Genetic diversity in the transmission-blocking vaccine candidate Plasmodium vivax gametocyte protein Pvs230 from the China-Myanmar border area and central Myanmar.

Genetic diversity in the transmission-blocking vaccine candidate Plasmodium vivax gametocyte protein Pvs230 from the China-Myanmar border area and central Myanmar.
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DOI:
10.1186/s13071-022-05523-0
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发表时间:
2022-10-17
影响因子:
3.2
通讯作者:
--
中科院分区:
医学2区
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性阶段表面抗原是传播阻断疫苗(TBVs)的潜在靶点。配子细胞和配子表面抗原P230是主要的TBV候选物,在脱毛和随后的卵囊发育过程中对红细胞结合至关重要。本文研究了中缅边境和缅甸中部地区间日疟原虫分离株Pvs230的遗传多样性。从CMB疟疾流行地区(143份)和缅甸(23份)的诊所采集间日疟原虫分离株。利用PCR扩增了Pvs230的种间可变部分(IVP,核苷酸1 ~ 807)和种间保守部分(ICP,核苷酸808 ~ 2862),并对其进行了测序。通过分子进化研究,对所研究的间日疟原虫种群和全球6个间日疟原虫种群的Pvs230序列的遗传多样性、选择特征、群体分化、单倍型网络和群体结构进行了评价。CMB (π = 0.002)和Myanmar (π = 0.001)分离株的遗传多样性有限。大多数氨基酸替换位于Pvs230的IVP和富含半胱氨酸的结构域。观察到IVP阳性选择和ICP纯化选择的证据。基于密码子的测试确定了IVP和ICP在自然选择下的特定密码子。东亚和东南亚居群的固定指数(FST)介于0.018 ~ 0.119之间,遗传分化程度较低。土耳其和巴布亚新几内亚种群间FST值最高(FST = 0.503)。在全球分离株中共鉴定出92个单倍型,其中主要的单倍型2和9最丰富,在东亚和东南亚人群中流行。在Pvs230的预测结构和b细胞表位上定位了几个检测到的非同义替换。我们在全球间日疟原虫种群中检测到Pvs230的遗传多样性水平较低。发现Pvs230具有地理特异性的单倍型。一些突变位于潜在的b细胞表位区域,需要在未来的TBV设计中加以考虑。在线版本包含补充材料,可在10.1186/s13071-022-05523-0获得。
Sexual stage surface antigens are potential targets of transmission-blocking vaccines (TBVs). The gametocyte and gamete surface antigen P230, a leading TBV candidate, is critical for red blood cell binding during exflagellation and subsequent oocyst development. Here, the genetic diversity of Pvs230 was studied in Plasmodium vivax parasite isolates from the China–Myanmar border (CMB) and central Myanmar. Plasmodium vivax isolates were collected in clinics from malaria-endemic areas of the CMB (143 samples) and Myanmar (23 samples). The interspecies variable part (IVP, nucleotides 1–807) and interspecies conserved part (ICP, 808–2862) of Pvs230 were amplified by PCR and sequenced. Molecular evolution studies were conducted to evaluate the genetic diversity, signature of selection, population differentiation, haplotype network, and population structure of the study parasite populations and publicly available Pvs230 sequences from six global P. vivax populations. Limited genetic diversity was observed for the CMB (π = 0.002) and Myanmar (π = 0.001) isolates. Most amino acid substitutions were located in the IVP and cysteine-rich domain of Pvs230. Evidence of positive selection was observed for IVP and purifying selection for ICP. Codon-based tests identified specific codons under natural selection in both IVP and ICP. The fixation index (FST) showed low genetic differentiation between East and Southeast Asian populations, with FST ranging from 0.018 to 0.119. The highest FST value (FST = 0.503) was detected between the Turkey and Papua New Guinea populations. A total of 92 haplotypes were identified in global isolates, with the major haplotypes 2 and 9 being the most abundant and circulating in East and Southeast Asia populations. Several detected non-synonymous substitutions were mapped in the predicted structure and B-cell epitopes of Pvs230. We detected low levels of genetic diversity of Pvs230 in global P. vivax populations. Geographically specific haplotypes were identified for Pvs230. Some mutations are located within a potential B-cell epitope region and need to be considered in future TBV designs. The online version contains supplementary material available at 10.1186/s13071-022-05523-0.
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