Cited by 165Malaria Research and ControlBlood groups and transfusionBird parasitology and diseases

Global genetic diversity and evolution of var genes associated with placental and severe childhood malaria

Trimnell, Adama R., Kraemer, Susan M., Mukherjee, Sandeep, Phippard, David J., Janes, Joel H., Flamoe, Eric, Su, Xin-zhuan, Awadalla, Philip +1 more·2006·Molecular and Biochemical Parasitology

Abstract

In Plasmodium falciparum, var genes encode adhesive proteins that are transported to the surface of infected erythrocytes and act as major virulence determinants for infected erythrocyte binding and immune evasion. Var genes are highly diverse and can be classified into five major groups (UpsA, B, C, D, and E). Previous serological studies have suggested that the UpsA var group may contain common antigenic types that have important roles in severe childhood malaria. Here, our analysis found that UpsA vars are highly diverse between 22 world-wide parasite isolates, although they could be grouped into two broad clusters that may be separately recombining. By comparison, orthologs of the UpsA-linked Type 3 var and UpsE-linked var2csa were detected in nearly all parasite isolates, and a var2csa ortholog was also present in a chimpanzee malaria P. reichenowi that diverged from P. falciparum approximately 5-7 million years ago. Although the specific function of Type 3 var genes is unknown, var2csa is a leading candidate for a pregnancy associated malaria vaccine. Compared to typical var genes, var2csa is unusually conserved but still had only 54-94% amino acid identity in extracellular binding regions. However, var2csa alleles have extensive gene mosaicism within polymorphic blocks that are shared between world-wide parasite isolates and recognizable in P. rechenowi suggesting a high rate of self-self recombination and an ancient and globally-related pool of var2csa polymorphism. T…

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Crossref · 10.1016/j.molbiopara.2006.03.012

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  • VAR2CSA shows substantial sequence and structure conservation between isolates, which could explain the geographical independence of antibody responses to the VSA expressed by iEs from pregnant women.

    “VAR2CSA show substantial sequence and structure conservation between isolates (Trimnell et al. , 2006), which could explain the geographical independence of antibody responses to the VSA expressed by iEs from pregnant women.”

    From Towards a vaccine against pregnancy-associated malaria (2008) · cites this paper as Trimnell et al., 2006

  • Analysis of var2csa from field isolates has revealed alternating areas of substantial interclonal polymorphism.

    “but analysis of var2csa from field isolates has revealed alternating areas of substantial interclonal polymorphism (Dahlback et al. , 2006; Trimnell et al. , 2006).”

    From Towards a vaccine against pregnancy-associated malaria (2008) · cites this paper as Trimnell et al., 2006

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Authors
Trimnell, A. R., Kraemer, S. M., Mukherjee, S., Phippard, D. J., Janes, J. H., Flamoe, E., Su, X.-Z., Awadalla, P., & Smith, J. D.
Affiliations
  • Center for Infectious Disease Research (US)
  • National Institutes of Health (US)
  • North Carolina State University (US)
Corresponding author
  • Awadalla, Philip
  • Smith, Joseph D.
Venue
Molecular and Biochemical Parasitology
Publisher
Elsevier BV
Published
2006-08
Volume
148
Issue
2
Pages
169-180
ISSN
0166-6851 (ISSN-L)
OpenAlex
W1996773860
Cited by
165
References
57
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 6 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 8 · 2016: 1 · 2015: 8 · 2014: 14 · 2013: 11 · 2012: 14
FWCI
19.64
Type
journal article
Language
en
Open access
closed
Locations
  • Molecular and Biochemical Parasitology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Wellcome Trust
  • European Commission
  • National Institute of Allergy and Infectious Diseases (R01AI047953, R01 AI4795301A1)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Health Sciences › Medicine › Hematology › Blood groups and transfusion
  • Life Sciences › Immunology and Microbiology › Parasitology › Bird parasitology and diseases
Keywords
Plasmodium falciparum, var genes, VAR2CSA, placental malaria, Plasmodium reichenowi, erythrocyte adhesion, immune evasion
MeSH terms
Amino Acid Sequence, Animals, Antigenic Variation, Child, Female, Humans, Molecular Sequence Data, Placenta, Placenta Diseases, Plasmodium falciparum, Pregnancy, Severity of Illness Index, Genetic Variation, Pregnancy Complications, Parasitic, Malaria, Falciparum, Genes, Protozoan, Sequence Analysis, DNA, Evolution, Molecular

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