INFILTRINS AS A NEW CLASS OF PATHOGEN-SECRETED, HOST NUCLEUS INFILTRATING PROTEINS IN TREMATODES

Research output: Contribution to conferenceAbstractpeer-review

Abstract

Infiltrins (short for pathogen-secreted host nucleus infiltrating proteins) are
proteins secreted by specific stages of trematode parasites, which are in
close contact with host tissues. Such infiltrins have the ability to enter host
cells by yet to be described mechanisms, and from there rapidly translocate
to the nucleus. The archetypal infiltrin is M-IPSE (a.k.a. IPSE/alpha-1), a
glycoprotein secreted by Schistosoma mansoni eggs, characterised by the
simultaneous presence of a classical secretory and a nuclear localisation
signal (CSS/NLS) signal. Within minutes following uptake by mammalian
host cells, M-IPSE translocates to the nucleus and binds to DNA. This
suggests that infiltrins, by acting e.g. as transcription factors, might play
a central role in controlling the host-parasite relationship at the molecular
level. Together with their secretory status, this role makes infiltrins
interesting targets for vaccination. Here, we demonstrate similar properties
for H-IPSE, the homologue of M-IPSE in Schistosoma haematobium. We
first generated a series of truncated constructs fused with AcGFP1, which
were transfected into mammalian cells. Nuclear localisation of fluorescence
confirmed the existence of a single, monopartite NLS located near the
C-term of H-IPSE. The predicted H-IPSE ‘SKRRRKY’ NLS motif, inserted
into Tetra-EGFP, but not an Alanine NLS mutant, redirected the encoded
approx. 100 kDa protein entirely to the nucleus. More importantly,
wildtype recombinant H-IPSE, added exogenously to HTB-9 bladder
carcinoma cells, fully translocated to the nucleus, whereas the Alanine NLS
mutant remained in the cytoplasm. Similarly, Fasciola hepatica proteins
H2A and GST-sigma were able to enter Huh7 hepatocarcinoma cells and
translocate to the nucleus. We have scanned the F. hepatica genome
with a stringent approach designed to detect genes encoding dual CSS/
NLS functionality and identified several other potential infiltrins. Overall,
the existence of infiltrins in S. mansoni, S. haematobium and F. hepatica
suggests that these proteins may represent a more general regulatory
principle operating in parasitic trematodes.
Original languageEnglish (Ireland)
Publication statusPublished - 2017
Event66TH AMERICAN SOCIETY TROPICAL MEDICINE & HYGIENE - Baltimore , United States
Duration: 05 Nov 201709 Nov 2017

Conference

Conference66TH AMERICAN SOCIETY TROPICAL MEDICINE & HYGIENE
Country/TerritoryUnited States
Period05/11/201709/11/2017

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