Human immunodeficiency virus viremia induces plasmacytoid dendritic cell activation in vivo and diminished alpha interferon production in vitro

John C. Tilton, Maura M. Manion, Marlise R. Luskin, Alison J. Johnson, Andy A. Patamawenu, Claire W. Hallahan, Nancy A. Cogliano-Shutta, Jo Ann M Mican, Richard T. Davey, Shyam Kottilil, Jeffrey D. Lifson, Julia A. Metcalf, Richard A. Lempicki, Mark Connors

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Human immunodeficiency virus type 1 (HIV-1) infection has been associated with perturbations of plasmacytoid dendritic cells (PDC), including diminished frequencies in the peripheral blood and reduced production of type I interferons (IFNs) in response to in vitro stimulation. However, recent data suggest a paradoxical increase in production of type 1 interferons in vivo in HIV-infected patients compared to uninfected controls. Using a flow cytometric assay to detect IFN-α-producing cells within unseparated peripheral blood mononuclear cells, we observed that short-term interruptions of antiretroviral therapy are sufficient to result in significantly reduced IFN-α production by PDC in vitro in response to CpG A ligands or inactivated HIV particles. The primary cause of diminished IFN-α production was reduced responsiveness of PDC to de novo stimulation, not diminished per cell IFN-α production or migration of cells to lymphoid organs. Real-time PCR analysis of purified PDC from patients prior to and during treatment interruptions revealed that active HIV-1 replication is associated with upregulation of type I IFN-stimulated gene expression. Treatment of hepatitis C virus-infected patients with IFN-α2b and ribavirin for hepatitis C virus infection resulted in a profound suppression of de novo IFN-α production in response to CpG A or inactivated HIV particles, similar to the response observed in HIV-infected patients. Together, these results suggest that diminished production of type I interferons in vitro by PDC from HIV-1-infected patients may not represent diminished interferon production in vivo. Rather, diminished function in vitro is likely a consequence of prior activation via type I interferons or HIV virions in vivo.

Original languageEnglish (US)
Pages (from-to)3997-4006
Number of pages10
JournalJournal of Virology
Volume82
Issue number8
DOIs
StatePublished - Apr 2008
Externally publishedYes

Fingerprint

interferon-alpha
Viremia
viremia
Human immunodeficiency virus
interferons
dendritic cells
Interferon-alpha
Dendritic Cells
Interferons
Interferon Type I
HIV
HIV-1
Virus Diseases
Hepacivirus
Human immunodeficiency virus 1
Hepatitis C virus
Ribavirin
Virus Replication
In Vitro Techniques
Virion

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Tilton, J. C., Manion, M. M., Luskin, M. R., Johnson, A. J., Patamawenu, A. A., Hallahan, C. W., ... Connors, M. (2008). Human immunodeficiency virus viremia induces plasmacytoid dendritic cell activation in vivo and diminished alpha interferon production in vitro. Journal of Virology, 82(8), 3997-4006. https://doi.org/10.1128/JVI.01545-07

Human immunodeficiency virus viremia induces plasmacytoid dendritic cell activation in vivo and diminished alpha interferon production in vitro. / Tilton, John C.; Manion, Maura M.; Luskin, Marlise R.; Johnson, Alison J.; Patamawenu, Andy A.; Hallahan, Claire W.; Cogliano-Shutta, Nancy A.; Mican, Jo Ann M; Davey, Richard T.; Kottilil, Shyam; Lifson, Jeffrey D.; Metcalf, Julia A.; Lempicki, Richard A.; Connors, Mark.

In: Journal of Virology, Vol. 82, No. 8, 04.2008, p. 3997-4006.

Research output: Contribution to journalArticle

Tilton, JC, Manion, MM, Luskin, MR, Johnson, AJ, Patamawenu, AA, Hallahan, CW, Cogliano-Shutta, NA, Mican, JAM, Davey, RT, Kottilil, S, Lifson, JD, Metcalf, JA, Lempicki, RA & Connors, M 2008, 'Human immunodeficiency virus viremia induces plasmacytoid dendritic cell activation in vivo and diminished alpha interferon production in vitro', Journal of Virology, vol. 82, no. 8, pp. 3997-4006. https://doi.org/10.1128/JVI.01545-07
Tilton, John C. ; Manion, Maura M. ; Luskin, Marlise R. ; Johnson, Alison J. ; Patamawenu, Andy A. ; Hallahan, Claire W. ; Cogliano-Shutta, Nancy A. ; Mican, Jo Ann M ; Davey, Richard T. ; Kottilil, Shyam ; Lifson, Jeffrey D. ; Metcalf, Julia A. ; Lempicki, Richard A. ; Connors, Mark. / Human immunodeficiency virus viremia induces plasmacytoid dendritic cell activation in vivo and diminished alpha interferon production in vitro. In: Journal of Virology. 2008 ; Vol. 82, No. 8. pp. 3997-4006.
@article{bc18bd4d747e40e6abd8bfc7fe71aaa6,
title = "Human immunodeficiency virus viremia induces plasmacytoid dendritic cell activation in vivo and diminished alpha interferon production in vitro",
abstract = "Human immunodeficiency virus type 1 (HIV-1) infection has been associated with perturbations of plasmacytoid dendritic cells (PDC), including diminished frequencies in the peripheral blood and reduced production of type I interferons (IFNs) in response to in vitro stimulation. However, recent data suggest a paradoxical increase in production of type 1 interferons in vivo in HIV-infected patients compared to uninfected controls. Using a flow cytometric assay to detect IFN-α-producing cells within unseparated peripheral blood mononuclear cells, we observed that short-term interruptions of antiretroviral therapy are sufficient to result in significantly reduced IFN-α production by PDC in vitro in response to CpG A ligands or inactivated HIV particles. The primary cause of diminished IFN-α production was reduced responsiveness of PDC to de novo stimulation, not diminished per cell IFN-α production or migration of cells to lymphoid organs. Real-time PCR analysis of purified PDC from patients prior to and during treatment interruptions revealed that active HIV-1 replication is associated with upregulation of type I IFN-stimulated gene expression. Treatment of hepatitis C virus-infected patients with IFN-α2b and ribavirin for hepatitis C virus infection resulted in a profound suppression of de novo IFN-α production in response to CpG A or inactivated HIV particles, similar to the response observed in HIV-infected patients. Together, these results suggest that diminished production of type I interferons in vitro by PDC from HIV-1-infected patients may not represent diminished interferon production in vivo. Rather, diminished function in vitro is likely a consequence of prior activation via type I interferons or HIV virions in vivo.",
author = "Tilton, {John C.} and Manion, {Maura M.} and Luskin, {Marlise R.} and Johnson, {Alison J.} and Patamawenu, {Andy A.} and Hallahan, {Claire W.} and Cogliano-Shutta, {Nancy A.} and Mican, {Jo Ann M} and Davey, {Richard T.} and Shyam Kottilil and Lifson, {Jeffrey D.} and Metcalf, {Julia A.} and Lempicki, {Richard A.} and Mark Connors",
year = "2008",
month = "4",
doi = "10.1128/JVI.01545-07",
language = "English (US)",
volume = "82",
pages = "3997--4006",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "8",

