Monocytes are a major site of persistence of human cytomegalovirus in peripheral blood mononuclear cells

Abstract

We have used the nested polymerase chain reaction (PCR) combined with fluorescence-activated cell sorting to define sites of latency of human cytomegalovirus (HCMV) in the peripheral blood of healthy subjects. Peripheral blood mononuclear (PBM) cells were separated into T cell or non-T cell populations and monocytes, and were then analysed by PCR for the presence of HCMV DNA. In five of six seropositive subjects, HCMV was found predominantly in the non-T cell population. Further analysis suggested that the virus was present in adherent cells and CD 14 + cells. In three of nine seronegative subjects we could demonstrate HCMV DNA, which we do not believe was due to contamination, reproducibly by PCR. In one of these seronegative subjects, HCMV DNA was present predominantly in the non-T cell fraction of PBM cells. No HCMV DNA was detectable in the remaining six seronegative subjects. We conclude that, within the PBM cells of normal asymptomatic seropositive and some seronegative subjects, HCMV is present predominantly in the monocyte fraction. In addition, the detection of HCMV sequences in seronegative subjects may indicate that infection with HCMV is more widespread than conventional seroepidemiology suggests.

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?

“…26,27 Intriguingly, although CD34 1 bone marrow progenitor cells are also the source of cells of the lymphoid lineage, there is no evidence of viral genome carriage in peripheral blood B or T cells. 25 This may in part be explained by recent evidence suggesting that latent infection itself may result in some partial commitment of CD34 1 progenitors to the myeloid lineage. 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.…”

“…Latent viral genomes can be detected in peripheral monocytes 25 and also traced back to their CD34 1 progenitors in the bone marrow. 26,27 Intriguingly, although CD34 1 bone marrow progenitor cells are also the source of cells of the lymphoid lineage, there is no evidence of viral genome carriage in peripheral blood B or T cells.…”

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

“…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).…”