scholarly journals Virulence-Associated Substitution D222G in the Hemagglutinin of 2009 Pandemic Influenza A(H1N1) Virus Affects Receptor Binding

2010 ◽  
Vol 84 (22) ◽  
pp. 11802-11813 ◽  
Author(s):  
Salin Chutinimitkul ◽  
Sander Herfst ◽  
John Steel ◽  
Anice C. Lowen ◽  
Jianqiang Ye ◽  
...  

ABSTRACT The clinical impact of the 2009 pandemic influenza A(H1N1) virus (pdmH1N1) has been relatively low. However, amino acid substitution D222G in the hemagglutinin of pdmH1N1 has been associated with cases of severe disease and fatalities. D222G was introduced in a prototype pdmH1N1 by reverse genetics, and the effect on virus receptor binding, replication, antigenic properties, and pathogenesis and transmission in animal models was investigated. pdmH1N1 with D222G caused ocular disease in mice without further indications of enhanced virulence in mice and ferrets. pdmH1N1 with D222G retained transmissibility via aerosols or respiratory droplets in ferrets and guinea pigs. The virus displayed changes in attachment to human respiratory tissues in vitro, in particular increased binding to macrophages and type II pneumocytes in the alveoli and to tracheal and bronchial submucosal glands. Virus attachment studies further indicated that pdmH1N1 with D222G acquired dual receptor specificity for complex α2,3- and α2,6-linked sialic acids. Molecular dynamics modeling of the hemagglutinin structure provided an explanation for the retention of α2,6 binding. Altered receptor specificity of the virus with D222G thus affected interaction with cells of the human lower respiratory tract, possibly explaining the observed association with enhanced disease in humans.

2010 ◽  
Vol 15 (8) ◽  
pp. 1151-1159 ◽  
Author(s):  
Larisa V Gubareva ◽  
A Angelica Trujillo ◽  
Margaret Okomo-Adhiambo ◽  
Vasiliy P Mishin ◽  
Varough M Deyde ◽  
...  

ACS Omega ◽  
2019 ◽  
Vol 4 (11) ◽  
pp. 14560-14568 ◽  
Author(s):  
Jaewoo Lim ◽  
Jihyun Byun ◽  
Kyeonghye Guk ◽  
Seul Gee Hwang ◽  
Pan Kee Bae ◽  
...  

2010 ◽  
Vol 15 (9) ◽  
Author(s):  
A Kilander ◽  
R Rykkvin ◽  
S G Dudman ◽  
O Hungnes

Infection with the recently emerged pandemic influenza A(H1N1) virus causes mild disease in the vast majority of cases, but sporadically also very severe disease. A specific mutation in the viral haemagglutinin (D222G) was found with considerable frequency in fatal and severe cases in Norway, but was virtually absent among clinically mild cases. This difference was statistically significant and our data are consistent with a possible causal relationship between this mutation and the clinical outcome.


2013 ◽  
Vol 159 (6) ◽  
pp. 1279-1291 ◽  
Author(s):  
E. Bart Tarbet ◽  
Almut H. Vollmer ◽  
Brett L. Hurst ◽  
Dale L. Barnard ◽  
Yousuke Furuta ◽  
...  

2010 ◽  
Vol 16 (S2) ◽  
pp. 1122-1123
Author(s):  
CS Goldsmith ◽  
MG Metcalfe ◽  
W-J Shieh ◽  
DM Blau ◽  
DC Rollin ◽  
...  

Extended abstract of a paper presented at Microscopy and Microanalysis 2010 in Portland, Oregon, USA, August 1 – August 5, 2010.


2013 ◽  
Vol 19 (3) ◽  
Author(s):  
Rebekah H. Borse ◽  
Sundar S. Shrestha ◽  
Anthony E. Fiore ◽  
Charisma Y. Atkins ◽  
James A. Singleton ◽  
...  

2010 ◽  
Vol 52 (Supplement 1) ◽  
pp. S94-S101 ◽  
Author(s):  
K. B. Janusz ◽  
J. E. Cortes ◽  
F. Serdarevic ◽  
R. C. Jones ◽  
J. D. Jones ◽  
...  

2010 ◽  
Vol 15 (31) ◽  
Author(s):  
K Waalen ◽  
A Kilander ◽  
S G Dudman ◽  
G H Krogh ◽  
T Aune ◽  
...  

The prevalence of antibodies reactive to the 2009 pandemic influenza A(H1N1) was determined in sera collected before the start of the pandemic, during the early phase, and after the main epidemic wave and nationwide vaccination campaign in Norway. A substantial rise in prevalence of antibodies at protective titres, from 3.2% to 44.9%, was observed between August 2009 and January 2010. The highest prevalence, 65.3%, was seen in the age group of 10-19 year-olds.


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