PXD014803-2

PXD014803 is an original dataset announced via ProteomeXchange.

Title	Up regulated Variant Surface Glycoproteins under TDP1 overexpression
Description	Trypanosoma brucei parasites successfully evade the host immune system by periodically switching the dense coat of Variant Surface Glycoproteins (VSG) at the cell surface. Each parasite expresses VSGs in a monoallelic fashion that is tightly regulated. The consequences of exposing multiple VSGs during an infection in terms of antibody response and disease severity remain unknown. In this study, we overexpressed a high mobility group box protein, TDP1, which was sufficient to open the chromatin of silent VSG expression sites, to disrupt VSG monoallelic expression and to generate viable and healthy parasites with a mixed VSG coat. Mice infected with these parasites mounted a multi-VSG antibody response, which rapidly reduced parasitemia. Consequently, we observed a prolonged mice survival in which nearly 90% of the mice survived a 30-day period infection with undetectable parasitemia. Immunodeficient RAG2 knock-out mice were unable to control the infection with TDP1-overexpressing parasites, showing that the adaptive immune response is critical to reduce disease severity. This study shows that simultaneous exposure of multiple VSGs is highly detrimental for the parasite even at the very early stages of infection, suggesting that drugs that disrupt VSG monoallelic expression could be used to treat trypanosomiasis.
HostingRepository	PRIDE
AnnounceDate	2019-09-13
AnnouncementXML	Submission_2019-10-25_05:21:37.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Douglas Lamont
SpeciesList	scientific name: Trypanosoma brucei; NCBI TaxID: 5691;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-29 04:36:36	ID requested
1	2019-09-13 09:44:29	announced
⏵ 2	2019-10-25 05:21:39	announced	2019-10-25: Updated publication reference for PubMed record(s): 31554700.
3	2024-10-22 04:57:56	announced	2024-10-22: Updated project metadata.

Aresta-Branco F, Sanches-Vaz M, Bento F, Rodrigues JA, Figueiredo LM, African trypanosomes expressing multiple VSGs are rapidly eliminated by the host immune system. Proc Natl Acad Sci U S A, 116(41):20725-20735(2019) [pubmed]

submitter keyword: VSG, Trypanosoma brucei, TDP1

Francisco Aresta Branco
contact affiliation	Division of Immune Diversity, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany & Division of Structural Biology of Infection and Immunity, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany
contact email	f.branco@dkfz-heidelberg.de
lab head
Douglas Lamont
contact affiliation	School of Life Sciences
contact email	d.j.lamont@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD014803
     1. Label: PRIDE project
     2. Name: Up regulated Variant Surface Glycoproteins under TDP1 overexpression