A multigene analysis of the phylogenetic relationships among the flaviviruses (Family: Flaviviridae) and the evolution of vector transmission

Abstract

Summary. The genus Flavivirus (family Flaviviridae) presently comprises around 70 single-strand positive-sense RNA viruses. These replicate in a range of vertebrate and invertebrate cells and may be mosquito-borne, tick-borne or have no-known-vector. Since transmission mode correlates strongly with phylogeny, the flaviviruses constitute a valuable model for the evolution of vectorborne disease. Attempts to resolve the higher-level taxonomic relationships of the flaviviruses through molecular phylogenetics have thus far proved inconclusive because of conflicting positions for the three main transmission groups. We conducted the most comprehensive phylogenetic study to date, involving maximum likelihood analyses of the NS3 and NS5 genes and the entire genome sequences available at present. For the first time, we use and test a variety of more robust methods of sequence alignment and appropriate models of amino acid replacement to study these highly divergent sequences, and explicitly test specific hypotheses of tree topology. We show that (i) the NS5 gene contains insufficient phylogenetic signal to choose between competing topological hypotheses, (ii) the NS3 gene and whole genome data indicate that the mosquito-borne flaviviruses represent an outgroup to the remaining flaviviruses, and (iii) that tick-borne transmission is probably a derived trait within the genus.

Molecular-based identification and phylogeny of genomic and proteomic sequences of mosquito-borne flavivirus

“…The tree topologies generated from the NJ and MP methods ( Fig. 1a) was correlated closely to those previously reported tree (Billoir et al 2000;Cook and Holmes 2006;Kuno and Chang 2006;Medeiros et al 2007;Grard et al 2007). The unrooted phylogenetic tree was clustered into three groups and to investigation of deepest nodes assumed that the tree separated into six clades namely, AROAV, DNEV, JEV, KOKV, NTAV and YFV.…”

“…Despite these extensive data, there have been few previous attempts to correlate molecular evolution with epidemiological and ecological features of MBFVs. The phylogenetic trees presented here have extended previous analyses of the flavivirus NS5 (Kuno et al 1998;Billoir et al 2000), E gene (Marin et al 1995), full genome and NS3 phylogenetic trees (Cook and Holmes 2006). By mapping these biological characteristics onto the trees, the phylogenetic study presented in this paper demonstrates a striking series of associations between molecular phylogeny and vector responsible for transmission of virus.…”

“…The brackets denote the virus cluster and the red color stand for the virus caused encephalitic disease and transmitted by culex mosquito vector; green color denotes the virus causes haemorrhagic disease and transmitted through aedes mosquito Genes Genom (2014) 36:31-43 39 antigenic cross reactivity in neutralization, complement fixation and haemagglutination inhibition tests (Madrid and Porterfield 1974;Calisher et al 1989). Several other studies (Kuno et al 1998;Gaunt et al 2001;Cook and Holmes 2006;Billoir et al 2000) were conducted using sequences of individual genes and/or ORF to investigate Fig. 2 Phylogenetic analysis based on gene sequence of E protein, NS3 and NS5 protein sequences specified with (a), (b) and (c) respectively.…”

Complete genome characterization of Rocio virus (Flavivirus: Flaviviridae), a Brazilian flavivirus isolated from a fatal case of encephalitis during an epidemic in São Paulo state

“…Numerous phylogenetic studies (Billoir et al, 2000;Cook & Holmes, 2005;Gould et al, 2003;Kuno et al, 1998Kuno et al, , 2005 have been conducted using sequences of individual genes and/or ORF to investigate the flavivirus genetic relationship. These studies generated basically two contrasting phylogenies, NS5 gene tree and NS3/ORF tree.…”

Sequence signatures in envelope protein may determine whether flaviviruses produce hemorrhagic or encephalitic syndromes

“…Flaviviruses are classified into three main groups: tickborne flaviviruses, mosquito-borne flaviviruses, and flaviviruses with no known vector [1]. Flaviviruses naturally pathogenic to humans are found among both the tick-borne and mosquito-borne groups.…”