}

TY - JOUR

T1 - Human immunodeficiency virus viremia induces plasmacytoid dendritic cell activation in vivo and diminished alpha interferon production in vitro

AU - Tilton, John C.

AU - Manion, Maura M.

AU - Luskin, Marlise R.

AU - Johnson, Alison J.

AU - Patamawenu, Andy A.

AU - Hallahan, Claire W.

AU - Cogliano-Shutta, Nancy A.

AU - Mican, Jo Ann M

AU - Davey, Richard T.

AU - Kottilil, Shyam

AU - Lifson, Jeffrey D.

AU - Metcalf, Julia A.

AU - Lempicki, Richard A.

AU - Connors, Mark

PY - 2008/4

Y1 - 2008/4

N2 - Human immunodeficiency virus type 1 (HIV-1) infection has been associated with perturbations of plasmacytoid dendritic cells (PDC), including diminished frequencies in the peripheral blood and reduced production of type I interferons (IFNs) in response to in vitro stimulation. However, recent data suggest a paradoxical increase in production of type 1 interferons in vivo in HIV-infected patients compared to uninfected controls. Using a flow cytometric assay to detect IFN-α-producing cells within unseparated peripheral blood mononuclear cells, we observed that short-term interruptions of antiretroviral therapy are sufficient to result in significantly reduced IFN-α production by PDC in vitro in response to CpG A ligands or inactivated HIV particles. The primary cause of diminished IFN-α production was reduced responsiveness of PDC to de novo stimulation, not diminished per cell IFN-α production or migration of cells to lymphoid organs. Real-time PCR analysis of purified PDC from patients prior to and during treatment interruptions revealed that active HIV-1 replication is associated with upregulation of type I IFN-stimulated gene expression. Treatment of hepatitis C virus-infected patients with IFN-α2b and ribavirin for hepatitis C virus infection resulted in a profound suppression of de novo IFN-α production in response to CpG A or inactivated HIV particles, similar to the response observed in HIV-infected patients. Together, these results suggest that diminished production of type I interferons in vitro by PDC from HIV-1-infected patients may not represent diminished interferon production in vivo. Rather, diminished function in vitro is likely a consequence of prior activation via type I interferons or HIV virions in vivo.

AB - Human immunodeficiency virus type 1 (HIV-1) infection has been associated with perturbations of plasmacytoid dendritic cells (PDC), including diminished frequencies in the peripheral blood and reduced production of type I interferons (IFNs) in response to in vitro stimulation. However, recent data suggest a paradoxical increase in production of type 1 interferons in vivo in HIV-infected patients compared to uninfected controls. Using a flow cytometric assay to detect IFN-α-producing cells within unseparated peripheral blood mononuclear cells, we observed that short-term interruptions of antiretroviral therapy are sufficient to result in significantly reduced IFN-α production by PDC in vitro in response to CpG A ligands or inactivated HIV particles. The primary cause of diminished IFN-α production was reduced responsiveness of PDC to de novo stimulation, not diminished per cell IFN-α production or migration of cells to lymphoid organs. Real-time PCR analysis of purified PDC from patients prior to and during treatment interruptions revealed that active HIV-1 replication is associated with upregulation of type I IFN-stimulated gene expression. Treatment of hepatitis C virus-infected patients with IFN-α2b and ribavirin for hepatitis C virus infection resulted in a profound suppression of de novo IFN-α production in response to CpG A or inactivated HIV particles, similar to the response observed in HIV-infected patients. Together, these results suggest that diminished production of type I interferons in vitro by PDC from HIV-1-infected patients may not represent diminished interferon production in vivo. Rather, diminished function in vitro is likely a consequence of prior activation via type I interferons or HIV virions in vivo.

UR - http://www.scopus.com/inward/record.url?scp=41949103790&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41949103790&partnerID=8YFLogxK

U2 - 10.1128/JVI.01545-07

DO - 10.1128/JVI.01545-07

M3 - Article

C2 - 18256146

AN - SCOPUS:41949103790

VL - 82

SP - 3997

EP - 4006

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 8

ER -