Dynamics of HIV-containing compartments in macrophages reveal sequestration of virions and transient surface connections.
During HIV pathogenesis, infected macrophages behave as "viral reservoirs" that accumulate and retain virions within dedicated internal Virus-Containing Compartments (VCCs). The nature of VCCs remains ill characterized and controversial. Using wild-type HIV-1 and a replication-competent HIV-1 carrying GFP internal to the Gag precursor, we analyzed the biogenesis and evolution of VCCs in primary human macrophages. VCCs appear roughly 14 hours after viral protein synthesis is detected, initially contain few motile viral particles, and then mature to fill up with virions that become packed and immobile. The amount of intracellular Gag, the proportion of dense VCCs, and the density of viral particles in their lumen increased with time post-infection. In contrast, the secretion of virions, their infectivity and their transmission to T cells decreased overtime, suggesting that HIV-infected macrophages tend to pack and retain newly formed virions into dense compartments. A minor proportion of VCCs remains connected to the plasma membrane overtime. Surprisingly, live cell imaging combined with correlative light and electron microscopy revealed that such connections can be transient, highlighting their dynamic nature. Together, our results shed light on the late phases of the HIV-1 cycle and reveal some of its macrophage specific features.
Institut Curie, Centre de Recherche, Paris, France.
Raphaël
R
Gaudin
Stefano
S
Berre
Bruna
B
Cunha de Alencar
Jérémie
J
Decalf
Michael
M
Schindler
François-Xavier
FX
Gobert
Mabel
M
Jouve
Philippe
P
Benaroch
D000328:Adult; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000648:ultrastructure / Q000821:virology*; D005110:Extracellular Space / Q000821:virology; D015497:HIV-1 / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D008264:Macrophages / Q000473:pathology* / Q000648:ultrastructure / Q000821:virology*; D008954:Models, Biological; D013997:Time Factors; D014771:Virion / Q000502:physiology* / Q000648:ultrastructure