Immunobiology of Infection with Human Cytomegalovirus

Kirchner, Holger

doi:10.1016/s0065-230x(08)60679-x

Cited by 25 publications

(12 citation statements)

References 248 publications

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“…Human cytomegalovirus (HCMV) has been frequently isolated from human leukocytes and their subsets as reported from different laboratories throughout the last 10 years (Harnden et al, 1967;Fiala et at., 1975;Rinaldo et aL, 1977;Macher et al, 1983; summarized by Kirchner, 1983). Positive results of virus isolation were most frequently achieved by co-cultivation of human granulocytes with indicator cells, suggesting that the granulocyte cell fraction is one of the major virus reservoirs (Fiala et al, 1975 ;Rinaldo et aL, 1980).…”

Section: Introductionmentioning

confidence: 99%

Human Cytomegalovirus Replicates in Primary Human Bone Marrow Cells

Reiser

Kühn

Doerr

et al. 1986

Journal of General Virology

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SUMMARYAS an attempt to elucidate further the pathogenesis of human cytomegalovirus (HCMV) infection the replication of HCMV in primary human bone marrow cells (BMC) has been investigated. It was found that BMC held in culture in general were susceptible to HCMV infection. Compared to human embryonic lung cells, however, the replicative cycle of HCMV AD169 in BMC as determined by the analysis of viral protein and DNA synthesis was delayed and productive virus infection was restricted to a subset of BMC not exceeding 21% of the total cell population. Both of these phenomena may explain the short-term persistence of HCMV in BMC cultures which was observed over 3 months. By experiments with specifically enriched and depleted cell populations and by indirect double immunofluorescence experiments we found that both bone marrow fibroblasts and a subset of bone marrow stem cells supported productive virus infection. The finding that HCMV replicates in early stem cells of the human bone marrow may explain important aspects of the pathogenesis of HCMV infection including the presence of HCMV in peripheral blood leukocytes. INTRODUCTIONHuman cytomegalovirus (HCMV) has been frequently isolated from human leukocytes and their subsets as reported from different laboratories throughout the last 10 years (Harnden et al., 1967;Fiala et at., 1975;Rinaldo et aL, 1977;Macher et al., 1983; summarized by Kirchner, 1983). Positive results of virus isolation were most frequently achieved by co-cultivation of human granulocytes with indicator cells, suggesting that the granulocyte cell fraction is one of the major virus reservoirs (Fiala et al., 1975 ;Rinaldo et aL, 1980). Attempts to cultivate HCMV in vitro in primary human polymorphonuclear or mononuclear cells, however, were not successful and even infection of progenitor cell lines such as myeloblastoid lines did not lead to any appreciable virus replication (Rinaldo et al., 1978 ; Einhorn & Ost, 1984), The recent finding of HCMV RNA in lymphocytes of naturally infected individuals (Schrier et al., 1985) would suggest the possibility that HCMV does replicate in lymphocytes in vivo. These results, however, would not exclude the possibility that virus replication can also occur in early stem cells of the human bone marrow (Hirsch, 1984). The latter theory is supported by the finding that HCMV patients frequently show alterations of bone marrow cells (BMC) especially thrombocytopenia (Verdonck et al., 1985), and that in generalized infections the presence of HCMV can be demonstrated in the bone marrow (Brunning, 1981 ;Bodem et al., 1983). Furthermore, HCMV infection is the most frequent disease observed after bone marrow transplantation (Neimann et al., 1977) and the reported T cell subset alterations after HCMV infection (Carney et al., 1981) may well be explained by replication of the virus in early stem cells. Moreover, several reports on the replication of HCMV in different erythroleukaemic and lymphoblastoid cell lines in vitro suggest a susceptibility to HCMV of immature cells ...

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Section: Introductionmentioning

confidence: 99%

Human Cytomegalovirus Replicates in Primary Human Bone Marrow Cells

Reiser

Kühn

Doerr

et al. 1986

Journal of General Virology

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“…It has been emphasized that HCMV reactivation in vivo is due to the interaction of histoincompatible cells in patients who have been given transfusions or transplants (22), and Olding et al (28) showed that cytomegalovirus may be activated from murine lymphocytes by allogeneic reaction. This prompted us to investigate the comparative replication of HCMV in different human leukocyte subpopulations with special regard to T lymphocytes stimulated in the allogeneic mixed lymphocyte culture (MLC) and grown in the presence of IL-2.…”

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confidence: 99%

Replication of human cytomegalovirus in human peripheral blood T cells

Braun¹,

Reiser²

1986

J Virol

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The replication of human cytomegalovirus (HCMV) strain AD169 was studied in human peripheral blood granulocytes, monocytes-macrophages, B lymphocytes, and T lymphocytes. Progeny virus was produced in some T-cell cultures stimulated in the allogeneic mixed lymphocyte reaction and was regularly obtained when stimulated T cells were grown in the presence of interleukin 2. Replication of HCMV in these cultures was documented by increases in titer, expression of early and late antigen as assessed by indirect immunofluorescence and Western blot, and viral DNA synthesis as determined by dot-blot assays. Approximately 0.05% of cells in virus-producing cultures formed infectious centers, indicating that only a subset of cells takes part in active virus replication. In double-immunofluorescence experiments this subset was found to consist primarily of the T3+ and T8+ phenotype. By infection of preparatively separated T4+ and T8+ T lymphocytes, however, it could be shown that both T-cell subsets were susceptible to HCMV infection as indicated by increases in titer and by DNA kinetics. We conclude from these data that the T lymphocyte might be a target for HCMV in vitro, which is in accordance with in vivo findings in HCMV-infected patients.

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“…CMV shedding from the cervix or in the urine is observed almost exclusively in women under the age of 30 (80). The reasons for this observation are unexplained, yet it is of interest that the majority of congenital CMV infections also occur in infants of women under the age of 30 (78). Current evidence indicates that most symptomatic congenital CMV infections result from the primary infection of the mother (143).…”

Section: Intrauterine and Perinatal Periodsmentioning

confidence: 99%

Acquisition of cytomegalovirus infection: an update.

Forbes¹

1989

Clinical Microbiology Reviews

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Immunobiology of Infection with Human Cytomegalovirus

Cited by 25 publications

References 248 publications

Human Cytomegalovirus Replicates in Primary Human Bone Marrow Cells

Human Cytomegalovirus Replicates in Primary Human Bone Marrow Cells

Replication of human cytomegalovirus in human peripheral blood T cells

Acquisition of cytomegalovirus infection: an update.

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