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Biomedical subjects

C Grose

Publications and source records attributed to C Grose.

At least 73 records · Page 4Linked to original sources
PubMed1989

Epstein-Barr virus: the hematologic and oncologic consequences of virus-host interaction.

Varicella-zoster virus (VZV) and Epstein-Barr virus (EBV) are two of the human herpesviruses. The others include herpes simplex virus (HSV) type 1, HSV type 2, and cytomegalovirus (CMV). In a series of two articles, we review the clinical diseases caused by VZV and EBV infections; we pay particular attention to the manifestations of these two viral infections in immunosuppressed and immunocompromised patients. In addition to the clinical reviews, each of the two articles begins with a brief discussion of the molecular aspects of VZV and EBV, respectively; this introduction describes features of the genome and immunogenic viral proteins which have clinical relevance. A model for pathogenesis is included. The first review concerns VZV infections. Recent data about the DNA sequence of the entire VZV genome are included, as well as a review of the VZV glycoproteins. Primary VZV infection (chickenpox) and VZV reactivation (zoster) are described in detail in both healthy individuals and people with cancer. The decade-long VZV vaccine trials in children with leukemia receive special emphasis because they have engendered considerable interest and debate. The second review (published here) covers EBV infections. This virus has been implicated in the causation of a wide variety of human hematological and oncological disorders, besides classical infectious mononucleosis. In particular, Burkitt's lymphoma, nasopharyngeal carcinoma, and lymphoproliferative disorders are strongly associated with EBV infection of the transformed cells. In addition, immunologically mediated cytopenias occasionally follow EBV infection. Finally, treatment regimens with antiviral chemotherapy and other agents are discussed for both VZV and EBV infections.

Burkitt Lymphoma↗
PubMed1989

IgM and IgG responses to varicella-zoster virus p32/p36 complex after chickenpox and zoster, congenital and subclinical infections, and vaccination.

Varicella-zoster virus (VZV) directs the synthesis of a nonglycosylated polypeptide complex with two prominent species with relative molecular masses of 32,000 and 36,000; the p32/p36 complex is present in both the viral nucleocapsid and the nuclear matrix of the infected cell. We have now further characterized the humoral immune response of VZV-infected humans to this complex and established that it is a major viral antigen. Antibodies to VZV p32/p36 were detected in sera from patients with both primary VZV infection (chickenpox) and VZV reactivation (zoster); the response after zoster was more pronounced. When the IgM and IgG components of the immune response were distinguished, IgM to the viral nucleoproteins was observed following chickenpox and zoster and, to a lesser extent, in recipients of VZV vaccine. An IgM response to VZV p32 also was detected during intrauterine VZV infection and subclinical VZV infection.

Antibodies, Viral↗
PubMed1989

Cellular and humoral immunity to varicella zoster virus glycoproteins in immune and susceptible human subjects.

To further delineate the immune responses that protect against serious primary varicella zoster virus (VZV) infection and inhibit viral reactivation, antibody responses and T lymphocyte reactivity to three major VZV glycoproteins, gpI, gpII, and gpIII, were studied. Individual viral glycoproteins were purified using murine monoclonal antibodies. Cellular immunity was measured by lymphocyte proliferation. Antibody responses were tested in enzyme-linked immunosorbent assays. Individual glycoproteins induced VZV-specific proliferation by mononuclear cells from 15 of 20 immune subjects. Serologic responses to the VZV glycoproteins occurred in 16 of 20 immune subjects. Of note, gpII served as a potent T and B cell antigen during both acute infection and convalescence. Cell-mediated responses to the glycoprotein antigens represented proliferation by T lymphocytes and required antigen presentation by adherent mononuclear cells. These findings indicate that virally encoded glycoproteins contain epitopes that stimulate VZV-specific cellular and humoral immune responses.

Antibodies, Viral↗
PubMed1989

Phosphorylation of varicella-zoster virus glycoprotein gpI by mammalian casein kinase II and casein kinase I.

