outbreaks of influenza, which is a contagious respiratory disease, occur throughout the world annually, affecting millions of people with many fatal cases. The D222G/N mutations in the hemagglutinin (HA) gene of A(H1N1)pdm09 are associated with severe and fatal human influenza cases. These mutations lead to increased virus replication in the lower respiratory tract (LRT) and may result in life-threatening pneumonia. Targeted NGS analysis revealed the presence of mutations in major and minor variants in 57% of fatal cases, with the proportion of viral variants with mutations varying from 1% to 98% in each individual sample in the epidemic season 2018–2019 in Russia. Co-occurrence of the mutations D222G and D222N was detected in a substantial number of the studied fatal cases (41%). The D222G/N mutations were detected at a low frequency (less than 1%) in the rest of the studied samples from fatal and nonfatal cases of influenza. The presence of HA D222Y/V/A mutations was detected in a few fatal cases. The high rate of occurrence of HA D222G/N mutations in A(H1N1)pdm09 viruses, their increased ability to replicate in the LRT and their association with fatal outcomes points to the importance of monitoring the mutations in circulating A(H1N1)pdm09 viruses for the evaluation of their epidemiological significance and for the consideration of disease prevention and treatment options.

AB - Outbreaks of influenza, which is a contagious respiratory disease, occur throughout the world annually, affecting millions of people with many fatal cases. The D222G/N mutations in the hemagglutinin (HA) gene of A(H1N1)pdm09 are associated with severe and fatal human influenza cases. These mutations lead to increased virus replication in the lower respiratory tract (LRT) and may result in life-threatening pneumonia. Targeted NGS analysis revealed the presence of mutations in major and minor variants in 57% of fatal cases, with the proportion of viral variants with mutations varying from 1% to 98% in each individual sample in the epidemic season 2018–2019 in Russia. Co-occurrence of the mutations D222G and D222N was detected in a substantial number of the studied fatal cases (41%). The D222G/N mutations were detected at a low frequency (less than 1%) in the rest of the studied samples from fatal and nonfatal cases of influenza. The presence of HA D222Y/V/A mutations was detected in a few fatal cases. The high rate of occurrence of HA D222G/N mutations in A(H1N1)pdm09 viruses, their increased ability to replicate in the LRT and their association with fatal outcomes points to the importance of monitoring the mutations in circulating A(H1N1)pdm09 viruses for the evaluation of their epidemiological significance and for the consideration of disease prevention and treatment options.

UR - http://www.scopus.com/inward/record.url?scp=85104945642&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0251019

DO - 10.1371/journal.pone.0251019

M3 - Review article

C2 - 33914831

AN - SCOPUS:85104945642

VL - 16

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 4 April

M1 - e0251019

ER -