Showing papers on "Virus published in 1968"

Relation of Burkitt's tumor-associated herpes-ytpe virus to infectious mononucleosis.

Abstract: A herpes-type virus has been detected with remarkable frequency in cell lines derived from Burkitt's lymphomas, leukemic tissues, or buffy coats of a variety of patients and healthy donors.'-8 This agent is being named EB virus (EBV), for convenience, after the cell lines in which it was first observed.' M\\ost of the virus particles seen by electron microscopy in a small proportion of the cells are judged noninfectious because they are defective.\" 9. 10 To date, EBV has been transmissible only to cultured human cells of the hematopoietic system.\"'12 Virus-producing cells are readily detectable by indirect immunofluorescence tests with various human sera or by direct staining with fluorescein isothiocyanate-conjugated human y-globulins.'3'-7 Attempts to identify the agent by appropriate virus-specific immunofluorescence tests have failed. Thus EBV appears to be a new member of the herpes group.'3-\"5 From human serum surveys it is evident that infections by EBV, or a close relative of it, are frequent, and that the agent has a world-wide dissemination.\"3 117, 18 The age distribution of antibodies to EBV among American children parallels that of antibodies to other common viruses, such as measles, mumps, or poliomyelitis in the prevaccination era. 18 Except for the fact that all Burkitt's tumor patients studied thus far'3 1' and a high percentage of patients with carcinomas of the postnasal spaces'9 were found to have high titers of antibodies to EBV antigens, no other suggestive relationship of the virus to known disease entities has been recorded. The present report indicates that EBV is related to, and probably the cause of, infectious mononucleosis. Materials and Methods.-The techniques for growth and maintenance of cell lines derived from Burkitt's tumors have been described, as well as the procedures for preparation of cell smears, detection of EB virus antigens, and corresponding antibodies by immunofluorescence.3, 16 Cells of the EB-3 line were routinely used, which had been kept for 4-7 days on arginine-deficient Eagle's basal medium with 25% fetal calf serum (BME25) obtained by preincubation at 370C for 7 days or merely by omission of the amino acid. The arginine deficiency inhibits cellular growth but increases the number of EBV antigen-producing cells by a factor of 5-10 (to be published). Results.-The indirect immunofluorescence test for antibodies to EB virus was used in a search for illnesses that might be caused by this agent. In one series of tests, paired acute stage and convalescent sera from pediatric patients with unidentifiable viral infections were examined with negative results.18 As another approach, serial sera were tested that had been collected from children in prospective studies of viral infections. Such sets of sera were kindly supplied by Dr. John P. Fox from the \"New York Virus Watch,\" and by Dr. John H. Dingle from the Cleveland Family Study. Of the first group, 33 sets were examined that had been collected over periods of from one to four

Defectiveness of Interferon Production and of Rubella Virus Interference in a Line of African Green Monkey Kidney Cells (Vero)

Abstract: Vero cells, a line of African green monkey kidney cells, failed to produce interferon when infected with Newcastle disease, Sendai, Sindbis, and rubella viruses, although the cells were sensitive to interferon. Further, infection of Vero cells with rubella virus did not result in interference with the replication of echovirus 11, Newcastle disease virus, or vesicular stomatitis virus, even in cultures where virtually every cell was infected with rubella virus. Under the same conditions, BSC-1 cells and other cells of primate origin produced interferon and showed rubella virus interference. The results indicate that the presence of rubella virus in the cell does not in itself exclude multiplication of other viruses and that rubella virus interference appears to be linked to the capability of the cell to produce interferon.

Infectious Mononucleosis: Clinical Manifestations in Relation to EB Virus Antibodies

Abstract: In each of 29 patients with infectious mononucleosis (IM) the development of antibodies against a herpes-type virus (EB virus) has been demonstrated by an indirect immunofluorescence test with a virus bearing cell line (EB-3) derived from a Burkitt lymphoma. These antibodies, absent in pre-illness serum specimens, usually appeared early in the disease, rose to peak levels within a few weeks, and remained at relatively high levels during convalescence. They are clearly distinctive from heterophile antibodies and, unlike the latter, they persist for years, probably for life. Tests on sera from 50 randomly selected college freshmen revealed EB virus antibodies in 12, two of whom had positive histories of IM. Of 38 without demonstrable antibodies none had had IM, but the illness developed in three in the next two years. These and other observations strongly indicate that EB virus, or a closely related one, is the etiologic agent of IM.

