Latent cytomegalovirus infection in blood donors

Intranuclear inclusions typical of cytomegalovirus infections were Wrst noticed in 1881 by German scientists who thought they represented protozoa. After viruses were grown in cell cultures, Weller, Smith and Rowe independently isolated and grew CMV from man and mice in [1956][1957]. Antibodies in 30-100% of normal adults indicate not only a past infection, but the presence of a present latent infection. The presence of CMV DNA in tissues and most organs surveyed indicates the ubiquity of latent infection. CMV disease requires the virus and some deWciency of immunity such as occurs in the immature fetus, in AIDS, and in transplant patients on immunosuppressive drugs. Antiviral agents can inhibit CMV replication but they cannot prevent or cure latent infections. A pharmacological approach using the many leads in understanding latency is needed. Keywords Antiviral therapy · CMV in AIDS · CMV after transplantation · Discovery of CMV · Epidemiology of CMV · Latent infection by CMV Discovery of cytomegalovirusRibbert [1] wrote that in 1881, he saw large cells in sections of the kidney of a luetic stillborn and in the parotid gland of children which he was unable to interpret until he saw the report of Jesionek and Kiolemenoglou ( Von Glahn and Pappenheimer [4] noted that Lipschuetz [5] had discovered intranuclear inclusion containing cells in lesions in man infected by herpes zoster and herpes genitalis. Thus they believed such abnormal cells were produced by viruses, and they doubted that they were related to protozoa. This was the Wrst indication that cells with intranuclear inclusions might be related to a group of related viruses, now known as the herpesviridae.Farber and Wolbach [6] found such inclusion bearing cells in the salivary glands of 26 out of 183 children examined after death from diverse causes. This was the Wrst approximation of the fact that infection by cytomegalovirus is highly frequent.By 1932, 25 cases of a rare lethal congenial infection characterized by petechiae, hepatosplenomegaly, and intracerebral calciWcation had been described. All of them had cells with typical intranuclear inclusions. Wyatt et al. [7] suggested the name, "generalized cytomegalic inclusion disease (CID)", although its viral etiology was not yet known. A uniform site of involvement were cells of the renal tubules. They suggested that the disease might be diagnosed during life by searching for cells with inclusions in urinary sediments.Following this clue, Fetterman [8] made a cytological preparation from the urine sediment of a suspected case, and made the Wrst intravitum diagnosis of CID.Minder [9] Wrst saw by electronmicroscopy 199 nm particles, suggestive of a virus, in the clear halo around the intranuclear inclusion of pancreatic cells in a case of CID.

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“…None of the children were ill. This degree of seroconversion, or infection, is consistent with 18 other studies in normal subjects [40].…”

Section: Mononucleosissupporting

confidence: 81%

“…But Wnding such cases of viremia in the normal adult population is extremely unusual. Despite repeated attempts, there is only one positive report in the literature [40]. It is more likely that viral transmission is eVected by blood cells that contain latent, non-lytic virus which are then reactivated in the recipient.…”

Section: Mononucleosismentioning

confidence: 99%

The history of cytomegalovirus and its diseases

2007

Med Microbiol Immunol

181

133

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“…As well as producing a variety of syndromes such as cytomegalic inclusion disease, interuterine death, congenital defects and interstitial pneumonia in transplant patients (Weller, 1971), CMV can be maintained in the latent state (Diosi et aL, 1969). Furthermore, transformation studies with hamster embryo fibroblasts (Albrecht & Rapp, 1973) and human embryo fibroblasts (Geder et al, 1976) have suggested that CMV may have oncogenic potential.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Immediate Early Polypeptides of Human Cytomegalovirus Isolates

Js¹,

Preston²

1981

Journal of General Virology

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421 SUMMARYThe in vivo and in vitro synthesized immediate early (IE) polypeptides of three isolates of human cytomegalovirus (CMV) have been compared by SDSpolyacrylamide gel electrophoresis. Of the 11 IE polypeptides detected early in infection, one was very abundant and had a different apparent mol. wt. depending on the isolate. This difference may be useful in the classification of CMV into strains.There is growing awareness of the importance of cytomegalovirus (CMV) as a human pathogen. As well as producing a variety of syndromes such as cytomegalic inclusion disease, interuterine death, congenital defects and interstitial pneumonia in transplant patients (Weller, 1971), CMV can be maintained in the latent state (Diosi et aL, 1969). Furthermore, transformation studies with hamster embryo fibroblasts (Albrecht & Rapp, 1973) and human embryo fibroblasts (Geder et al., 1976) have suggested that CMV may have oncogenic potential.Although there exist many isolates of CMV, it is not known how these relate to each other. It is unclear to what extent CMV isolates can be classified into different strains, if distinct strains are always isolated from the same clinical source, or whether all isolates are capable of producing the range of syndromes associated with CMV. Studies on the antigenic relatedness of CMV isolates using complement fixation and cross-neutralization tests have not been conclusive (Michelson-Fiske, 1977;Waner & Weller, 1978). DNA-DNA renaturation kinetics have shown a high degree of genetic homology (80 %) between different CMV isolates, and although studies of CMV DNA with restriction endonucleases have demonstrated some differences between isolates, these do not fall into patterns which could be used to group these isolates (Kilpatrick et aL, 1976). Another approach has been to analyse the polypeptides of the purified virion by SDS-polyacrylamide gel electrophoresis (Gupta et al., 1977), but the four strains studied (AD169, C87, Burke and Towne) showed great similarities even between their major capsid proteins. This paper reports a difference between three laboratory strains of CMV which emerged during a study of the immediate early (IE) polypeptides of several isolates of CMV, and which may be useful as a diagnostic tool.The cells used in the experiments were the Flow 2002 line of human embryo lung fibroblasts and the viruses were the CMV isolates AD169, Davis and Towne (see Kilpatrick et al., 1976 for their origin). For the in vivo studies, monolayers of cells in 30 mm diam. dishes were infected with virus at a m.o.i, of 5 in the presence of 50 ag/ml cycloheximide (CH) (Sigma) to inhibit protein synthesis. Uninfected controls were treated with 0.2 ml phosphate-buffered saline (PBS). After adsorption at 37 °C for 1 h, the monolayers were washed three times and then overlaid with Eagle's medium supplemented with-10 % foetal calf serum containing 50 #g/ml CH. At 12 h post-infection (p.i.), 5/~g/ml actinomycin D (Act D) (Sigma) was added to prevent further transcription, and 15 min later the plates ...

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“…However, it has been isolated from healthy donors only rarely (Diosi et al, 1969). Immunohistochemical detection methods might be expected to lack the sensitivity necessary to detect latent viral gene expression directly, although one recent report using immunohistochemical methods suggests that immediate early viral proteins are present in many cell types (Toorkey & Carrigan, 1989).…”

Section: Introductionmentioning

confidence: 99%

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

Taylor‐Wiedeman

Sissons

Borysiewicz

et al. 1991

Journal of General Virology

650

478

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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.

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Latent cytomegalovirus infection in blood donors

Cited by 170 publications

References 24 publications

The history of cytomegalovirus and its diseases

The history of cytomegalovirus and its diseases

Comparison of the Immediate Early Polypeptides of Human Cytomegalovirus Isolates

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

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