| dc.description.abstract |
<p>The sickle-cell trait hemoglobin genotype (HbAS) is known to protect against severe
malaria caused by Plasmodium falciparum. However, the biological mechanisms behind
this protection are not well understood. Cyclophilin 19B (PfCyP-19B) is a parasitic
gene that produces the protein cyclophilin 19B, a member of the unfolded protein response
that is important in parasitic protein folding and trafficking. We set out to measure
the transcript expression level of PfCyP-19B to investigate its potential role in
the mechanisms that confer protection for HbAS individuals. RNA was extracted from
both in vivo samples collected from Malian children as well as in vitro samples harvested
throughout a 48-hour incubation period. RNA extracts were reverse transcribed and
transcript expression was measured via qPCR. Wilcoxon rank sum and bootstrapping methods
were used to analyze transcript units between parasites grown in normal (HbAA) and
HbAS red blood cells. The results from our cross-sectional in vivo data revealed under
expression of PfCyP-19B among individuals with the HbAS genotype compared to those
with the HbAA genotype (Wilcoxon rank sum p=0.006). In vitro time series results showed
no significant difference in PfCyP-19B transcript expression levels between genotypes
but did display a 24-hour pattern of peak expression for both HbAA and HbAS genotypes.
The under expression of PfCyP-19B among HbAS individuals could be linked to impaired
protein trafficking, interfering with the parasite’s ability to display surface proteins
vital for cytoadherence and severe disease manifestation. The 24-hour peak transcript
expression displayed in vitro roughly aligns with the P. falciparum parasite stage
transition states, suggesting cyclophilin 19B may aid in parasitic transitions.</p>
|
|