Electron Microscopy of Herpes Simplex Virus: I. Entry

Abstract: Although capsids of herpes simplex virus were encountered within phagocytic vesicles, they were more commonly observed free within the cytoplasm. Stages in the release of virus from vesicles were not seen. There appeared to be five distinct steps in the process whereby the virus initiates infection: attachment, digestion of the viral envelope, digestion of the cell wall, passage of the capsid directly into the cytoplasm, and digestion of the capsid with release of the core. Antibody probably interferes with the first two stages. Images

Diabetes Mellitus: Induction in Mice by Encephalomyocarditis Virus

Abstract: Hyperglycemia and lesions of the pancreatic islets of Langerhans developed in some, but not all, adult mice infected with a variant of the encephalomyocarditis virus. Large amounts of virus were recovered from the pancreas during acute stages of infection. At this time blood glucose concentrations were markedly elevated and the islets of Langerhans exhibited focal necrosis and degranulation of beta cells. Evidence of abnormal glucose metabolism persisted for varying periods after recovery from the infection. The islets of Langerhans of chronically hyperglycemic mice were distorted and decreased in size, and the beta cells were degranulated. Encephalomyocarditis virus appears to cause diabetes mellitus by reducing the mass of functional beta cells of the islets of Langerhans.

Protective Effects of Specific Immunity to Viral Neuraminidase on Influenza Virus Infection of Mice

Abstract: Antibody specific for viral neuraminidase can be demonstrated in mice following (i) pulmonary infection with influenza virus, (ii) immunization with ultraviolet-in-activated influenza virus, (iii) immunization with isolated neuraminidase of influenza A(2) virus, and (iv) passive immunization with sera of rabbits immunized with isolated A(2) neuraminidase. Neuraminidase antibody produced by any of these methods exerts a profound inhibiting effect on virus replication in the lungs of mice challenged with strains of virus having homologous neuraminidase protein, even in the absence of hemagglutinating inhibiting antibody to the challenge virus, and results in markedly decreased pulmonary virus titers and diminished lung lesions. These observations suggest that antineuraminidase immunity may play a significant role in the protection against influenza virus challenge observed in mice after infection or artificial immunization.

Antiviral Activity of Antiserum Specific for an Influenza Virus Neuraminidase

Abstract: Antiserum specific for influenza A2 neuraminidase was produced by immunization of rabbits with the purified enzyme which had been isolated by electrophoresis from the proteins of a detergent-disrupted A0A2 influenza virus recombinant [X-7 (F1)]. This recombinant contained hemagglutinin of the A0 subtype and A2 neuraminidase. Antiserum to the isolated A2 neuraminidase did not react in any of four serological tests with A0 or A2 subtype viruses that lacked the A2 enzyme. In contrast, the antiserum inhibited the neuraminidase activity only of wild-type and recombinant viruses containing the A2 enzyme, regardless of the nature of their hemagglutinin proteins. The antiserum caused hemagglutination-inhibition of some, but not all, viruses bearing the A2 enzyme, and it reduced the plaque size or plaque number of all viruses tested that contained A2 neuraminidase. In the chick embryo and in cell culture, low dilutions of antiserum reduced the yield of virus. True neutralization of virus in the chick embryo did not occur. We conclude that an antiserum specific for A2 neuraminidase influenced the yield and release of virus from influenza virus-infected cells.

Electron microscopy of herpes simplex virus. II. Sequence of development

Abstract: Examination of infected cells at sequential intervals after infection revealed that the first viral forms to appear were capsids enclosing cores of low density. Not until the 6th hr were dense cores encountered, and at approximately the same time enveloped virus was seen. Envelopment occurred most frequently in close proximity to the nuclear surface, although the process was also encountered within the nuclear matrix and in the cytoplasm. There was often extensive proliferation of the nuclear membrane. Envelopment of the virus by budding from the cell surface was not observed. It was concluded that enveloped virus consitutes the infectious particle and that the unenveloped capsid is unstable outside the cell. Nevertheless, it is likely that capsids enclosing infectious nucleic acid can pass directly from one cell to another after fusion has taken place.

