Low-level HIV infection of plasmacytoid dendritic cells: onset of cytopathic effects and cell death after PDC maturation.
Plasmacytoid dendritic cells (PDC), the natural type-1 interferon (IFN) producing cells, are part of the innate immune defense against human immunodeficiency virus (HIV). PDC numbers are reduced in advanced stages of infection. These cells can be infected in vivo by HIV since highly purified PDC showed evidence of infectious HIV. Moreover, when PDC derived from uninfected donors were exposed to high-titered HIV isolates, productive infection occurred although with low-level replication. Using real-time amplification, PDC and unstimulated CD4+ cells were found equally susceptible to HIV infection; however, HIV replication was considerably limited in the PDC. Virus replication was enhanced after PDC treatment with CD40L and antibodies against IFN-alpha, most likely reflecting the reduction in IFN-alpha activity. On maturation, the infected PDC showed multinuclear cell syncytia formation and death. These findings indicate that PDC can be reservoirs for HIV dissemination and that HIV infection of PDC can contribute to their decline.
Schmidt
Barbara
B
Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, CA 94143-0128, USA.
Scott
Iain
I
Whitmore
Robert G
RG
Foster
Hillary
H
Fujimura
Sue
S
Schmitz
Juergen
J
Levy
Jay A
JA
D000906:Antibodies / Q000494:pharmacology; D023201:CD40 Ligand / Q000494:pharmacology; D016923:Cell Death; D002454:Cell Differentiation; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D015726:Giant Cells; D015658:HIV Infections / Q000097:blood / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology / Q000821:virology; D014774:Virulence; D014779:Virus Replication / Q000187:drug effects
D000906:Antibodies; D016898:Interferon-alpha; D023201:CD40 Ligand