Additional remarks phenotype | Mutant/mutation
The mutant expresses a mutated PBANKA_0112100, in which T-to-C transition at position 5468 is introduced. This mutation results resulted in a change of a serine (S) into phenylalanine (F).
Protein (function)
A member of the apicomplexan homolog of plant Apetela2 (ApiAP2) transcription factor (TF) family.
There are 26 members of the ApiAP2 TF family, and despite their similarities, each has unique features in terms of their DNA recognition motifs and their expression patterns during the life cycle of Plasmodium, suggesting distinct functional properties. PBANKA_011210 (referred to here as ApiAP2) is a Pb ApiAP2 family member predominantly expressed in schizonts in the blood stage of the parasite infection in mice and appears to be essential as Pb parasites, in which the gene encoding ApiAP2 was knocked out, were not viable.
Recent comparative genetic screening of rodent Plasmodium strains revealed a non-synonymous SNP (a T-to-C transition at position 5468) in the first DNA binding domain of the ApiAP2 gene. This SNP resulted in a phenylalanine (F) in PbANKA and PbSP11 strains and a serine (S) in PbNK65 and PbK173 strains at amino acid position 1823 of the ApiAP2 protein. Given that this polymorphism is located in the ApiAP2 DNA binding domain and that the biochemical differences between phenylalanine, a hydrophobic aromatic amino acid, and serine, a hydrophilic amino acid, we postulated that these two genes may encode functionally different ApiAP2 proteins.
Here, we provide evidence that the two polymorphic forms of ApiAP2 do bind to different DNA motifs, resulting in altered transcriptional profiles, and that infections of mice by PbNK65F versus PbNK65S result in markedly different host immune responses, one that is protective and one that is not.
Phenotype
Evidence is presented that:
PbNK65F infections resulted in an early interferon-γ response and a later expansion of germinal centers, resulting in high levels of infected red blood cell–specific TH1-type immunoglobulin G2b (IgG2b) and IgG2c antibodies.
Additional information
From the Abstract:
'Here, we show that a single-nucleotide polymorphism (SNP) resulting in a single amino acid change (S to F) in an ApiAP2 transcription factor in the rodent malaria parasite Plasmodium berghei (Pb) NK65 allowed infected mice to mount a T helper cell 1 (TH1)–type immune response that controlled subsequent infections. As compared to PbNK65S, PbNK65F parasites differentially expressed 46 genes, most of which are predicted to play roles in immune evasion. PbNK65F infections resulted in an early interferon-γ response and a later expansion of germinal centers, resulting in high levels of infected red blood cell–specific TH1-type immunoglobulin G2b (IgG2b) and IgG2c antibodies.
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