Major histocompatibility complex class‐ II molecules promote targeting of human immunodeficiency virus type 1 virions in late endosomes by enhancing internalization of nascent particles from the plasma membrane

Summary Productive assembly of human immunodeficiency virus type 1 ( HIV ‐1) takes place, primarily, at the plasma membrane. However, depending on the cell types, a significant proportion of nascent virus particles are internalized and routed to late endosomes. We previously reported that expression of human leucocyte antigen ( HLA )‐ DR promoted a redistribution of G ag in late endosomes and an increased detection of mature virions in these compartments in H e L a and human embryonic kidney 293 T model cell lines. Although this redistribution of G ag resulted in a marked decrease of HIV ‐1 release, the underlying mechanism remained undefined. Here, we provide evidence that expression of HLA‐DR at the cell surface induces a redistribution of mature G ag products into late endosomes by enhancing nascent HIV ‐1 particle internalization from the plasma membrane through a process that relies on the presence of intact HLA‐DR α and β‐chain cytosolic tails. These findings raise the possibility that major histocompatibility complex class‐ II molecules might influence endocytic events at the plasma membrane and as a result promote endocytosis of progeny HIV ‐1 particles.