Abstract
Usutu virus (USUV) is a mosquito-borne flavivirus, belonging to the Japanese encephalitis antigenic complex, that circulates among mosquitoes and birds. We describe and analyze the complete genome sequence of the first USUV strain isolated from an immunocompromised patient with neuroinvasive disease. This USUV isolate showed an overall nucleotide identity of 99% and 96%, respectively, with the genomes of isolates from Europe and Africa. Comparison of the human USUV complete polyprotein sequence with bird-derived strains, showed two unique amino acid substitutions. In particular, one substitution (S595G) was situated in the DIII domain of the viral Envelope protein that is recognized by flavivirus neutralizing antibodies. An additional amino acid substitution (D3425E) was identified in the RNA-dependent RNA polymerase (RdRp) domain of the NS5 protein. This substitution is remarkable since E3425 is highly conserved among the other USUV isolates that were not associated with human infection. However, a similar substitution was observed in Japanese encephalitis and in West Nile viruses isolated from humans. Phylogenetic analysis of the human USUV strain revealed a close relationship with an Italian strain isolated in 2009. Analysis of synonymous nucleotide substitutions (SNSs) among the different USUV genomes showed a specific evolutionary divergence among different countries. In addition, 15 SNSs were identified as unique in the human isolate. We also identified four specific nucleotide substitutions in the 5′ and 3′ untranslated regions (UTRs) in the human isolate that were not present in the other USUV sequences. Our analyses provide the basis for further experimental studies aimed at defining the effective role of these mutations in the USUV genome, their potential role in the development of viral variants pathogenic for humans and their evolution and dispersal out of Africa.
Highlights
Usutu virus (USUV), an arthropod-borne flavivirus within the Japanese encephalitis virus antigenic complex, is closely related to several human and animal pathogenic members of this complex including West Nile virus (WNV), Murray Valley Encephalitis virus (MVEV) and Japanese encephalitis virus (JEV) [1]
We identified four specific nucleotide substitutions in the 59 and 39 untranslated regions (UTRs) in the human isolate that were not present in the other USUV sequences
Bologna/09 and the corresponding long stable hairpin (LSH) domain with the relative free energy of the structure estimated as DG
Summary
Usutu virus (USUV), an arthropod-borne flavivirus within the Japanese encephalitis virus antigenic complex, is closely related to several human and animal pathogenic members of this complex including West Nile virus (WNV), Murray Valley Encephalitis virus (MVEV) and Japanese encephalitis virus (JEV) [1]. USUV is maintained in a typical enzootic cycle between mosquitoes and birds [2]. It was originally identified in South African mosquito species in 1959 but during the past .17 years, the virus has apparently dispersed out of Africa into Europe [3,4,5], presumably carried by migratory birds and their associated mosquitoes [6,7,8,9,10,11,12]. An elevated rate of USUV circulation was reported in vectors and birds in Italy [13,14,15,16].
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