Immediate early antigens in human cytomegalovirus infected cells.
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Publications and source records attributed to S Michelson-Fiske.
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A herpes-type virus that was originally isolated from a cell culture (designated K9V) derived from a tumor biopsy specimen from a patient with Kaposi's sarcoma was partially characterized. The host range of K9V, as determined by the induction of virus-specific cytopathology, synthesis of antigens, and plaque formation, was limited to human cells and particularly to fibroblasts. Immunofluorescence and complement fixation assays confirmed the specificity of the presence of cytomegalovirus (CMV)-type antigens in K9V-infected human fibroblasts. In addition, the density of K9V DNA was consistent with the density of CMV DNA. However, some peculiarities were observed in the K9V strain of CMV. The virus seemed more cell-associated in human fibroblasts than were known laboratory strains: The spread of cytopathology was slow and did not always involve the whole cell sheet, and the total regression of cytopathology with the establishment of a persistent infection was common. Similar characteristics have recently been observed in the Mj strain of CMV, which has been shown to be oncogenic in human fibroblasts.
An isolate (Mira) of cytomegalovirus is shown to replicate in human embryonic lung fibroblasts at supra-optimal temperature (40 degrees C). The ability of the Mira isolate to grow at 40 degrees C decreased as a function of age of cells in which the virus was grown. The unusual morphology of the lesions in late passage cells infected and maintained at 40 degrees C is illustrated.
Cytomegalovirus (CMV), like other members of the herpesviruses, is widely distributed in human populations where the frequency of seropositive individuals is influenced by such factors as age, sex and socio-economic conditions. While this virus causes such diseases as mononucleosis, it is also implicated in autoimmune phenomena and plays an adverse role renal and bone marrow transplantation. Perhaps the most menacing aspect of CMV is the role which it play in congenital malformations resulting from in utero or neo-natal infection. Indeed, this virus is one of the few which can be transmitted vertically. The above mentioned clinical aspects of CMV are discussed here in light of recent clinically studies. The second part of this review will be devoted to the great mass of information recently acquired through experimentation.
Over the last 6 years, our knowledge of the basic characteristics of human cytomegalovirus (HCMV) has been greatly enhanced, especially as concerns the microbiology of this virus. DNA relatedness studies show that there is 80% homology between different strains, regardless of their origin. Studies on the relationships between HCMV and host-cell metabolism reveal that it induces both a virus specific and a cellular DNA polymerase, stimulates ribosomal RNA, induces early protein synthesis and results in the liberation of "intrinsic" interferon. The sequence of appearance of virus-specific antigens, as well as the presence of virus-induced IgG-Fc receptors has been described. New morphological aspects of the virus itself, as well as of the lesions which it provokes, have been observed. Last, but perhaps most important, evidence is accumulating in favor of the oncogenic potential of this virus. These basic aspects of HCMV are presented and discussed herein, along with the effects of various drugs and supra-optimal temperature on the virus and the possibility of preparing a vaccine against it.
New ultrastructual aspects of cytomegalovirus nucleocapsid assembly are illustrated in cells from a Kaposi sarcoma. The occurrence of viral deoxyribonucleoproteins in the form of strands and penetration of these strands into open capsids is illustrated. The geometrical arrangement of the core material of the nucleocapsid is aslo emphasized.
Human lung epithelial cells were productively infected with human cytomegalovirus in vitro. Infectious virus was released up to 8 weeks postinfection. The cells retained their morphological characteristics throughout the period of observation, while simultaneously bearing all the features typical of cytomegalovirus infection.
Functional and morphologic differences between the sensitivity of nucleoli of Rous sarcoma virus-transformed cells and that of newly infected cells to the action of actinomycin D (AD) have been demonstrated by quantitative light and electron microscope autoradiography and utilized to investigate the function of the nucleolus in the early stages of infection. After a pulse exposure to low doses of AD, increased RNA synthesis is induced within 80 minutes in the fibrillar portion of the nucleolus by infection. A concomitant increase in the retention of tritiated AD in the nucleolus and a quantitative redistribution of intranuclear and cytoplasmic DNA label are interpreted as evidence for a virus-induced amplification of the binding sites of AD in nucleolar chromatin.
MRC-5 human diploid cells infected with Simian Sarcoma Virus from woolly monkey (SSV-1) were not transformed but an efficient replication of non transforming SiLV was demonstrated. Increase of virus reverse transcriptase activity paralleled cell replication during successive passages. Preliminary results concerning the influence of viral infection on the life span and the karyotype of MRC-5 diploid cells will be reported and several implications of these findings discussed.