Human cytomegalovirus persists in myeloid progenitors and is passed to the myeloid progeny in a latent form

Abstract

Summary CD34+ progenitor cells can harbour latent human cytomegalovirus (HCMV); however, the mechanisms of HCMV latency remain unclear. We have investigated the effects of the haematopoietic lineage restriction on the establishment and spread of the latent HCMV to progeny cells. In vitro‐infected and latently‐infected haematopoietic progenitor cells derived from HCMV seropositive donors were studied. The presence of HCMV DNA in bone marrow progenitor (BMP) cells was determined by single colony polymerase chain reaction and fluorescent in situ hybridization (FISH). The presence of CMV DNA was found to be restricted to myeloid progenitors and the percentage of HCMV‐infected cells was lower in naturally‐infected cells than in in vitro‐infected cells. Erythroid differentiation resulted in an abortive infection with persistence of the viral nucleic acids in red cell precursors. In BMP cells from HCMV seronegative donors, HCMV DNA was localized in the nucleus. Bone marrow progenitors in the presence of granulocyte‐macrophage colony stimulating factor (GMCSF) maintained HCMV DNA for extended periods of time. No viral production could be detected throughout the culture but the comparison of the numbers of latently‐infected cells prior to and after the culture suggests that proliferation of haematopoietic progenitor cells may lead to the expansion of latently‐infected cells.

Anatomical mapping of human herpesvirus reservoirs of infection

“…Sites of CMV latency have been clearly established but may include marrow myeloid progenitors, spleen, arterial smooth muscle, and bronchoalveolar cells. [32][33][34][35][36] CMV DNA has also been detected in a wide variety of other cell types including hepatocytes, renal tubular and glomerular cells, splenic red pulp cells, and pancreatic acinar cells from healthy adults. 37 In the present study, CMV was detected in three of eight cases within nasopulmonary tissues (nasal mucosa, trachea, lung), thyroid gland, small and large intestine, anus, urinary tissues (urethra, urinary bladder), and lymph node.…”

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

“…67 Thus, it may be difficult to identify coinfected cells in natural specimens, especially in normal PB. It is postulated that nondetectable HCMV reactivation and replication can lead to new infections in other cell types and in turn repopulate the latent viral genome in CD34 1 cells.…”

Lack of presence of the human cytomegalovirus in human glioblastoma

“…26 One reason for this discrepancy may be because extremely small amount of DNA can be detected by traditional PCR techniques that were utilized such as nested-PCR utilized in the previous study 1 in which 35-50 cycles of amplification followed by a second round of amplification, and HCMV DNA from cells other than the tumor cells were detected. Glioblastoma is often accompanied with reactive gliosis at the edge of the tumor tissue, and microglial cells that originate from bone marrow myeloid cells, which may be persistently infected by HCMV, 27 could have important roles in the development of gliosis. 28 Thus, we consider that these positive PCR results different from ours may be because of relatively smaller content of reactive glial cells in our samples.…”