CpG Suppression Is An Important Factor That Shapes The Codon Usage Bias Of Avian Influenza Virus

Influenza A virus belongs to the Orthomyxoviridae,which is one of the most pathogenic viruses to humans. It have caused three pandemics during the 20th century.Human have researched the Influenza viruses for quite a long time, however because of the high mutation rate and special reassorment phenomenon of the segments among different subtypes of influenza virus, there still a long way to find the proper strategy to against influenza virus. Vaccines need to be reformulated annually by updating the seed strains. However, when the antigenicities of the seed strains and wild viruses do not match, vaccines fail to protect the vaccines.Avian influenza virus (AIV) is the H5N1 subtype of the influenza A virus. Since the species specificity of influenza viruses, it thought that there is a huge gap for influenza viruses transmit among hosts. The first case of human infected AIV was reported in HongKong 1997.People are paying more attention to the AIV, since the high fatality rate and the latent capability to transmission among humans. According to the report of WHO April the 2nd 2008, 107 Indonesians died from the AIV. Although no human to human AIV transmission have been reported, the high mutation rate and the special segments reassorment among subtypes of influenza viruses leading people to worry about another epidemic will be caused by AIV.Keeping the essential functions and escaping the host immune system recognition, AIV genomes are suffering the positive and purify selection at the mean time. The codon usage bias can reveal the changes of the AIV genome under these two selections. Pilot researches have studied the codon usage bias by relative synonymous codon usage (RSCU) and effective number of codons, however analysis the codons using some special dinucleotides have been missing in these researches. Some special CG motifs in genome of bacterial and DNA virus have been proved to stimulate the immune system of hosts and play an important role in the evolution of these species. Little is known about the similar mechanism's impact to the AIV genome.We detailed analyzed the dinucleotides and synonymous codon usage of the AIV genome in the NCBI influenza virus database. After analyzed the 8 segments and 11 genes of the AIV, we have found that:1. The practical CG dinucleotides usages in the 8 segments of AIV are significant less than the theoretical usage by the chi-test2. Most of the codons using CG dinucleotides'RSCUs are less than 1 in the 11 genes of AIV. Those RSCU of CG codons greater than 1 are all in the overlapping genes. These first two results show CG dinucleotides are significant suppressed in the genome of AIV.3. The practical usages of CA and UG dinucleotides are greater than the theoretical usage. This result shows that the CA and UG dinucleotides share the CpG suppression pressure equally.Our results show that CpG suppression is an important factor that shapes the synonymous codon usage of AIV genome.