The Cytomegaloviruses: Ubiquitous Agents with Protean Clinical Manifestations

Weller, Thomas H.

doi:10.1056/nejm197107222850406

Cited by 486 publications

(206 citation statements)

References 103 publications

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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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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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“…Human cytomegalovirus (HCMV), a member of the herpes group, is a ubiquitous human pathogen that causes, among many other syndromes, multiple forms of embryopathies and fetopathies as a consequence of prenatal infection (Weller, 1971;Stagno et al, 1982). It is increasingly recognized as a cause of severe pneumonitis and septicemia in immunocompromised individuals such as tumor patients undergoing aggressive chemotherapy or persons affected by the acquired immunodeficiency syndrome (AIDS).…”

Section: Introductionmentioning

confidence: 99%

A very strong enhancer is located upstream of an immediate early gene of human cytomegalovirus

Boshart

Weber

Jahn

et al. 1985

Cell

1,098

648

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SummaryA strong transcription enhancer was identified in the genomic DNA (235 kb) of human cytomegalovirus (HCMV), a ubiquitous and severe pathogen of the herpesvirus group. Cotransfection of enhancerless SV40 DNA with randomly fragmented HCMV DNA yielded two SV40-HCMV recombinant viruses that had incorporated overlapping segments of HCMV DNA to substitute for the missing SV40 enhancer. Within HCMV, these enhancer sequences are located upstream of the transcription initiation site of the major immediate-early gene, between nucleotides -118 and -524. Deletion studies with the HCMV enhancer, which harbors a variety of repeated sequence motifs, show that different subsets of this enhancer can substitute for the SV40 enhancer. The HCMV enhancer, which seems to have little cell type or species preference, is severalfold more active than the SV40 enhancer. It is the strongest enhancer we have analyzed so far, a property that makes it a useful component of eukaryotic expression vectors.

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“…The wide range of animal species naturally infected with cytomegalovirus (Weller, 1971) is thus further widened to include the bison.…”

Section: Discussionmentioning

confidence: 99%

Morphogenesis of a Cytomegalovirus from an American Bison Affected with Malignant Catarrhal Fever

Todd

Storz

1983

Journal of General Virology

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SUMMARYA herpesvirus isolated from several organs of an American bison affected with malignant catarrhal fever was cultured in bovine foetal spleen cells and studied by electron microscopy. The fine structural features of the mature virion and the mode of virus morphogenesis were found to be similar to herpesviruses classified in the subgroup cytomegalovirus. The capsids were granular, hexagonal in shape and contained pleomorphic cores in thin sections. Envelopment of the capsids occurred primarily by budding on cytoplasmic membranes which appeared to be formed as extended vesicles of the Golgi apparatus; budding on nuclear membranes was only rarely observed. Cytoplasmic inclusions consisting of granular threads and amorphous electron-dense material were found in association with virions during the late stages of infection. The formation of cytoplasmic inclusions, the morphogenesis and ultrastructure of the virus are all consistent with classification of this virus as a cytomegalovirus.

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The Cytomegaloviruses: Ubiquitous Agents with Protean Clinical Manifestations

Cited by 486 publications

References 103 publications

Comparison of the Immediate Early Polypeptides of Human Cytomegalovirus Isolates

Comparison of the Immediate Early Polypeptides of Human Cytomegalovirus Isolates

A very strong enhancer is located upstream of an immediate early gene of human cytomegalovirus

Morphogenesis of a Cytomegalovirus from an American Bison Affected with Malignant Catarrhal Fever

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