Human Cytomegalovirus Induces Monocyte Differentiation and Migration as a Strategy for Dissemination and Persistence

2004/04/12 by M. Shane Smith, Gretchen L. Bentz, J. Steven Alexander +1 · 249 citations
Immunology and Microbiology · Medicine · #Biology #Cell #Cell type #Cytomegalovirus #Cytomegalovirus and herpesvirus research #Genetics #Herpesviridae #Herpesvirus Infections and Treatments #Human cytomegalovirus #Immunology #In vitro #Macrophage #Monocyte #Pathogenesis #Toxoplasma gondii Research Studies #Viral disease #Viral replication #Viremia #Virology #Virus

paper · open access · doi:10.1128/jvi.78.9.4444-4453.2004

published in Journal of Virology 78(9), 4444-4453 (American Society for Microbiology)

openalex publication_date 2004/04/12 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

Abstract

Human cytomegalovirus (HCMV) pathogenesis is characterized by multiple organ system involvement due to viral spread to host organs after a cell-associated viremia. The cell type responsible for HCMV dissemination is unknown. Monocytes are the most likely candidate since they are the predominant cell type infected in the blood. However, monocytes are not productive for viral replication and are abortively infected. The results presented here provide a potential answer to this conundrum. We report that primary HCMV infection of monocytes induces transendothelial migration and monocyte-to-macrophage differentiation and that these HCMV-differentiated macrophages are productive for viral replication. Together, our data suggest a novel mechanism for HCMV pathogenesis; HCMV induces cellular changes in monocytes to promote viral replication and spread to host organs.

Citations

• Induction of endogenous human cytomegalovirus gene expression after differentiation of monocytes from healthy carriers
• Macrosialin, a macrophage-restricted membrane sialoprotein differentially glycosylated in response to inflammatory stimuli.

Cited by

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• Human Cytomegalovirus Glycoprotein-Initiated Signaling Mediates the Aberrant Activation of Akt
• CD34+Hematopoietic Progenitor Cell Subsets Exhibit Differential Ability To Maintain Human Cytomegalovirus Latency and Persistence
• Human cytomegalovirus modulates mTORC1 to redirect mRNA translation within quiescently infected monocytes
• Human cytomegalovirus-triggered necroptosis is suppressed by sequestration of MLKL in the nucleus of infected monocytes
• Cytomegalovirus latency—the sum of subtleties
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• M1/M2 macrophages and their overlaps – myth or reality?
• NF-κB and phosphatidylinositol 3-kinase activity mediates the HCMV-induced atypical M1/M2 polarization of monocytes
• Activation of human monocytes after infection by human coronavirus 229E. [europepmc]
• Human CMV infection of endothelial cells induces an angiogenic response through viral binding to EGF receptor and beta1 and beta3 integrins. [europepmc]
• Transcriptome analysis reveals human cytomegalovirus reprograms monocyte differentiation toward an M1 macrophage. [europepmc]
• NF-kappaB and phosphatidylinositol 3-kinase activity mediates the HCMV-induced atypical M1/M2 polarization of monocytes. [europepmc]
• PI3K-dependent upregulation of Mcl-1 by human cytomegalovirus is mediated by epidermal growth factor receptor and inhibits apoptosis in short-lived monocytes. [europepmc]
• Granulocyte-colony stimulating factor reactivates human cytomegalovirus in a latently infected humanized mouse model. [europepmc]
• Human cytomegalovirus-regulated paxillin in monocytes links cellular pathogenic motility to the process of viral entry. [europepmc]
• Orientia tsutsugamushi stimulates an original gene expression program in monocytes: relationship with gene expression in patients with scrub typhus. [europepmc]
• The HCMV gH/gL/UL128-131 complex triggers the specific cellular activation required for efficient viral internalization into target monocytes. [europepmc]
• HCMV reprogramming of infected monocyte survival and differentiation: a Goldilocks phenomenon. [europepmc]
• Human Cytomegalovirus US28 Is Important for Latent Infection of Hematopoietic Progenitor Cells. [europepmc]
• Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells. [europepmc]
• Human Cytomegalovirus miR-UL148D Facilitates Latent Viral Infection by Targeting Host Cell Immediate Early Response Gene 5. [europepmc]
• Human Cytomegalovirus Requires Epidermal Growth Factor Receptor Signaling To Enter and Initiate the Early Steps in the Establishment of Latency in CD34 + Human Progenitor Cells. [europepmc]
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• Human Cytomegalovirus Tropism Modulator UL148 Interacts with SEL1L, a Cellular Factor That Governs Endoplasmic Reticulum-Associated Degradation of the Viral Envelope Glycoprotein gO. [europepmc]
• Molecular Determinants and the Regulation of Human Cytomegalovirus Latency and Reactivation. [europepmc]
• STING induces early IFN-β in the liver and constrains myeloid cell-mediated dissemination of murine cytomegalovirus. [europepmc]
• Interferon-Independent Innate Responses to Cytomegalovirus. [europepmc]
• Single cell analysis reveals human cytomegalovirus drives latently infected cells towards an anergic-like monocyte state. [europepmc]
• Cytomegalovirus Latency and Reactivation: An Intricate Interplay With the Host Immune Response. [europepmc]
• Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19. [europepmc]
• Regulation of the MIE Locus During HCMV Latency and Reactivation. [europepmc]
• Monocytes and Macrophages in COVID-19. [europepmc]
• M1/M2 macrophages and their overlaps - myth or reality? [europepmc]

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