Reconstruction of the Evolutionary History and Dispersal of Usutu Virus, a Neglected Emerging Arbovirus in Europe and Africa

Abstract

Usutu virus (USUV), one of the most neglected Old World encephalitic flaviviruses, causes epizootics among wild and captive birds and sporadic infection in humans. The dynamics of USUV spread and evolution in its natural hosts are unknown. Here, we present the phylogeny and evolutionary history of all available USUV strains, including 77 newly sequenced complete genomes from a variety of host species at a temporal and spatial scaled resolution. The results showed that USUV can be classified into six distinct lineages and that the most recent common ancestor of the recent European epizootics emerged in Africa at least 500 years ago. We demonstrated that USUV was introduced regularly from Africa into Europe in the last 50 years, and the genetic diversity of European lineages is shaped primarily by in situ evolution, while the African lineages have been driven by extensive gene flow. Most of the amino acid changes are deleterious polymorphisms removed by purifying selection, with adaptive evolution restricted to the NS5 gene and several others evolving under episodic directional selection, indicating that the ecological or immunological factors were mostly the key determinants of USUV dispersal and outbreaks. Host-specific mutations have been detected, while the host transition analysis identified mosquitoes as the most likely origin of the common ancestor and birds as the source of the recent European USUV lineages. Our results suggest that the major migratory bird flyways could predict the continental and intercontinental dispersal patterns of USUV and that migratory birds might act as potential long-distance dispersal vehicles.

Widespread activity of multiple lineages of Usutu virus, western Europe, 2016

“…The geographically distinct lineages occurring in Europe are separated from each other by barriers such as climate, vegetation, different host species, and other unknown ecological conditions [5]. Nevertheless, the synchronous emergence of different USUV lineages in western Europe and their co-circulation in the same regions indicate similar basic ecological parameters driving the transmission of the different lineages involved in the recent outbreak.…”

Widespread Usutu virus outbreak in birds in the Netherlands, 2016

“…Although USUV circulated in neighbouring countries, it had not been detected in the Netherlands before 2016, despite scanning surveillance for bird mortality since 2008 and a targeted study in dead blackbirds based on convenience sampling in 2012 [1]. USUV emerged in Europe in Italy 20 years ago [6]; however, introductions from Africa probably started several decades earlier and continue to occur [7]. The virus has been detected in mosquitoes, birds and bats in eight European countries (Austria, Belgium, Czech Republic, Germany, Hungary, Italy, Spain, Switzerland) [7,8] and is presumably maintained in enzootic mosquito–bird transmission cycles.…”

“…USUV emerged in Europe in Italy 20 years ago [6]; however, introductions from Africa probably started several decades earlier and continue to occur [7]. The virus has been detected in mosquitoes, birds and bats in eight European countries (Austria, Belgium, Czech Republic, Germany, Hungary, Italy, Spain, Switzerland) [7,8] and is presumably maintained in enzootic mosquito–bird transmission cycles. Birds of 14 orders can be infected [8].…”

Usutu virus: current knowledge and future perspectives

“…21 Whether these changes affect the virus assembly or RNA replication is still unknown. Putative N-glycosylation sites (Asn-Xaa-Ser/Thr) have been identified at aa positions 118 and 154 of the E protein 3 and seem to be conserved among all USUV strains.…”