Tihon Eliane, Rubio-Peña Karinna, Dujeancourt-Henry Annick, Crouzols Aline, Rotureau Brice, Glover Lucy
Trypanosome Molecular Biology, Institut Pasteur, Université Paris Cité, Paris, France.
Trypanosome Transmission Group, Trypanosome Cell Biology Unit, INSERM U1201 and, Institut Pasteur, Paris, France.
Front Cell Dev Biol. 2022 Apr 5;10:851475. doi: 10.3389/fcell.2022.851475. eCollection 2022.
The life cycle alternates between the tsetse fly vector and the mammalian host. In the insect, 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 expression in 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 expression we examined the role of VEX1 in this process. We show that modulating expression leads to a dysregulation of variant surface glycoprotein expression during metacyclogenesis, and that following both and 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.
生命周期在采采蝇媒介和哺乳动物宿主之间交替。在昆虫体内，它经历几个发育阶段，直到到达唾液腺并分化为循环后期形式，这种形式能够感染下一个哺乳动物宿主。哺乳动物的感染性取决于循环后期变体表面糖蛋白基因的表达，因为细胞发育成成熟的循环后期形式。VEX复合体对于血细胞形式中的单等位基因表达至关重要，然而，循环后期分化过程中表面蛋白基因表达的起始机制尚不清楚。为了更好地理解向成熟循环后期形式的转变以及循环后期表达的控制，我们研究了VEX1在此过程中的作用。我们表明，调节表达会导致循环后期发育过程中变体表面糖蛋白表达失调，并且在循环后期分化后，VEX1从前循环细胞中的多个核灶重新定位到循环后期细胞中的一到两个不同核灶——这种模式与在感染哺乳动物的血细胞形式中看到的模式相似。我们的数据表明VEX1在循环后期分化过程中发挥作用，以及它们对哺乳动物宿主具有感染性的能力。
