Viral Interleukin-10 Expressed by Human Cytomegalovirus during the Latent Phase of Infection Modulates Latently Infected Myeloid Cell Differentiation

Abstract

The human cytomegalovirus UL111A gene is expressed during latent and productive infections, and it codes for homologs of interleukin-10 (IL-10). We examined whether viral IL-10 expressed during latency altered differentiation of latently infected myeloid progenitors. In comparison to infection with parental virus or mock infection, latent infection with a virus in which the gene encoding viral IL-10 has been deleted upregulated cytokines associated with dendritic cell (DC) formation and increased the proportion of myeloid DCs. These data demonstrate that viral IL-10 restricts the ability of latently infected myeloid progenitors to differentiate into DCs and identifies an immunomodulatory role for viral IL-10 which may limit the host's ability to clear latent virus.

Mechanisms modulating immune clearance during human cytomegalovirus latency

“…This report (3) also highlights the role of human (h)IL-10, which adds to previous studies that focused on virus-encoded IL-10 expressed during latency (17,(22)(23)(24). On the one hand, viral IL-10 may induce hIL-10.…”

The immunology of human cytomegalovirus latency: could latent infection be cleared by novel immunotherapeutic strategies?

“…28 Consistent with cells of the myeloid lineage being sites of latent infection, analyses of the viral transcription programme in these cells generally shows a suppression of viral lytic gene expression 2,29-32 but concomitant expression of known latency-associated viral genes. 31,[33][34][35][36][37] Importantly, these cells do not produce infectious virions; an essential characteristic of latent infection. In latent myeloid cells in vivo, this suppression of the lytic transcription programme appears to involve repression of the viral major immediate early promoter (MIEP), which would normally drive lytic cycle, through post-translational modification of histones around the MIEP resulting in the presence of well characterized repressive chromatin marks (reviewed in Ref.…”

Latent human cytomegalovirus enhances HIV-1 infection in CD34+ progenitor cells

“…Thus, HCMV can establish latent infection in PB-CD34 cells and appears to modulate immune molecules. 42,44 HCMV latently infected PB-CD34 cells are more susceptible to HIV-1 infection Because AIDS progresses faster in HCMV-seropositive individuals, we next examined if latently infected PB-CD34 cells can favor HIV-1 infection. HCMV or mock infection of PB-CD34 cells at day 5 PI were infected by HIV-1 NL4-3 (X4-tropic; X4-HIV).…”

“…HCMV latent infection could modulate human fetal liver-derived CD34 1 cell immune molecules 4,42 ; therefore, we examined cell surface expression of HLA-DR, MHC class I, CD80, CD83, and CD86 by flow cytometry following mock-or Merlin-infected PB-CD34 cells. Consistent to previous reports, 4,43 HLA-DR expression was downmodulated to the level of uninfected cells (supplemental Figure 3), whereas MHC class I molecules and the costimulatory molecules CD80 and CD83 (but not CD86) were significantly upregulated (supplemental Figure 3).…”