Genetic polymorphism and natural selection in the C-terminal 42 kDa region of merozoite surface protein-1 among Plasmodium vivax Korean isolates
Jung-Mi Kang
0
Hye-Lim Ju
0
Yoo-Mi Kang
3
Dong-Hyun Lee
3
Sung-Ung Moon
2
Woon-Mok Sohn
0
Jae-Won Park
4
Tong-Soo Kim
1
Byoung-Kuk Na
0
0
Department of Parasitology and Institute of Health Sciences, Gyeongsang National University School of Medicine
,
Jinju 660-751
,
Korea
1
Department of Parasitology and Inha Research Institute for Medical Sciences, Inha University School of Medicine
,
Incheon 400-712
,
Korea
2
Department of Pathology, College of Medicine, Korea University
,
Seoul 136-705
,
Korea
3
Gyeongsang National University Graduate School of Medicine
,
Jinju 660-751
,
Korea
4
Department of Microbiology, Graduate School of Medicine, Gachon University of Medicine and Science
,
Incheon 406-799
,
Korea
Background: The carboxy-terminal 42 kDa region of Plasmodium vivax merozoite surface protein-1 (PvMSP-142) is a leading candidate antigen for blood stage vaccine development. However, this region has been observed to be highly polymorphic among filed isolates of P. vivax. Therefore it is important to analyse the existing diversity of this antigen in the field isolates of P. vivax. In this study, the genetic diversity and natural selection in PvMSP-142 among P. vivax Korean isolates were analysed. Methods: A total of 149 P. vivax-infected blood samples collected from patients in Korea were used. The region flanking PvMSP-142 was amplified by PCR, cloned into Escherichia coli, and then sequenced. The polymorphic characteristic and natural selection of PvMSP-142 were analysed using the DNASTAR, MEGA4 and DnaSP programs. Results: A total of 11 distinct haplotypes of PvMSP-142 with 40 amino acid changes, as compared to the reference Sal I sequence, were identified in the Korean P. vivax isolates. Most of the mutations were concentrated in the 33 kDa fragment (PvMSP-133), but a novel mutation was found in the 19 kDa fragment (PvMSP-119). PvMSP-142 of Korean isolates appeared to be under balancing selection. Recombination may also play a role in the resulting genetic diversity of PvMSP-142. Conclusions: PvMSP-142 of Korean P. vivax isolates displayed allelic polymorphisms caused by mutation, recombination and balancing selection. These results will be useful for understanding the nature of the P. vivax population in Korea and for development of a PvMSP-142 based vaccine against P. vivax.
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Background
Merozoite surface protein-1 (MSP-1) is a high molecular
mass protein abundantly expressed on the surface of the
merozoite of malaria parasites and it plays a critical role
in the erythrocyte invasion of the parasites [1]. It is
synthesized as a large precursor during schizogony and is
subsequently processed via proteolytic cleavage into four
major polypeptides of approximately 83, 30, 38, and
42 kDa from the N-terminus to C-terminus [1,2]. During
the invasion process, the C-terminal 42 kDa fragment
(MSP-142) is further processed into 33 kDa (MSP-133)
and 19 kDa (MSP-119) fragments, and the latter remains
on the merozoite surface and is carried into the invaded
erythrocytes, but all the other fragments are released
from the merozoite surface [3,4]. Individuals naturally
infected with Plasmodium vivax acquire humoral
immune responses against the C-terminal part of MSP-1,
MSP-119 or MSP-142 [5-10]. Antibodies that recognize
the C-terminal region of Plasmodium falciparum MSP-1
inhibit invasion of the merozoites into host erythrocytes
in vitro [11-14], and immunization of experimental
animals with MSP-119 confers protective immunity [15,16].
These findings demonstrate that MSP-142 is a
promising candidate antigen for blood stage vaccine
development [1,17-19]. However, genetic polymorphisms
encoding this region, within and among the P. vivax
population, are one of the important factors impeding
vaccine development.
Vivax malaria had been endemic on the Korean
Peninsula for centuries [20], but was eradicated in South
Korea by 1979 as a result of intensive efforts led by the
World Health Organization and Korean National
Malaria Eradication Programme. However, vivax malaria
reemerged in South Korea in 1993 and the outbreak has
continued with fluctuating numbers of annual
indigenous cases with the total number of cases up to 23,000
[21]. During the early period of the re-emergence, most
malaria cases were restricted to military personnel and
veterans who served near the Demilitarized Zone
(DMZ), and the geographic distribution was limited to
the DMZ and adjacent areas where no civilians reside
[22]. In spite of the significant decrease in the number of
malaria cases among military personnel since the
reemergence, mainly resulting from aggressive
chemoprophylaxis, the number of malaria cases in the civilian
population has increased and the geographic distribution
is expanding into southward cities and counties nearby
the DMZ, a pattern indicating the establishment of local
transmission in South Korea [21,23].
Although genetic polymorphisms in the central repeat
region of MSP-1 in Korean P. vivax isolates has been
previousl (...truncated)