Replication and plaque assay of influenza virus in an established line of canine kidney cells.

Abstract: A plaque assay system has been developed for types A and B influenza viruses in an established line of canine kidney cells (MDCK-USD). In addition to a homogeneous susceptible cell, consistent plaque production depends on the use of highly purified agar (Agarose). This quantitative system was used to determine the rate of adsorption, synthesis, and thermal inactivation of influenza viruses, as well as to determine a dose response curve. Plaque assays on the MDCK-USD line and the parent MDCK line showed that the latter was more sensitive to A/Swine and A(2)/Japan 305 viruses. Titration of standard virus pools in embryonated eggs and MDCK-USD indicated that the cell culture system was as sensitive as the in ovo assay.

Studies on the Etiology of Marek's Disease. II. Finding of a Herpesvirus in Cell Culture

Abstract: SummaryDuck embryo fibroblast (DEF) monolayer cultures seeded with whole blood from birds inoculated with the JM strain of Marek's disease (MD) and which showed a cytopathic effect (CPE), also contained intranuclear herpes-like virus particles. Complete virus particles with envelope essential for infectivity of herpesviruses were not found in either the infected cells or the extracellular materials of cultures containing such cells. All cultures showing CPE contained virus particles, and when inoculated into susceptible chicks caused MD. Cytopathic effect and viral synthesis could not be induced in fresh DEF cultures with spent media from infected cultures passed through 450 mμ Millipore filters. The perfect correlation obtained between CPE, presence of virus particles, and reproduction of MD by these cells suggests a cause and effect relationship and circumstantially implicates this virus in the etiology of MD.

Inhibition of HeLa Cell Protein Synthesis by the Vaccinia Virion

Abstract: HeLa cell protein synthesis is rapidly suppressed after infection with purified vaccinia virus. This was measured in three ways. (i) In the presence of 5 μg of actinomycin D per ml, viral protein synthesis was prevented and the decline in host protein synthesis was measured directly. (ii) Virus particles irradiated with 800 ergs or more of ultraviolet (UV) light per mm2 are defective in their ability to initiate viral protein synthesis, but they still inhibit host protein synthesis. After addition of UV-irradiated virus, the decline in host protein synthesis was measured. (iii) Polyacrylamide gel electrophoresis was used to distinguish between host- and virus-induced proteins. The following results were obtained. (i) The inhibition of HeLa cell protein synthesis begins within 20 min after infection with purified vaccinia particles. Greater than 95% inhibition occurs within 1 to 4 hr after infection, depending on the viral multiplicity used. (ii) The synthesis of viral ribonucleic acid or viral protein is not required for the inhibition of host protein synthesis. (iii) The ability of the virus particles to inhibit cell protein synthesis is lost after heat or detergent treatment. (iv) The ability of the virus particles to inhibit cell protein synthesis is retained after UV-irradiation. (v) Vaccinia viral protein synthesis in preinfected cells is resistant to the effects of superinfection with UV-irradiated vaccinia particles. (vi) Inhibition of cell protein synthesis is complete and does not involve the continued synthesis of small polypeptide fragments. (vii) A decrease in the size of host polyribosomes rapidly follows infection with vaccinia virus. The results are interpreted as a selective effect of some constituent of the vaccinia virus particle or virus-activated host enzyme on host protein synthesis at a level beyond that of transcription.

Relation between Epstein-Barr viral and cell membrane immunofluorescence of Burkitt tumor cells. I. Dependence of cell membrane immunofluorescence on presence of EB virus.

Abstract: A comparison was made of the immunofluorescence tests for detection of cell membrane and Epstein-Barr virus antigens in cells from Burkitt tumor biopsies or continuous cultures derived therefrom. On the whole, cell membrane fluorescence in established lines appeared to depend not only upon the presence of EBV but to a considerable degree also upon the extent of the persistent viral infection. There was no constant relationship, however, between the results of the two tests and exceptions to the rule were noted. These observations indicate that different antigens are involved in the two tests. Biopsy cells in general and young cultures may reveal strong MIF activity but few, if any, EBV-positive cells. The reverse, the presence of relatively large numbers of EBV antigen-containing cells in the absence of significant MIF reactions, was also noted on occasion in a few established cultures. The possible interpretations of these findings have been discussed.

