However, Taubenberger et al. To shed some light on these open questions, we studied a variety of influenza viruses with different origins by thorough phylogeny and codon usage. The genetic code is degenerated so that 64 triplets code for only 20 amino acids and a translation stop signal. During translation all 64 triplets are used, including starts and stops. Therefore, for most amino acids there is more than one triplet available, the maximum number being six synonymous codons.
Importantly, not all codons are used with equal frequencies. It seems possible to characterize a gene not only by the amino acid sequence that it codes for but also by its codon usage Taubenberger et al. Thus, codon usage may represent a genetic tool that can be used to clarify the phylogenetic relationship of related sequences Zhou et al. Therefore, studies of synonymous codon usage may reveal information about the molecular evolution of individual genes.
These codons were chosen because they are most abundant among the four synonymous codons of threonine. According to the results the viruses could be placed into groups, namely into human H1N1, H2N2, and H3N2, classical swine H1N1 isolates, and avian influenza viruses. These subsets called outliers of avian strains were designated clade 1 or clade 2, which are further defined below according to their phylogenetic relationship for details, see Fig. The numbers in the chamber shows estimated PB1 gene sequences.
The crosshatch represents human and new swine-origin SO H1N1 reassortants, which had acquired their PB1 gene from human H3N2 viruses for review, see Scholtissek ; Garten et al. Clade 1 and clade 2 viruses were isolated from birds, but they are outliers of bird viruses. They have a distinct RSCU pattern. The lines extending from the top and bottom of each box mark the minimum and maximum values within the data set that fall within an acceptable range. Any value outside of this range, called an outlier, is displayed as an individual point.
Phylogenetic tree of the PB1 genes of representative influenza viruses. Bootstrap values were estimated based on replicates and were given for all presented branches. A distance bar scale was shown under the tree. Clades CL are identified with different color backgrounds and with large letters as well as arrows, respectively. Overall, the most prominent differences were observed for the ACA codon.
Interestingly, the Brevig-Mission strain from x did not group with the avian strains group 2 in this analysis Fig. Instead, this isolate was found to be related to the human and swine H1N1 strains. The outliers observed in the patterns of human H1N1 viruses represent natural reassortants, which had acquired their PB1 gene from human H3N2 viruses. Interestingly, new swine origin SO H1N1 viruses, which were isolated from humans during the human swine flu outbreak of , also contain the avian-derived PB1 gene see Fig.
The outliers of swine H1N1 viruses see Fig. Six of these swine H1N1 viruses are triple reassortant swine viruses Accession numbers [Acc. The ENC value is calculated according to Novembre The only exception observed in the pattern of the human H3N2 viruses Fig.
The clear discrimination in the RSCU patterns of the PB1 gene was also apparent for the codons of glycine and lysine but not for the other amino acids data not shown , an observation that will be discussed below. As for the other viral genes that code for internal virus proteins, we did not observe apparent differences in the RSCU patterns for threonine, glycine, and lysine. Therefore we concentrated our studies mainly on the PB1 gene in all our further experiments.
In a more thorough study, mapping the 60 on average synonymous codons of threonine along the sequence of the PB1 protein, eight positions were identified at which threonine codons were identical for all strains examined, with minor exceptions. At these positions the codon usage was highly restricted, most likely due to structural constrains of the RNA.
Among the remaining 52 positions there were 32 positions where all four codons were equally used, suggesting that there is no bias for a special codon. Interestingly, there were 20 positions where the human and classical swine H1N1 viruses, including the Brevig-Mission isolate group 1 , collectively used a different codon compared to that found in group 2 viruses, comprising all the avian strains see Table 1 , above, with exceptions shown at the bottom of the table.
All fully sequenced PB1 genes of group 1 and group 2 viruses found in GenBank Supplemental Table 2 were analyzed and almost all sequences followed this rule Supplemental Table 1A. Similar patterns were observed with glycine Supplemental Table 1B , and all amino acids for which more than one codon exists data not shown.
As could be expected, these clear patterns as obtained with amino acids that are coded by four or six codons were not obtained by amino acids that are coded by only two codons. With the latter amino acids the pattern was somewhat less obvious there are not enough choices.
Interestingly, less clear patterns were observed in the other internal genes, as exemplified for glycine of the PB2 gene e. An exception was the HA gene. Here, the human and classical swine H1N1 viruses exhibited a distinct usage pattern of the threonine ACU codon, which was different from the avian H1 viruses Supplemental Fig.
Here again the Brevig-Mission strain was found with the group 1 viruses. Among the avian PB1 genes Fig. The data for five representative strains are included at the bottom of Table 1. We then estimated the absolute usage of synonymous codons of the PB1 gene by determining the effective number of codons ENC Fig.
The ENC value varies from 20 absolutely biased, only one codon is used for each amino acid to 61 no bias, all synonymous codons are used equally Wright, This analysis revealed that the PB1 gene of the pandemic virus had an ENC value similar to that of classical swine and human H1N1 viruses but not of avian viruses.
These values were significantly lower when compared to the ENC values of the classical swine strains and also of the human H1N1 strains. According to these ENC values of the PB1 gene, the pandemic virus of was most likely of swine and not of avian origin.
We extended our genetic analysis by constructing phylogenetic trees based on representative sequences from different viral origins, applying the neighbor-joining method Saitou and Nei ; Tamura et al. Both methods gave virtually the same results and consequently only neighbor-joining trees are presented in the paper.
The neighbor-joining algorithm Saitou and Nei ; Tamura et al. Figure 3 shows a distance-based phylogenetic tree of the PB1 gene in which the Brevig-Mission strain from clusters between the classical swine and human H1N1 viruses.
The same was found by Taubenberger et al. In the phylogenetic tree of PB1 , they form two separate clades that we designated clade 1 and 2. Clade 2 comprises viral isolates that do not belong to the H1N1 subtype, in contrast to isolates of clade 1. The avian clade 1 H1N1 viruses were isolated predominantly from domestic poultry. This clade also contains many recent H1N1 swine viruses Figs. The clade was adjacent to the H1N1 classical swine and human virus lineages.
Phylogenetic analysis of other influenza virus genes such as NP Fig. This indicated that clade 2 viruses were avian reassortants, which had obtained a group 1 PB1 gene from a group 1 virus. Phylogenetic tree of the NP genes of representative influenza viruses. Open in a separate window. A literature review. Ann Fr Anesth Reanim. Ann Acad Med Singapore. DOI : Pregnancy and pandemic influenza A H1N1 Current concepts for anaesthesia and critical care medicine.
Lapinsky SE. Public Health Rep. Fatal swine influenzapneumonia during late pregnancy. Arch Intern Med. Severe respiratory disease concurrent with the circulation of H1N1 influenza. New Eng J Med. J Immunol. Increased susceptibility for superinfection with Streptococcus pneumoniae during influenza virus infection is not caused by TLR7-mediated lymphopenia. PloS One. Crit Care Med. Rodrigues J, Niederman MS. Pneumonia complicating pregnancy.
Blog de Pierrot. Or le Dr Angelique Coetzee n'est pas n'importe qui. On annonce une intervention officielle du gouvernement mardi en Afrique du Sud. Source Le Figaro. La grippe espagnole, entre 50 et millions de morts Depuis, tous les virus de la grippe que nous connaissons sont des variants lointains de ce virus ancestral. Pierrot Dupuy. Pierrot Dupuy est le fondateur de Zinfos En savoir plus sur cet auteur.
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