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エチオピアにおけるPlasmodium vivax Duffy Binding Proteinの頻発とその疫学的意義
Frequent expansion of Plasmodium vivax Duffy Binding Protein in Ethiopia and its epidemiological significance.
PMID: 31509523 PMCID: PMC6756552. DOI: 10.1371/journal.pntd.0007222.
抄録
ビバックス原虫のヒト赤血球への侵入は、ダッフィー抗原と相互作用するダッフィー結合タンパク質（PvDBP）に依存している。PvDBPのコピー数は、サハラ以南のアフリカで分離されたP. vivaxの間で異なることが最近明らかになった。しかし，PvDBPのコピー数の変動の程度，PvDBPの増殖の種類，および幅広いサンプル間での有意性はまだ明らかにされていない．エチオピアのP. vivax分離株178株を対象に，PCR法による診断法，新規の定量的リアルタイムPCR法，全ゲノムシークエンシング法を用いて，PvDBPの複製の有無，複製の種類，コピー数の変動を調べた．症状を呈した145検体について，95株のPvDBP重複が検出され，そのうち81株がカンボジア型，14株がマラガシ型のPvDBP重複を有していた．PvDBPの重複は1から4以上まで様々であった．PvDBPの重複を有する分離株は，無症候性感染症よりも症候性感染症の方が高率であった．33例の無症候性感染症では，2例中2例でPvDBPが2コピー検出され，いずれもカンボジア型の重複であった．Duffy陰性ヘテロ接合体のPvDBPコピー数はDuffy陽性と有意差はなく，コピー数の増加がDuffy陰性との特異的な関連性であるという仮説を支持するものではなかった．
Plasmodium vivax invasion of human erythrocytes depends on the Duffy Binding Protein (PvDBP) which interacts with the Duffy antigen. PvDBP copy number has been recently shown to vary between P. vivax isolates in Sub-Saharan Africa. However, the extent of PvDBP copy number variation, the type of PvDBP multiplications, as well as its significance across broad samples are still unclear. We determined the prevalence and type of PvDBP duplications, as well as PvDBP copy number variation among 178 Ethiopian P. vivax isolates using a PCR-based diagnostic method, a novel quantitative real-time PCR assay and whole genome sequencing. For the 145 symptomatic samples, PvDBP duplications were detected in 95 isolates, of which 81 had the Cambodian and 14 Malagasy-type PvDBP duplications. PvDBP varied from 1 to >4 copies. Isolates with multiple PvDBP copies were found to be higher in symptomatic than asymptomatic infections. For the 33 asymptomatic samples, PvDBP was detected with two copies in two of the isolates, and both were the Cambodian-type PvDBP duplication. PvDBP copy number in Duffy-negative heterozygotes was not significantly different from that in Duffy-positives, providing no support for the hypothesis that increased copy number is a specific association with Duffy-negativity, although the number of Duffy-negatives was small and further sampling is required to test this association thoroughly.