[Impact of polymorphisms in the C-terminal region of the HIV envelope on infection of primary cells]. (Doctoral thesis)

Original title: Rôle des polymorphismes dans la région C-Terminale de l’enveloppe du VIH dans l’infection de cellules primaires.
The human immunodeficiency virus (HIV) is responsible for the pandemic of acquired immunodeficiency syndrome (AIDS). Being highly variable, the virus has been subdivided into viral subtypes. Subtype B is the most studied, while subtype C is the most spread. The envelope (Env) expressed at the surface of the virion enables infection of cells involved in the immune system, like CD4 cells (CD4 TL) and macrophages. We studied the Env region not exposed at the viral surface (intraviral tail, gp41CT), which also harbors sequence characteristics linked to viral subtype. Viruses with subtype C gp41CT had lower replication capacities in CD4 TL. Microscopy analysis showed a defect in clustering of the viral structural protein Gag, revealing that changes in gp41CT affect assembly of all viral components. This defect was seen in CD4 TL but not in macrophages, suggesting the involvement of a cellular factor. Identifying this factor could open new therapeutic leads.