Varicella-zoster virus (VZV) glycoprotein gpI is the predominant viral glycoprotein within the plasma membranes of infected cells. This viral glycoprotein is phosphorylated on its polypeptide backbone during biosynthesis. In this report, we investigated the protein kinases which participate in the phosphorylation events. Under in vivo conditions, VZV gpI was phosphorylated on its serine and threonine residues by protein kinases present within lysates of either VZV-infected or uninfected cells. Because this activity was diminished by heparin, a known inhibitor of casein kinase II, isolated gpI was incubated with purified casein kinase II and shown to be phosphorylated in an in vitro assay containing [gamma-32P]ATP. The same glycoprotein was phosphorylated when [32P]GTP was substituted for [32P]ATP in the protein kinase assay. We also tested whether VZV gpI was phosphorylated by two other ubiquitous mammalian protein kinases--casein kinase I and cyclic AMP-dependent kinase--and found that only casein kinase I modified gpI. When the predicted 623-amino-acid sequence of gpI was examined, two phosphorylation sites known to be optimal for casein kinase II were observed. Immediately upstream from each of the casein kinase II sites was a potential casein kinase I phosphorylation site. In summary, this study showed that VZV gpI was phosphorylated by each of two mammalian protein kinases (casein kinase I and casein kinase II) and that potential serine-threonine phosphorylation sites for each of these two kinases were present in the viral glycoprotein.

Amino Acids↗
PubMed1989

Congenital varicella-zoster virus infection and the failure to establish virus-specific cell-mediated immunity.

Varicella-zoster virus (VZV) is one of the six human herpesviruses. The viral genome encodes five glycoproteins among its 70 open reading frames; these have been designated gpI to gpV. VZV causes the primary disease chickenpox, usually in children, after which the virus remains latent in the dorsal root ganglia. Later in life, VZV reactivates and causes the disease zoster. VZV can also infect the fetus of a pregnant woman who contracts chickenpox. The fetopathy is unusual in that it more closely resembles zoster than chickenpox. To determine whether the intrauterine immune response is impaired following VZV infection, the humoral and cellular immune responses were first defined in healthy children and adults following chickenpox. All produced virus-specific antibody responses to the viral glycoproteins; in addition, their lymphocytes proliferated when stimulated by both crude VZV antigen and purified glycoprotein products. The fetal immune system generated immunoglobulin M-specific antibodies to the individual VZV glycoproteins. However, no lymphocyte proliferative response was detected. Thus, these studies suggest that the fetus may not be able to mount a cell-mediated response to VZV antigens and that this impaired immunity may contribute to the severe sequelae.

Antibodies, Viral↗
PubMed1988

Biotinylated and radioactive DNA probes for detection of varicella-zoster virus genome in infected human cells.

We have developed and compared two DNA dot hybridization methodologies with similar probes (radioisotope-labelled and biotin-labelled) to detect varicella-zoster virus (VZV) DNA in three different cell cultures at varying times post-infection. Control cultures included uninfected monolayers of the same cells. Cellular DNA was isolated by a standard phenol extraction method, after which the DNA was quantified, serially diluted and blotted onto nitrocellulose or nylon membranes. The VZV DNA probe, which consisted of the large Hind III A fragment (27 of the total 125 kbp), was produced in two separate nick translation systems. The first contained 100 microCi [32P] and 0.4 microgram Hind III fragment A of the varicella genome, while the second probe employed a biotin-7-dATP analogue and 1.0 microgram of the Hind III fragment A. Direct visualization on the membrane or the exposed radiographic film showed a dot of varying intensity whenever viral genome was detected with either the biotin or the radioactive probe, respectively. With the [32P]-labelled probe, we detected VZV genomic sequences within 0.5 microgram total DNA at 12 h post-infection. This amount corresponded to approximately 5-10 pg of viral DNA. By comparison, hybridization with the biotin-labelled probe required 0.5-1.0 micrograms total DNA from infected cells. Similar tests on DNA extracted from uninfected cell samples were negative with both probes.

