title: Centrosomal latency of incoming foamy viruses in resting cells.
abstract: Completion of early stages of retrovirus infection depends on the cell cycle. While gammaretroviruses require mitosis for proviral integration, lentiviruses are able to replicate in post-mitotic non-dividing cells. Resting cells such as naive resting T lymphocytes from peripheral blood cannot be productively infected by retroviruses, including lentiviruses, but the molecular basis of this restriction remains poorly understood. We demonstrate that in G0 resting cells (primary fibroblasts or peripheral T cells), incoming foamy retroviruses accumulate in close proximity to the centrosome, where they lie as structured and assembled capsids for several weeks. Under these settings, virus uncoating is impaired, but upon cell stimulation, Gag proteolysis and capsid disassembly occur, which allows viral infection to proceed. The data imply that foamy virus uncoating is the rate-limiting step for productive infection of primary G0 cells. Incoming foamy retroviruses can stably persist at the centrosome, awaiting cell stimulation to initiate capsid cleavage, nuclear import, and viral gene expression.
authors.affiliation: Université Paris 7, Paris, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Lehmann-Che
authors.forename: Noémie
authors.initials: N
authors.lastname: Renault
authors.forename: Marie Lou
authors.initials: ML
authors.lastname: Giron
authors.forename: Philippe
authors.initials: P
authors.lastname: Roingeard
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Clave
authors.forename: Joelle
authors.initials: J
authors.lastname: Tobaly-Tapiero
authors.forename: Patricia
authors.initials: P
authors.lastname: Bittoun
authors.forename: Antoine
authors.initials: A
authors.lastname: Toubert
authors.forename: Hugues
authors.initials: H
authors.lastname: de Thé
authors.forename: Ali
authors.initials: A
authors.lastname: Saïb
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002213:Capsid / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D018385:Centrosome / Q000821:virology*; D005347:Fibroblasts / Q000821:virology; D006801:Humans; D016192:Resting Phase, Cell Cycle; D016092:Spumavirus / Q000472:pathogenicity*; D017735:Virus Latency; D014779:Virus Replication