Reactivation of latent human cytomegalovirus in CD14+ monocytes is differentiation dependent

C. Söderberg-Nauclér, Daniel Streblow, K. N. Fish, J. Allan-Yorke, P. P. Smith, Jay Nelson

Research output: Contribution to journalArticle

164 Citations (Scopus)

Abstract

We have previously demonstrated reactivation of latent human cytomegalovirus (HCMV) in myeloid lineage cells obtained from healthy donors. Virus was obtained from allogenically stimulated monocyte-derived macrophages (Allo-MDM), but not from macrophages differentiated by mitogenic stimulation (ConA-MDM). In the present study, the cellular and cytokine components essential for HCMV replication and reactivation were examined in Allo-MDM. The importance of both CD4+ and CD8+ T cells in the generation of HCMV-permissive Allo-MDM was demonstrated by negative selection or blocking experiments using antibodies directed against both HLA class I and HLA class II molecules. Interestingly, contact of monocytes with CD4 or CD8 T cells was not essential for reactivation of HCMV, since virus was observed in macrophages derived from CD14+ monocytes stimulated by supernatants produced by allogeneic stimulation of peripheral blood mononuclear cells. Examination of the cytokines produced in Allo-MDM and ConA-MDM cultures indicated a significant difference in the kinetics of production and quantity of these factors. Further examination of the cytokines essential for the generation of HCMV-permissive Allo-MDM identified gamma interferon (IFN-γ) but not interleukin-1 or -2, tumor necrosis factor alpha, or granulocyte-macrophage colony-stimulating factor as critical components in the generation of these macrophages. In addition, although IFN-γ was crucial for reactivation of latent HCMV, addition of IFN-γ to unstimulated macrophage cultures was insufficient to reactivate virus. Thus, this study characterizes two distinct monocyte-derived cell types which can be distinguished by their ability to reactivate and support HCMV replication and identifies the critical importance of IFN-γ in the reactivation of HCMV.

Original languageEnglish (US)
Pages (from-to)7543-7554
Number of pages12
JournalJournal of Virology
Volume75
Issue number16
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Human herpesvirus 5
Cytomegalovirus
monocytes
Monocytes
macrophages
Macrophages
cytokines
Cytokines
Viruses
viruses
T-lymphocytes
T-Lymphocytes
granulocyte-macrophage colony-stimulating factor
interleukin-1
Myeloid Cells
Granulocyte-Macrophage Colony-Stimulating Factor
mononuclear leukocytes
interferon-gamma
Interleukin-1
tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Immunology

Cite this

Reactivation of latent human cytomegalovirus in CD14+ monocytes is differentiation dependent. / Söderberg-Nauclér, C.; Streblow, Daniel; Fish, K. N.; Allan-Yorke, J.; Smith, P. P.; Nelson, Jay.

In: Journal of Virology, Vol. 75, No. 16, 2001, p. 7543-7554.

Research output: Contribution to journalArticle

Söderberg-Nauclér, C. ; Streblow, Daniel ; Fish, K. N. ; Allan-Yorke, J. ; Smith, P. P. ; Nelson, Jay. / Reactivation of latent human cytomegalovirus in CD14+ monocytes is differentiation dependent. In: Journal of Virology. 2001 ; Vol. 75, No. 16. pp. 7543-7554.
@article{f282d97e2da144d692aa5ff3e065a3cb,
title = "Reactivation of latent human cytomegalovirus in CD14+ monocytes is differentiation dependent",
abstract = "We have previously demonstrated reactivation of latent human cytomegalovirus (HCMV) in myeloid lineage cells obtained from healthy donors. Virus was obtained from allogenically stimulated monocyte-derived macrophages (Allo-MDM), but not from macrophages differentiated by mitogenic stimulation (ConA-MDM). In the present study, the cellular and cytokine components essential for HCMV replication and reactivation were examined in Allo-MDM. The importance of both CD4+ and CD8+ T cells in the generation of HCMV-permissive Allo-MDM was demonstrated by negative selection or blocking experiments using antibodies directed against both HLA class I and HLA class II molecules. Interestingly, contact of monocytes with CD4 or CD8 T cells was not essential for reactivation of HCMV, since virus was observed in macrophages derived from CD14+ monocytes stimulated by supernatants produced by allogeneic stimulation of peripheral blood mononuclear cells. Examination of the cytokines produced in Allo-MDM and ConA-MDM cultures indicated a significant difference in the kinetics of production and quantity of these factors. Further examination of the cytokines essential for the generation of HCMV-permissive Allo-MDM identified gamma interferon (IFN-γ) but not interleukin-1 or -2, tumor necrosis factor alpha, or granulocyte-macrophage colony-stimulating factor as critical components in the generation of these macrophages. In addition, although IFN-γ was crucial for reactivation of latent HCMV, addition of IFN-γ to unstimulated macrophage cultures was insufficient to reactivate virus. Thus, this study characterizes two distinct monocyte-derived cell types which can be distinguished by their ability to reactivate and support HCMV replication and identifies the critical importance of IFN-γ in the reactivation of HCMV.",
author = "C. S{\"o}derberg-Naucl{\'e}r and Daniel Streblow and Fish, {K. N.} and J. Allan-Yorke and Smith, {P. P.} and Jay Nelson",
year = "2001",
doi = "10.1128/JVI.75.16.7543-7554.2001",
language = "English (US)",
volume = "75",
pages = "7543--7554",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "16",

