A possible association of fatal pneumonia with mutations of pandemic influenza A/H1N1 sw1 virus in the receptor-binding site of the HA1 subunit

[tetano]

Vopr Virusol. 2010 Jul-Aug;55(4):4-9.
[A possible association of fatal pneumonia with mutations of pandemic influenza A/H1N1 sw1 virus in the receptor-binding site of the HA1 subunit]

[Article in Russian]

[No authors listed]
Abstract

The paper gives the results of sequence analysis of 150 positive samples in real-time RT-PCR, including 47 autopsy materials from patients (including 10 pregnant women), who died from fatal pneumonia mainly in November-December 2009, in whom the lifetime etiological diagnosis had not been made and hence no early etiotropic therapy performed. 70% of the primary materials from the deceased patients were found to have pandemic influenza A(H1N1) v mutants in the lung tissue with D222G (15%), D222N (15%), D222E (2%) substitutions, as well as a mixture of mutants (38%). Nasopharyngeal lavages from 3 Chukotka deceased patients exhibited only consensus (nonmutant) D222 virus variants; there was a mixture of consensus and mutant virus variants in the trachea and a mixture of mutant ones in the lung. Preliminary data from the study of the interaction of the hemagglutinin of two strains having D222G and D222N mutations with 9 oligosaccharides imitating the variants of cell receptors for influenza A virus suggest that there is a double receptor specificity for alpha2'-3' and alpha2'-6'-sialosides with a preponderance of alpha2'-3'-specificity. Further spread of the mutants that have acquired a high virulence and preserved their capacity for the respiratory route of human infection may lead to the situation similar to that seen in the 1918-1919 pandemic. Another scenario for evolution of the virus is to preserve its receptor specificity for alpha2'-3'-sialosides and high virulence with losses of alpha2'-6' specificity and capacity for aerosol transmission, by damping the pandemic.

PMID: 20886705 [PubMed - in process]

http://www.ncbi.nlm.nih.gov/pubmed/20886705

 

[Anne]

Re: A possible association of fatal pneumonia with mutations of pandemic influenza A/H1N1 sw1 virus in the receptor-binding site of the HA1 subunit

[Detection of amino acid substitutions of asparaginic acid for glycine and asparagine at the receptor-binding site of hemagglutinin in the variants of pandemic influenza A/H1N1 virus from patients with fatal outcome and moderate form of the disease]

[Article in Russian]
L'vov DK, Iashkulov KB, Prilipov AG, Burtseva EI, Shchelkanov MIu, Shliapnikova OV, Poglazov AB, Sadykova GK, Dzhambinov SD, Fediakina IT, Bushkieva BTs, L'vov DN, Zhuravleva MM, Al'khovskiĭ SV, Samokhvalov EI, Trushakova SV, Lavrishcheva VV, Vereshchagin NN, Mikhaliaeva LB, Darbakova TA, Limanskaia OS, Dzhaparidze NI, Imkenova LN, Ledenev IuA, Boldyreva VV, Ivanov LI, Zdanovskaia NN.
Abstract

The paper analyzes the amino acid sequence of the receptor-binding site of hemagglutinin (HA) in the variants of pandemic influenza A/H1N1 swl from 18 patients with moderate (n=1) and fatal (n=17) forms of the disease in 2009. Nine samples contained asparaginic acid at position 222 of HA1 (D). This site exhibited mutations in 9 samples: D222G (n=3), D222N (n=3), and D222G/D222N (n=3). In one patient with the moderate form of the disease, D222G mutation was revealed after the second passage in the developing chick embryos; this mutation was not found in the primary sample from the patient. The findings suggest the mutant variants of the virus start to circulate among the population, which requires, firstly, continuation of molecular virological monitoring of the pandemic situation and, secondly, further study of the impact of amino acid substitutions at the receptor-binding site of HA1 on the increased virulence of influenza A virus.

PMID: 20608076 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/pubmed/20608076