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In recent years, considerable progress was made in identifying host-cell-interacting partners for Nef, and the molecular machinery used by Nef to interfere with protein trafficking has started to be unraveled.

Here, we briefly review the knowledge gained and discuss new findings regarding the mechanisms by which Nef modifies the intracellular trafficking pathways to prevent antigen presentation, facilitate viral particle release and enhance the infectivity of HIV-1 virions.

Nef is abundantly expressed early in infection and is thought to optimize the cellular environment for viral replication.

To exert these functions, Nef physically interacts with host proteins that regulate protein trafficking.

The Nef protein of the human immunodeficiency virus is a crucial determinant of viral pathogenesis and disease progression.

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Nef controls expression levels of various cell surface molecules that play important roles in immunity and virus life cycle, by directly interfering with the itinerary of these proteins within the endocytic and late secretory pathways.

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