}

TY - JOUR

T1 - Reactivation of latent human cytomegalovirus in CD14+ monocytes is differentiation dependent

AU - Söderberg-Nauclér, C.

AU - Streblow, Daniel

AU - Fish, K. N.

AU - Allan-Yorke, J.

AU - Smith, P. P.

AU - Nelson, Jay

PY - 2001

Y1 - 2001

N2 - We have previously demonstrated reactivation of latent human cytomegalovirus (HCMV) in myeloid lineage cells obtained from healthy donors. Virus was obtained from allogenically stimulated monocyte-derived macrophages (Allo-MDM), but not from macrophages differentiated by mitogenic stimulation (ConA-MDM). In the present study, the cellular and cytokine components essential for HCMV replication and reactivation were examined in Allo-MDM. The importance of both CD4+ and CD8+ T cells in the generation of HCMV-permissive Allo-MDM was demonstrated by negative selection or blocking experiments using antibodies directed against both HLA class I and HLA class II molecules. Interestingly, contact of monocytes with CD4 or CD8 T cells was not essential for reactivation of HCMV, since virus was observed in macrophages derived from CD14+ monocytes stimulated by supernatants produced by allogeneic stimulation of peripheral blood mononuclear cells. Examination of the cytokines produced in Allo-MDM and ConA-MDM cultures indicated a significant difference in the kinetics of production and quantity of these factors. Further examination of the cytokines essential for the generation of HCMV-permissive Allo-MDM identified gamma interferon (IFN-γ) but not interleukin-1 or -2, tumor necrosis factor alpha, or granulocyte-macrophage colony-stimulating factor as critical components in the generation of these macrophages. In addition, although IFN-γ was crucial for reactivation of latent HCMV, addition of IFN-γ to unstimulated macrophage cultures was insufficient to reactivate virus. Thus, this study characterizes two distinct monocyte-derived cell types which can be distinguished by their ability to reactivate and support HCMV replication and identifies the critical importance of IFN-γ in the reactivation of HCMV.

AB - We have previously demonstrated reactivation of latent human cytomegalovirus (HCMV) in myeloid lineage cells obtained from healthy donors. Virus was obtained from allogenically stimulated monocyte-derived macrophages (Allo-MDM), but not from macrophages differentiated by mitogenic stimulation (ConA-MDM). In the present study, the cellular and cytokine components essential for HCMV replication and reactivation were examined in Allo-MDM. The importance of both CD4+ and CD8+ T cells in the generation of HCMV-permissive Allo-MDM was demonstrated by negative selection or blocking experiments using antibodies directed against both HLA class I and HLA class II molecules. Interestingly, contact of monocytes with CD4 or CD8 T cells was not essential for reactivation of HCMV, since virus was observed in macrophages derived from CD14+ monocytes stimulated by supernatants produced by allogeneic stimulation of peripheral blood mononuclear cells. Examination of the cytokines produced in Allo-MDM and ConA-MDM cultures indicated a significant difference in the kinetics of production and quantity of these factors. Further examination of the cytokines essential for the generation of HCMV-permissive Allo-MDM identified gamma interferon (IFN-γ) but not interleukin-1 or -2, tumor necrosis factor alpha, or granulocyte-macrophage colony-stimulating factor as critical components in the generation of these macrophages. In addition, although IFN-γ was crucial for reactivation of latent HCMV, addition of IFN-γ to unstimulated macrophage cultures was insufficient to reactivate virus. Thus, this study characterizes two distinct monocyte-derived cell types which can be distinguished by their ability to reactivate and support HCMV replication and identifies the critical importance of IFN-γ in the reactivation of HCMV.

UR - http://www.scopus.com/inward/record.url?scp=0034899174&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034899174&partnerID=8YFLogxK

U2 - 10.1128/JVI.75.16.7543-7554.2001

DO - 10.1128/JVI.75.16.7543-7554.2001

M3 - Article

VL - 75

SP - 7543

EP - 7554

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 16

ER -