Immunodeficiency virus uptake, turnover, and 2-phase transfer in human dendritic cells.
HIV-1 subverts antigen processing in dendritic cells (DCs) resulting in viral uptake, infection, and transfer to T cells. Although DCs bound monomeric gp120 and HIV-1 similarly, virus rarely colocalized with endolysosomal markers, unlike gp120, suggesting HIV-1 alters endolysosomal trafficking. Virus within DC intracellular compartments rapidly moved to DC-CD4+ lymphocyte synapses when introduced to CD4+ lymphocyte cultures. Although viral harboring and transfer from nonlysosomal compartments was transient, given DC-associated virus protein, nucleic acids, and infectious HIV-1 transfer to CD4+, lymphocytes decayed within 24 hours. However a second long-term transfer phase was apparent in immature DCs after 48 hours as a zidovudine-sensitive rise in proviral DNA. Therefore, DCs transfer HIV-1 to CD4+ lymphocytes in 2 distinct phases. Immature and mature DCs first divert virus from the endolysosomal pathway to the DC-T-cell synapse. Secondly, the later transfer phase from immature DCs is through de novo HIV-1 production. Thus, the controversy of DCs being infected or not infected for the mechanics of viral transfer to CD4+ lymphocytes can be addressed as a function of time.
Turville
Stuart G
SG
Centre for Virus Research, Westmead Millennium Institute, Sydney, Australia.
Santos
John J
JJ
Frank
Ines
I
Cameron
Paul U
PU
Wilkinson
John
J
Miranda-Saksena
Monica
M
Dable
Joanne
J
Stössel
Hella
H
Romani
Nikolaus
N
Piatak
Michael
M
Lifson
Jeffrey D
JD
Pope
Melissa
M
Cunningham
Anthony L
AL
D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000648:ultrastructure / Q000821:virology*; D004220:Disulfides; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000254:growth & development* / Q000276:immunology*; D006801:Humans; D008854:Microscopy, Electron; D011485:Protein Binding; D021381:Protein Transport; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D013439:Sulfhydryl Reagents
D004220:Disulfides; D015699:HIV Envelope Protein gp120; D013439:Sulfhydryl Reagents; C001105:2,2'-dipyridyl disulfide; D015082:2,2'-Dipyridyl