Definition of a subset of human peripheral blood mononuclear cells that are permissive to human cytomegalovirus infection

Abstract

The identity of cells responsible for transmission of human cytomegalovirus (HCMV) in blood products or bone marrow transplants is unknown. We have tested the capacity of HCMV to in vitro infect human peripheral blood mononuclear cells (PBMC) from healthy donors and found that certain PBMC are permissive to HCMV infection. In vitro-infected viable cells were double stained for surface expression of different HMCV proteins and for cell-type-specific antigens to allow the identification of sensitive cells. All analysis were performed on viable cells, using HCMV-specific monoclonal antibodies and automated flow cytofluorimetry. PBMC were infected either with the laboratory-adapted HCMV strain AD169 or with a virus isolate obtained from a viremic patient. Up to 25% of all PBMC could express the major immediate-early antigen as well as the pp65 antigen, known as the lower matrix protein. Infected cells were mainly CD14+ monocytes, but also a small population of large CD8+ cells were susceptible to HCMV infection. CD19+ B lymphocytes were resistant to HCMV infection. Different populations of infected cells were enriched by using Dynabeads coated with cell-type-specific antibodies, and the presence of infectious virus was demonstrated by incubating the selected and sonicated cell material on human fibroblasts. Only material from infected monocytes and from CD3+ CD8+ cells gave rise to HCMV-specific plaques. The presence of HCMV mRNA as a sign of active viral transcription of the major immediate-early and late ppl50 genes in infected cells was demonstrated by using nested reversed polymerase chain reaction. A common denominator was found for all cells that could be infected with HCMV. The CD13 antigen, a 130to 150-kDa integral membrane protein identical to the enzyme aminopeptidase N, was expressed on all HCMV-permissive cells.

Human cytomegalovirus suppresses type I interferon secretion by plasmacytoid dendritic cells through its interleukin 10 homolog

“…At 48 h post infection, FACS analysis was conducted to determine the frequency of the infected cells and their identity. The predominant HCVM-infected cell population was the CD14 + monocyte (data not shown), consistent with a previous report (Soderberg et al, 1993). In addition, a small fraction of non-B non-T cells also became EGFP + , suggesting that these cells either were infected by HCMV or engulfed cell components of other infected cells (data not shown).…”

Peptidases in human bronchoalveolar lining fluid, macrophages, and epithelial cells: Dipeptidyl (amino)peptidase IV, aminopeptidase N, and dipeptidyl (carboxy)peptidase (angiotensin-converting enzyme)

“…3° CD13-positive cells are permissive for cytomegalovirus infection. 31 Human APN has been shown to be a receptor for two human corona viruses from the gastrointestinal tract and human lung fibroblasts. 32 '33 In BAL fluid, we show that soluble APN activity was linked to an increased proportion of polymorphonuclear cells.…”

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

“…It is believed that PBM acquire HCMV during primary infection (Taylor-Wiedeman et al, 1991). The susceptibility of PBM to HCMV infection has been demonstrated in vitro (Rice et al, 1984;Scott et al, 1989;Rubin, 1990;Söderberg et al, 1993) and in vivo (Danker et al, 1990;Slobedman & Mocarski, 1999). Latently-infected haematopoietic cells may be a source of the HCMV reactivation that occurs in immunodeficient patients (St Jeor & Weisser, 1977;Rice et al, 1984;Drew, 1988;Danker et al, 1990).…”