The VEX complex regulates mVSG expression during the transition to mammalian infectivity in Trypanosoma brucei

The Trypanosoma 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 mammalian host. Mammalian infectivity is dependent on expression of the metacyclic variant surface glycoprotein genes in the mature metacyclic. The VEX complex of proteins are essential for monoallelic variant surface glycoprotein expression in Trypanosoma 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 metacyclic 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. We show that following both in vivo and in vitro metacyclic differentiation, VEX1 relocalises from multiple foci in procyclic cells to 1 – 2 distinct foci in metacyclic cells - a pattern like that seen in mammalian infective bloodstream forms. Our data suggest a role for the VEX complex in metacyclic differentiation process their capacity to become infectious to the mammalian host.