Human cytomegalovirus latent infection of granulocyte-macrophage progenitors.

Abstract

We have investigated the interaction of human cytomegalovirus (CMV) with cultured primary granulo-

Anatomical mapping of human herpesvirus reservoirs of infection

“…[19][20][21][22][23][24][25][26][27][28][29][30][31] In contrast, congenital (in utero) infection leads to infection of the central nervous system. In the immunocompromised host, CMV lesions may be found in numerous organs, including lung, brain, liver, gastrointestinal tract, and kidney.…”

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.…”

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

“…We did not identify a significant difference in the timing or frequency of reactivation of viral IL-10 deletion virus in comparison to parental virus using our previously described reactivation assay, whereby latently infected cells were cocultured with monolayers of primary human foreskin fibroblasts to stimulate reactivation, and monolayers were monitored daily for the appearance of cytopathic effect (CPE) as an indicator of virus reactivation (8,9,22). Specifically, in four independent experiments, both parental virus and viral IL-10 deletion virus reactivated at the same time (mean time of 12 days after reactivation stimulus), and the frequencies of reactivation were very similar for the parental virus (1.2 ϫ 10 Ϫ4 ) and viral IL-10 deletion virus (1.3 ϫ 10 Ϫ4 ).…”

“…HCMV establishes and maintains a lifelong latent infection in primitive myeloid lineage cells (14,22,27,48,53,58). Following terminal cell differentiation of these cells into myeloid dendritic cells (DCs) and macrophages, latent virus has the ability to reactivate, resulting in the production of new, infectious virions and often severe disease in immunocompromised individuals (11,14,28,37,49,50,59,63).…”

“…To determine whether HCMV UL111A-encoded viral IL-10 affected expression of proinflammatory cytokines involved in modulating myeloid cell differentiation, we first evaluated mRNA expression of interleukin-1␤ (IL-1␤) and tumor necrosis factor alpha (TNF-␣) in cells latently infected with RVAdIL10C, a recombinant virus that cannot express any viral IL-10 (33), or its parent strain AD169. Primary human CD34 ϩ myeloid progenitors were latently infected as previously described (8,22), and cells and culture supernatants were harvested at day 8 postinfection (p.i.). We have previously demonstrated that this viral IL-10 deletion virus infects and maintains a latent infection in CD34 ϩ myeloid progenitors as efficiently as the parental virus does (9).…”