Research Center for Infectious Disease Control, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, 565-0871, Japan.
Department of Malaria Vaccine Development, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, 565-0871, Japan.
Parasit Vectors. 2020 Apr 6;13(1):170. doi: 10.1186/s13071-020-04044-y.
Serine repeat antigen (SERA) is conserved among species of the genus Plasmodium. Sera genes form a multigene family and are generally tandemly clustered on a single chromosome. Although all Plasmodium species encode multiple sera genes, the number varies between species. Among species, the members share similar sequences and gene organization. SERA possess a central papain-like cysteine protease domain, however, in some members, the active site cysteine residue is substituted with a serine. Recent studies implicate this gene family in a number of aspects in parasite biology and induction of protective immune response. This review summarizes the current understanding on this important gene family in several Plasmodium species. The Plasmodium falciparum (Pf)-sera family, for example, consists of nine gene members. Unlike other multigene families in Plasmodium species, Pf-sera genes do not exhibit antigenic variation. Pf-sera5 nucleotide diversity is also low. Moreover, although Pf-sera5 is highly transcribed during the blood stage of malaria infection, and a large amount is released into the host blood following schizont rupture, in malaria endemic countries the sero-positive rates for Pf-SERA5 are low, likely due to Pf-SERA5 binding of host proteins to avoid immune recognition. As an antigen, the N-terminal 47 kDa domain of Pf-SERA5 is a promising vaccine candidate currently undergoing clinical trials. Pf-SERA5 and Pf-SERA6, as well as P. berghei (Pb)-SERA3, and Pb-SERA5, have been investigated for their roles in parasite egress. Two P. yoelii SERA, which have a serine residue at the protease active center, are implicated in parasite virulence. Overall, these studies provide insight that during the evolution of the Plasmodium parasite, the sera gene family members have increased by gene duplication, and acquired various functions that enable the parasite to survive and successfully maintain infection in the host.
血清重复抗原（SERA）在疟原虫属的物种中是保守的。血清基因形成一个多基因家族，通常串联簇集在一条染色体上。尽管所有的疟原虫物种都编码多个血清基因，但数量在物种间有所不同。在物种间，这些成员具有相似的序列和基因组织。SERA 具有一个中央木瓜蛋白酶样半胱氨酸蛋白酶结构域，但在一些成员中，活性位点半胱氨酸残基被丝氨酸取代。最近的研究表明，这个基因家族在寄生虫生物学和诱导保护性免疫反应的许多方面都有作用。这篇综述总结了目前对几种疟原虫物种中这一重要基因家族的理解。例如，恶性疟原虫（Pf）-血清家族由九个基因成员组成。与疟原虫物种中的其他多基因家族不同，Pf 血清基因不表现抗原变异。Pf 血清 5 的核苷酸多样性也较低。此外，尽管 Pf 血清 5 在疟疾感染的血液阶段高度转录，并在裂殖体破裂后大量释放到宿主血液中，但在疟疾流行国家，Pf-SERA5 的血清阳性率较低，这可能是由于 Pf-SERA5 与宿主蛋白结合以避免免疫识别。作为一种抗原，Pf-SERA5 的 N 端 47 kDa 结构域是目前正在进行临床试验的有前途的疫苗候选物。Pf-SERA5 和 Pf-SERA6 以及 P. berghei（Pb）-SERA3 和 Pb-SERA5 的研究表明它们在寄生虫逸出中的作用。两个 Pf 血清，其中一个在蛋白酶活性中心有一个丝氨酸残基，被认为与寄生虫的毒力有关。总的来说，这些研究表明，在疟原虫寄生虫的进化过程中，血清基因家族成员通过基因复制增加，并获得了各种功能，使寄生虫能够在宿主中生存并成功维持感染。
