Am nächsten ist es mit dem Zika-Virus verwandt, mit dem es eine Klade innerhalb der Moskito-übertragenen Flaviviren bildet.[12][13][14] Die epidemischen Varianten des Zika-Virus enthalten aus einer vergangenen Rekombination mit dem Spondweni-Virus einen gleichen Abschnitt im Protein NS2B des Zika-Virus.[15] Das Spondweni-Virus besitzt zwei Stämme, Chuku (Nigeria, 68 % identische RNA zum Zikavirus) und SA Ar 94 (Südafrika, 75 % identische RNA zum Zikavirus).[6]
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