Control of Cytokines in Latent Cytomegalovirus Infection

Abstract

Human cytomegalovirus (HCMV) has evolved a number of mechanisms for long-term co-existence within its host. HCMV infects a wide range of cell types, including fibroblasts, epithelial cells, monocytes, macrophages, dendritic cells, and myeloid progenitor cells. Lytic infection, with the production of infectious progeny virions, occurs in differentiated cell types, while undifferentiated myeloid precursor cells are the primary site of latent infection. The outcome of HCMV infection depends partly on the cell type and differentiation state but is also influenced by the composition of the immune environment. In this review, we discuss the role of early interactions between HCMV and the host immune system, particularly cytokine and chemokine networks, that facilitate the establishment of lifelong latent infection. A better understanding of these cytokine signaling pathways could lead to novel therapeutic targets that might prevent latency or eradicate latently infected cells.

Cytomegalovirus viremia is associated with poor outcomes in AIDS patients with disseminated nontuberculous mycobacterial disease

“…Viral infections can increase the production of Type 1 interferons (e.g., interferon-alpha), which may subsequently impair Th1 cytokine (e.g., interferon-gamma) responses (18).Thus, a concomitant infection with CMV could potentially counteract protective Th1 immune responses to a mycobacterial infection (19). The stimulation of peripheral blood mononuclear cells with CMV antigens results in lower levels of interferon-gamma and tumor necrosis factor alpha in CMV-seropositive versus CMV-seronegative patients (20).…”

Human cytomegalovirus blocks canonical TGFβ signaling during lytic infection to limit induction of type I interferons

“…To evade the innate immune response, HCMV encodes numerous gene products that block the induction of intrinsic antiviral responses and the production of IFN and IFN stimulated genes (ISGs) (reviewed in [ 2 , 3 ]). Along with IFNs, viral infection results in the secretion of additional cellular and viral cytokines and chemokines, which act in an autocrine and paracrine fashion to alter the intracellular and extracellular environment [ 4 ]. For example, lytically infected cells [ 5 – 7 ] as well as latently-infected CD34 + hematopoietic progenitor cells (HPCs) [ 8 – 10 ], produce and secrete transforming growth factor beta (TGFβ) which causes myelosuppression and has significant implications for hematopoietic stem cell transplantation [ 9 ].…”

Human cytomegalovirus blocks canonical TGFβ signaling during lytic infection to limit induction of type I interferons

“…To evade the innate immune response, HCMV encodes numerous gene products that block the induction of intrinsic antiviral responses and the production of IFN and IFN stimulated genes (ISGs) (reviewed in (2, 3)). Along with IFNs, viral infection results in the secretion of additional cellular and viral cytokines and chemokines, which act in an autocrine and paracrine fashion to alter the intracellular and extracellular environment (4). For example, lytically infected cells (5-7) as well as latently-infected CD34 + hematopoietic progenitor cells (HPCs) (8-10), produce and secrete TGFβ which causes myelosuppression and has significant implications for hematopoietic stem cell transplantation (9).…”

“…[2][3][4][5][6][7][8], and most commonly the 3' UTR of the targeted gene, although binding to other regions of the transcript can also mediate regulation(20). miRNAs are the mRNA recognition component of a larger multi-protein RNA-induced silencing…”