Biotin↗
PubMed1988

Sabin inactivated trivalent poliovirus vaccine: first clinical trial and seroimmunity survey.

The most widely used poliovaccine in the United States contains the three live attenuated strains originally produced by Sabin. An inactivated ("killed") formulation of this trivalent polio vaccine has now been prepared. Before testing this new vaccine, we assessed the poliovirus immune status of 39 healthy adult males between the ages of 20 and 44 years and found that 69% had detectable (titer greater than or equal to 1:4) neutralizing antibody to all three types of poliovirus, whereas 31% lacked antibody to 1 or more types even though they had a history of childhood polio immunization. Of interest, the lowest levels of neutralizing antibody were found among young adults in their late 20s, 2 of whom lacked antibody to all 3 polio types. When the Sabin inactivated trivalent poliovirus vaccine was initially administered to 12 seropositive volunteers, all responded with rising titers of neutralizing antibody that persisted for at least 18 months (range, 1:249 to 1:4948). The new vaccine was also given to a second group of 9 individuals with little or no detectable neutralizing antibody to at least one poliovirus type and again all vaccinees manifested a humoral immune response to poliovirus. Except for transient local tenderness at the injection site, no untoward reactions to immunization were observed. Thus, this Phase I study (1) confirmed earlier reports that titers of poliovirus antibody may decline to undetectable levels by early adulthood and (2) demonstrated that adults previously immunized with poliovirus vaccine responded rapidly to all 3 poliovirus types (within 7 days) upon reimmunization with Sabin inactivated trivalent vaccine whether or not there was preexisting detectable antibody.

Adult↗
PubMed1988

Role of cytoplasmic vacuoles in varicella-zoster virus glycoprotein trafficking and virion envelopment.

Varicella-zoster virus (VZV) encodes several glycoproteins which are present on both mature viral envelopes and the surfaces of infected cell membranes. Mechanisms of VZV glycoprotein transport and virion envelopment were investigated by both continuous radiolabeling and pulse-chase analyses with tritiated fucose in VZV-infected cells. We studied in detail the large cytoplasmic vacuoles which were present in infected cells but absent from uninfected cells. The specific activity in each subcellular compartment was defined by quantitative electron microscope autoradiography, using a cross-fire probability matrix analysis to more accurately assess the individual compartment demarcated by the silver grains. By these techniques, we documented a progression of activity originating in the Golgi apparatus and traveling through the post-Golgi region into virus-induced cytoplasmic vacuoles and finally to areas of the cellular membrane associated with the egress of viral particles. Significant amounts of radiolabel were not observed in the nucleus, and only low levels of radiolabel were associated with the cellular membrane not involved with the egress of viral particles. In addition, immunolabeling of Lowicryl-embedded VZV-infected cells demonstrated the presence of VZV glycoproteins within cytoplasmic vacuole membranes as well as on virion envelopes. These observations suggested that cytoplasmic vacuoles harbored VZV-specified glycoproteins and were also the predominant site of VZV virion envelopment within the infected cell. Neither enveloped nor unenveloped viral particles were observed within the Golgi apparatus itself.

Autoradiography↗
PubMed1987

Magnetic resonance imaging of the brain in childhood herpesvirus infections.

We used magnetic resonance imaging (MRI) to evaluate nine children with neurologic disorders caused by infections with members of the herpesvirus family. MRI studies were abnormal in eight children and demonstrated a wide range of central nervous system lesions, including cystic encephalomalacia, ventricular enlargement, cerebral atrophy and focal parenchymal lesions. When compared with conventional computed tomographic scanning, MRI was more sensitive in detecting abnormalities of white matter and in defining the extent of parenchymal lesions. These studies indicate that MRI scans are highly useful in children with herpesvirus infections involving the central nervous system.

Brain↗