Transcriptome analysis of diverse Plasmodium falciparum clinical isolates identifies genes correlating with highly variable expression of merozoite surface protein MSPDBL2
Transcriptome analysis of diverse Plasmodium falciparum clinical isolates identifies genes correlating with highly variable expression of merozoite surface protein MSPDBL2
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对多种恶性疟原虫临床分离株的转录组分析鉴定了与裂殖子表面蛋白 MSPDBL2 高度可变表达相关的基因
DOI：
10.1101/2022.02.18.481051
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Hocking S
中科院分区：
文献类型：
--
作者：
Hocking S
恶性疟原虫裂殖子表面蛋白MSPDBL2处于强平衡选择下，并且是天然获得的抗体的靶标。值得注意的是，MSPDBL 2仅在任何培养的寄生虫系的少数成熟胚胎中表达，并且mspdbl 2基因转录响应于配子体发育诱导剂GDV 1的过表达而增加，因此理解其天然表达是重要的。在这里，MSPDBL 2在成熟的大肠杆菌中进行了分析，在第一个活体培养周期的96个临床分离株从四个人口不同程度的感染地方病在不同的西非国家，免疫荧光显微镜与抗体对保守的蛋白质区域。在大多数分离株中，不到1%的成熟突变体对MSPDBL2呈阳性（总体中位数为0.6%），但频率分布高度偏斜，因为9个分离株的突变体阳性率超过3%，1个分离株的阳性率为73%。为了研究其他基因位点的表达是否与MSPDBL2表达相关，对来自17个临床分离株的富集有大量阳性外显子的材料进行全转录组测序。特定寄生虫基因的转录物与寄生虫中的MSPDBL 2阳性以及MSPDBL 2基因转录物水平高度显著正相关，其中先前涉及的可能参与配子体发生的基因过度表达，但不包括配子体发生主调节因子ap2g。虽然MSPDBL2显然不直接参与性承诺，但它标志着一个共同发生的发育亚群，在血液阶段感染中可能在功能上不同。
The merozoite surface protein MSPDBL2 ofPlasmodium falciparumis under strong balancing selection and is a target of naturally acquired antibodies. Remarkably, MSPDBL2 is expressed in only a minority of mature schizonts of any cultured parasite line, andmspdbl2gene transcription increases in response to overexpression of the gametocyte development inducer GDV1, so it is important to understand its natural expression. Here, MSPDBL2 in mature schizonts was analysed in the firstex vivoculture cycle of 96 clinical isolates from four populations with varying levels of infection endemicity in different West African countries, by immunofluorescence microscopy with antibodies against a conserved region of the protein. In most isolates, less than 1% of mature schizonts were positive for MSPDBL2 (median of 0.6% overall), but the frequency distribution was highly skewed as nine isolates had more than 3% schizonts positive and one had 73% positive. To investigate whether expression of other gene loci correlated with MSPDBL2 expression, whole transcriptome sequencing was performed on schizont-enriched material from 17 of the clinical isolates with a wide range of proportions of schizonts positive. Transcripts of particular parasite genes were highly significantly positively correlated with MSPDBL2 positivity in schizonts as well as withmspdbl2gene transcript levels, with overrepresentation of genes previously implicated as likely to be involved in gametocytogenesis, but not including the gametocytogenesis master regulatorap2g. Although MSPDBL2 is apparently not directly involved in sexual commitment, it marks a co-occurring developmental subpopulation that may be functionally distinct within blood stage infections.
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影响因子：
10.7
作者：
Ochola LI;Tetteh KK;Stewart LB;Riitho V;Marsh K;Conway DJ
通讯作者：
Conway DJ
疟原虫恶性疟原虫临床分离株和实验室适应克隆之间的裂殖体转录组变异
影响因子：
4.4
作者：
Sarah J Tarr;Ofelia Díaz;L. Stewart;S. Hocking;Lee Murray;Craig W. Duffy;T. Otto;L. Chappell;J. Rayner;G. Awandare;D. Conway
通讯作者：
D. Conway
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影响因子：
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作者：
U. Böhme;T. Otto;M. Sanders;C. Newbold;M. Berriman
通讯作者：
M. Berriman
影响因子：
3.1
作者：
Tetteh KK;Osier FH;Salanti A;Kamuyu G;Drought L;Failly M;Martin C;Marsh K;Conway DJ
通讯作者：
Conway DJ
影响因子：
3.7
作者：
Singh S;Soe S;Weisman S;Barnwell JW;Pérignon JL;Druilhe P
通讯作者：
Druilhe P