VEX1 Influences mVSG Expression During the Transition to Mammalian Infectivity in Trypanosoma brucei

Abstract

The Trypanosoma (T) brucei life cycle alternates between the tsetse fly vector and the mammalian host. In the insect, T. brucei undergoes several developmental stages until it reaches the salivary gland and differentiates into the metacyclic form, which is capable of infecting the next mammalian host. Mammalian infectivity is dependent on expression of the metacyclic variant surface glycoprotein genes as the cells develop into mature metacyclics. The VEX complex is essential for monoallelic variant surface glycoprotein expression in T. brucei bloodstream form, however, initiation of expression of the surface proteins genes during metacyclic differentiation is poorly understood. To better understand the transition to mature metacyclics and the control of metacyclic variant surface glycoprotein expression we examined the role of VEX1 in this process. We show that modulating VEX1 expression leads to a dysregulation of variant surface glycoprotein expression during metacyclogenesis, and that following both in vivo and in vitro metacyclic differentiation VEX1 relocalises from multiple nuclear foci in procyclic cells to one to two distinct nuclear foci in metacyclic cells - a pattern like the one seen in mammalian infective bloodstream forms. Our data suggest a role for VEX1 in the metacyclic differentiation process and their capacity to become infectious to the mammalian host.

An allele-selective inter-chromosomal protein bridge supports monogenic antigen expression in the African trypanosome

“…VSG exclusion factor 2 (VEX2) 19 associates with VEX1 in a transcription-dependent manner within a VSG transcription and RNA trans -splicing subcompartment, orchestrating both single allele choice and the exclusion of other VSGs 13 , 19 – 21 . Here, we show that VEX2 is a VSG allele-selective and self-limiting factor that, with VEX1, forms a physical bipartite inter-chromosomal bridge to support multi-allelic exclusion.…”

Structural and Immunological Similarities Between the Metacyclic and Bloodstream Form Variant Surface Glycoproteins of the African Trypanosome

“…T. brucei PCF 29-13 cells were transfected by plasmid that encodes for tetracyclineinducible RBP6 overexpression (kindly gifted by Lucy Glover, Institute Pasteur, Paris, France, (Tihon et al, 2022)). The cells were cultured in SDM-80 media (SDM-79 without glucose).…”