Infectious Diseases of Children

Abstract: Acquired Immuno Deficiency Syndrome (AIDS) human immuno deficiency virus botulism in infants cytomegalovirus infections diphteria enteroviral infections Epstein-Barr virus infection acute gastroenteritis haemophilus influenza type B (HIB) viral hepatitis herpes simplex virus infections infection in the hospitalized and immunocompetent child Kawasaki's syndrome, measles bacterial meningitis mumps osteomyelitis and supportive arthritis otitis media parovirus infections pertussis (whooping cough) rabies acute respiratory infections rossola rubella sepsis in the newborn sexually transmitted disease smallpox and vaccinia staphylococcal infection streptococcal infections group A tetanus (lockjaw) tick-born infections toxoplasmosis tuberculosis urinary tract infections varicella-zoster virus infections viral infections of the CWS diagnosis of acute exanthematous diseases.

The effect of histocompatibility-2 type on response to the friend leukemia virus in mice

Abstract: Two types of quantitative response to the F-B strain of Friend virus in segregating generations of a cross involving a susceptible (DBA/2 or BALB/c; H-2(2)) and a resistant (C57BL/6; H-2(b)) mouse strain show a marked correlation with the H-2 type of the mice. Essential susceptibility, as determined by the splenomegalic response to high virus doses, is controlled by a single pair of alleles which segregates independently with respect to the H-2 locus. However, relative susceptibility, as determined by the incidence of the splenomegalic response at moderate or low levels of virus dosage, is significantly greater among mice homozygous or heterozygous for the H-2(d) allele than among H-2(b) homozygotes in these populations. In addition, the incidence of recovery from splenomegaly induced by a given level of virus dosage is significantly greater in H-2(b) homozygotes than in segregants of other H-2 types among their littermates. Possible mechanisms responsible for these effects are discussed.

Sequential Protein Synthesis Following Vaccinia Virus Infection

Abstract: Inhibition of HeLa cell protein synthesis and the sequential synthesis of viral proteins were followed by pulse-labeling infected cells with 14C-phenylalanine. Proteins were resolved by polyacrylamide gel electrophoresis. The viral origin of native proteins was confirmed by immunodiffusion. The inhibition of host protein synthesis and the synthesis of early viral proteins occur 1 to 3 hr after infection. This early sequence of events also occurs in the presence of 5-fluorodeoxyuridine, an inhibitor of deoxyribonucleic acid synthesis. Other viral proteins are synthesized at a later time. Those proteins which are not made in the absence of viral deoxyribonucleic acid synthesis can be further subdivided into intermediate and late classes. The intermediate protein is synthesized before the late proteins but does not appear to be a precursor of them. Many more viral polypeptides were resolved by polyacrylamide gel electrophoresis after solubilization of the entire cytoplasmic fraction with sodium dodecyl sulfate. Virion and nonvirion proteins were identified. Kinetic experiments suggested that certain structural proteins as well as certain nonstructural proteins are made early, whereas others of both classes are made primarily at later times.

Identification of the membrane protein and "core" protein of Sindbis virus.

Abstract: Electron micrographs of arbovirus (insect-borne animal viruses) virions suggest that they are composed of an outer lipoprotein envelope and an inner RNA-containing core that has also been assumed to contain proteins.^(1,2) The lipoprotein envelope of the virus is apparently acquired as the core buds through an altered cellular membrane.^2 Pfefferkorn and Hunter^3 analyzed purified preparations of Sindbis virus, a group A arbovirus, and found that 28 per cent of the mass of the virion was lipid. Because several analyses of animal cell membranes have yielded protein-to-lipid ratios of 1.6-2,^(4,5)Pfefferkorn^6 reasoned that the bulk of the total protein of the virion must be in the form of lipoprotein. When it was later found that all the viral protein was synthesized de Lo after infection, the possibility was raised that the protein portion of the virus lipoprotein envelope was, in fact, specified by the virus genome. Because the RNA of this group of viruses is a molecule of about 2.0 X 10^6 daltons,^7 there was reasonable hope that their lipoprotein envelopes might be composed of only one polypeptide chain (or at most a few) combined with a specific set of lipids. The studies here reported indicate that the virion contains only two proteins-one associated with the viral RNA in a "core," the other associated with lipid to form the lipoprotein envelope of the virus.

