Constancy and Change in the 5'UTR of Yellow Fever Virus

The nucleotide composition of the 5UTR of the yellow fever virus (YFV) has been reported to be the most constant sequence in the viral genome, but a comprehensive analysis of this constancy has not been presented. The current report is an analysis of the 5UTRs from 48 sequences deposited in GenBank representing the seven described genotypes, five in Africa and two in the Americas. The YFV 5UTRs consist of 118-120 nucleotides, 92% (110/119) of which are constant in all sequences. The constancy is impressive and suggests that many participate in significant viral functions. Remarkably, analysis of the non-constant nucleotides revealed that in some instances the non-constant nucleotide changes persisted in one or a restricted number of related genotypes and were from sequences isolated over a considerable span of years. This constant feature of non-constant nucleotides is consistent with the concept that the changes were in response to different environmental features such as changes in mosquito hosts or animal reservoirs, particularly as a consequence of spread of YFV from Africa to the New World. Constancy of 5UTR in general may be helpful in distinction of viral species. Lastly, the presence of sequences of constant nucleotides greater than 19 nucleotides suggests regions of the 5UTR that may be exploited for use as non-codon RNA as treatment and diagnostic agents in a variety of viral diseases. ImportanceThe 5UTR is arguably the most neglected portion of the viral genome. It is frequently incomplete in the sequences deposited as otherwise complete sequences in GenBank. The current report is an analysis of complete 5UTR sequences selected from those deposited in GenBank and indicates that the 5UTR is 92% conserved confirming that it is a highly conserved portion of the viral genome and suggesting that each conserved nucleotide may be functionally significant. Repeated occurrences of even non-constant nucleotides belong to a restricted number of genotypes raising the possibility that adaptation to new mosquito hosts and animal reservoirs such as those that accompanied spread of yellow fever virus from Africa to the Western Hemisphere are relevant. Knowledge of prolonged strings of invariable nucleotides in the 5UTR has been used in designing a method for detecting YFV and may also be relevant for designing sequences for viral control of a variety of viruses.