COMPARATIVE ANALYSIS OF SLIPPAGE-MEDIATED MUTATION BASED EVOLUTION IN THE NA(NI) GENE OF THE A/H5NI STRAIN OF VIETNAM AND GLOBAL ORIGINS

Abstract

The 5' part of the antigenic NA(N I ) gene of the A/H5N 1 virus has a specially high rate of mutation. Comparative analysis of 657 nucleotides ofNl (at 5' end) of the representative strains isolated in the period 1959 - 2006 revealed that there has been slippage-mediated mutation occurring in the nucleotide and amino acid of the N 1 gene, particularly, in the currently circulating strains (ie. those from 2003 to present). Tn the strains isolated during 2003 - 2006, there appeared a slippage-mediated mutation in N I gene, such as the deletion of60 nuc1eotides (20 amino acids). In our study, these include strains of China, Indonesia, Vietnam, Korea, Thailand, Malaysia, Nigeria, Laos. Up-to-date the A/H5Nl strains are divided into 3 evolutionary periods of mutation in the NI genes: 1959 - 1996; 1996 - 2003 and 2003- 2006. In the strains of 2003 - prescnt, there has been the shrink of the N 1 gene. The length of the N 1 is unchanged in the classical strains up to 1996; while the N 1 gene lost 57 nucleotides in those of 1996-2003 and 60 nucleotides in the circulating ones isolated after 2003, respectively. It is revealed that in those of H5N 1 after 2003 up to present, the essential mutation has occurred leading to the formation of the most specifically functioning NA(Nl) protein. It is speculated that the pathogenicity and the host adaptation become more and more multiple and diverse due to this change