An Asian Origin for Subtype IV BK Virus Based on Phylogenetic Analysis

Similarly to other members of the Polyomaviridae family, BK virus (BKV) is thought to have co-evolved with its human host. BKV has four subtypes that are distinguishable by immunological reactivity, with two (subtypes I and IV) being most prevalent in human populations. Subtype I is the major subtype worldwide, whereas subtype IV is prevalent in East Asia and Europe but rare in Africa. The geographic distribution pattern of subtype IV BKV is in apparent disagreement with the hypothesis that BKV co-evolved with humans, since subtype IV rarely occurs in Africa. To elucidate the origin of subtype IV, 53 complete subtype IV sequences derived from East Asians and Europeans were subjected to a detailed phylogenetic analysis using the maximum-likelihood and neighbor-joining methods. We identified six subgroups (a1, a2, b1, b2, c1, and c2) that formed a tree represented by the formula: “(a1, a2), ((b1, b2), (c1, c2)).” Interestingly, we found a close correlation between subtype IV subgroups and population geography; thus, all subgroups except c2 were prevalent in particular East Asian populations, with c2 occurring in both Europe and Northeast Asia. From these findings, we conclude that subtype IV of BKV now prevalent in modern humans is derived from a virus that infected ancestral Asians. We introduce two hypotheses to explain how ancestral Asians became infected with subtype IV BKV. Reviewing Editor: Dr. Joshua Plotkin] Yuriko Nishimoto and Huai-Ying Zheng are two authors contributed equally to this article.