The Morphological and Biological Effects of Various Antisera on Avian Infectious Bronchitis Virus

Abstract: Summary Biologically, homotypic and heterotypic antisera neutralized avian infectious bronchitis virus significantly more when unheated. Morphologically, using the electron microscope technique of negative staining, there was a clear distinction between the effects of homotypic and heterotypic antisera. Heated homotypic antiserum revealed antibody attached only to the projections of the virus, while with unheated homotypic serum heat labile components could be visualized but no basic change could be seen in particle morphology. Heterotypic serum contained antibodies directed both against the projections and the envelope of the virus. In addition, unheated heterotypic antiserum produced holes approximately 100 A in diameter in the virus membrane, suggesting that a form of virus lysis takes place. Rabbit antiserum prepared against uninfected chick-embryo fibroblasts was able to produce similar holes in the virus envelope and this led us to postulate that the envelope component of avian infectious bronchitis virus is closely related to normal chick host material.

Cross-resistance to the transplantation of syngeneic Friend, Moloney, and Rauscher virus-induced tumors

Abstract: Summary Immunofluorescence data are presented which confirm the previously reported cytotoxic antibody studies suggesting that Friend, Moloney, and Rauscher (FMR) virus-induced lymphomas possess similar surface antigens, not shared by Gross lymphomas. It is not known, however, whether the antigenic relationship demonstrable serologically is, or should necessarily be, demonstrable by transplantation studies. To determine if tumors induced by FMR and Gross virus share transplantation antigens, C57BL/6 mice were pretreated with either infectious FMR viruses, FMR lymphomas, or a Gross lymphoma and challenged with syngeneic FMR and Gross lymphomas. Mice pretreated with any one infectious FMR virus or its induced lymphoma became resistant to the transplantation of all FMR lymphomas, but not to the Gross lymphoma. Immunization with the Gross lymphoma failed to induce resistance to the transplantation of the FMR lymphomas, but also failed to induce resistance to itself. The results strongly suggest that FMR lymphomas possess related or identical transplantation antigens.

Antiviral Activity of Polyacrylic and Polymethacrylic Acids I. Mode of Action in Vitro.

Abstract: Polyacrylic acid (PAA) and polymethacrylic acid (PMAA) were investigated for their antiviral properties in tissue culture. Compared to other related polyanions, as dextran sulfate, polystyrene sulfonate, polyvinyl sulfate, and polyphloroglucinol phosphate, PAA and PMAA were found to be significantly more antivirally active and less cytotoxic. PMAA added 24 hr prior to virus inoculation inhibited viral growth most efficiently but it was still effective when added 3 hr after infection. Neither a direct irreversible action on the virus nor inhibition of virus penetration into the cell could explain the antiviral activity of PMAA. PMAA inhibited the adsorption of the virus to the host cell and suppressed the one-cycle viral synthesis in tissue cultures inoculated with infectious RNA.

Viruses in fungi and interferon stimulation.

Abstract: The active component of statolon—an anti-viral agent—is RNA of viral origin and not a polyanionic polysaccharide as previously thought. This article describes the isolation and some properties of the P. stoloniferum virus which is active in stimulating interferon production. An interferon inducing virus has also been found in a strain of Penicillium funiculosum.

Abnormalities of in vitro lymphocyte responses during rubella virus infections

Abstract: In vitro rubella virus infections of lymphocytes from normal adult humans impaired their responsiveness to phytohemagglutinin (PHA) stimulations; a situation which seemed analogous to the PHA unresponsiveness of peripheral lymphocytes from babies with the congenital rubella syndrome. Such in vitro viral infection of normal cells also decreased the synthesis of normal nucleic acids and structural proteins, and abrogated the enhanced DNA synthesis induced by pokeweed and specific antigen stimulations. Furthermore, it was shown that live rubella virus, but not ultraviolet-irradiated virus, was necessary for the impaired mitogenic responses of normal leukocytes. These observations are interpreted to favor the view that the virus achieves its inhibitory effect on the action of mitogens by interference either directly or indirectly at an intracellular site. Such an action could reduce the functional potential of lymphocytes and impair their effectiveness as immunologically competent cells or as effectors in immunologic reactions.