Natural alpha interferon-producing cells respond to human immunodeficiency virus type 1 with alpha interferon production and maturation into dendritic cells

Akihito Yonezawa, Rimpei Morita, Akifumi Takaori-Kondo, Norimitsu Kadowaki, Toshio Kitawaki, Toshiyuki Hori, Takashi Uchiyama

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Natural alpha interferon (IFN-α)-producing cells (IPCs) are now recognized as identical to plasmacytoid dendritic cell (DC) precursors in human blood and are thought to play an important role in antiviral immunity. In the present study, we examined the susceptibility as well as the cellular responses of IPCs to human immunodeficiency virus type 1 (HIV-1) infection. HLA-DR+ CD11c- lineage-negative cells (IPCs) were purified from peripheral blood mononuclear cells by magnetic-bead separation and cell sorting. We substantiated that IPCs expressing the major HIV-1 coreceptors, CXCR4 and CCR5, are susceptible to infection of both T-cell-line-tropic NL4-3 and macrophage-tropic JR-CSF HIV-1 by quantification of HIV-1 p24 in the culture supernatants and by provirus integration assay using human conserved Alu-HIV-1 long terminal repeat PCR. To evaluate the cellular response of IPCs to HIV-1, we examined IFN-α production and their differentiation into DCs. After incubation with either NL4-3 or JR-CSF, IPCs produced a large amount of IFN-α and at the same time underwent morphological differentiation into DCs with upregulation of CD80 and CD86. Heat inactivation of the supernatants containing HIV-1 did not affect the IFN-α production and maturation, whereas removal of virions by ultracentrifugation completely nullified both biological effects, indicating that these cellular responses do not require actual HIV-1 infection but are elicited by interaction with HIV-1 virions or certain viral components. In conclusion, these data strongly suggest that IPC can directly recognize and respond to HIV-1 with IFN-α production, which is crucial for preventing progress of HIV-1 infection and occurrence of opportunistic infection.

Original languageEnglish
Pages (from-to)3777-3784
Number of pages8
JournalJournal of Virology
Volume77
Issue number6
DOIs
Publication statusPublished - 2003 Mar
Externally publishedYes

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interferon-alpha
dendritic cells
Human immunodeficiency virus 1
Interferon-alpha
Dendritic Cells
HIV-1
interferons
Virus Diseases
cells
Interferon Type I
Virion
Interferons
virion
infection
HIV Long Terminal Repeat
HIV
Virus Integration
tropics
Viral Structures
Cell Separation

ASJC Scopus subject areas

  • Immunology

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Natural alpha interferon-producing cells respond to human immunodeficiency virus type 1 with alpha interferon production and maturation into dendritic cells. / Yonezawa, Akihito; Morita, Rimpei; Takaori-Kondo, Akifumi; Kadowaki, Norimitsu; Kitawaki, Toshio; Hori, Toshiyuki; Uchiyama, Takashi.

In: Journal of Virology, Vol. 77, No. 6, 03.2003, p. 3777-3784.

Research output: Contribution to journalArticle

Yonezawa, Akihito ; Morita, Rimpei ; Takaori-Kondo, Akifumi ; Kadowaki, Norimitsu ; Kitawaki, Toshio ; Hori, Toshiyuki ; Uchiyama, Takashi. / Natural alpha interferon-producing cells respond to human immunodeficiency virus type 1 with alpha interferon production and maturation into dendritic cells. In: Journal of Virology. 2003 ; Vol. 77, No. 6. pp. 3777-3784.
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