The HIV-1-containing macrophage compartment: a perfect cellular niche?

• HIV-1 assembles, buds, and is stored in the virus-containing compartment (VCC), which is found in myeloid-lineage immune cells.
• The VCC is inside the cell but is frequently connected to the outside environment.
• Antibodies cannot efficiently access virus within the VCC.
• HIV-1 may move rapidly from the VCC to contact permissive cells for cell-to-cell spread.

Macrophages are a major target of HIV-1 infection and are believed to act as viral reservoirs and mediators of HIV-1-associated neurological damage. These pathological roles may be associated with the ability of the virus to assemble and accumulate in apparently intracellular compartments in macrophages. These so-called virus-containing compartments were initially thought to be late endosomes or multivesicular bodies, but it has since been shown that they are distinct structures that have complex three-dimensional morphology, a unique set of protein markers, and features such as a near-neutral pH and frequent connections to the extracellular milieu. These features appear to protect HIV-1 from hostile elements both within and outside the cell. This review discusses the cellular and molecular characteristics of HIV-1-containing compartments in macrophages and how they offer a safe haven for the virus, with important consequences for pathogenesis.