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Biomedical subjects

S G Norley

Publications and source records attributed to S G Norley.

31 records · Page 2Linked to original sources
PubMed1990

Immunological studies of the basis for the apathogenicity of simian immunodeficiency virus from African green monkeys.

Potential reasons for the lack of pathogenicity of the simian immunodeficiency virus SIVagm in its natural host, the African green monkey (AGM, Cercopithecus aethiops), were investigated with respect to immunological mechanisms. The functional immune response of monkeys to infection was similar (though not identical) to that of humans to infection with human immunodeficiency virus type 1 (HIV-1). In the sera of infected animals, neutralizing antibodies were found to be low or absent, and in particular there was no neutralization of the various isolates by homologous sera. There was no detectable antibody/complement cytotoxicity, though AGM sera were able to initiate antibody-dependent cellular cytolysis of infected cells in the presence of healthy effector peripheral blood lymphocytes. As in the human/HIV system, macrophages from AGMs are readily infected by SIVagm. Two possibly important differences between the AGM/SIVagm system and the human/HIV system are (i) the low immune response of the AGMs to the core protein of SIVagm and (ii) the significantly lower inhibitory effect of SIVagm proteins on the proliferation of AGM lymphocytes.

Animals↗
PubMed1990

Productive infection of both CD4+ and CD4- human cell lines with HIV-1, HIV-2 and SIVagm.

Human monolayer cells of various origins were shown to be susceptible to infection by HIV-1, HIV-2 and simian immunodeficiency virus obtained from African green monkeys (SIVagm). Immunoperoxidase staining revealed infection of 2-7% of the monolayer cells, although in order to achieve infection approximately 50-fold more virus was necessary than with CD4(+)-permissive lymphoma cells. No CD4-receptor antigen expression by fibroblastoid cells was detectable by immunofluorescence using several monoclonal antibodies (MAbs), although a low level of CD4-specific messenger RNA expression was revealed by Northern analysis (with the exception of Tera-1 and RD cells). Attempts to block viral infection by anti-CD4 MAbs indicated a CD4 receptor-mediated mechanism for all lines tested except RD cells. We conclude that a low level of CD4-receptor expression is sufficient to allow infection of fibroblastoid cells. The infectability of a CD4-negative cell line indicates a second pathway of cellular infection, possibly mediated by a cellular receptor distinct from the CD4 molecule.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Retroviruses and malignant lymphoma.

Retroviruses are single stranded RNA viruses that possess a unique enzyme, reverse transcriptase. This enzyme facilitates the synthesis of double stranded DNA intermediates able to integrate into the genome of the host cell. Although primarily a means of remaining latent, this integration can have the effect of transforming the cell to malignant growth, either by activation of growth control genes in cis or trans, or by insertion of an integrated oncogene. Malignant lymphomas caused by retroviruses occur in animals from mice to man, and have increasing economic and clinical significance. HTLV-1 is the causative agent of adult T-cell leukemia/lymphoma which is endemic in certain discrete locations of the world and has been implicated in a variety of other disorders. The fact that the virus seems to be spreading through groups of intravenous drug abusers in much the same way as the AIDS virus is a cause for concern.

Animals↗
PubMed1987

Inhibition of herpes simplex virus replication in the mouse cornea by drug containing immunoliposomes.

Monoclonal antibody to HSV glycoprotein D was derivatized with palmitic acid and incorporated into liposomes. These immunoliposomes bound specifically to intact mouse corneas infected with HSV-1 in vitro. Furthermore, in yield reduction assays, anti-gD immunoliposomes loaded with acyclovir proved far more effective at inhibiting viral replication in the cornea than free drug or drug delivered in untargeted liposomes. Site-specific sustained release immunoliposomes of this type are potentially an improved vehicle for drug delivery in the treatment of ocular HSV.

Acyclovir↗
PubMed1986

Targeting of drug loaded immunoliposomes to herpes simplex virus infected corneal cells: an effective means of inhibiting virus replication in vitro.

The goal of our studies was to develop liposomes containing antiviral drugs and targeted with antiviral antibody (immunoliposomes) that would be effective at inhibiting replication of herpes simplex virus (HSV) in vitro. To achieve this, a monoclonal antibody to glycoprotein D of HSV was derivatized with palmitic acid and was incorporated into the lamellae of dehydration-rehydration vesicles. The gD containing immunoliposomes were shown to bind specifically to HSV-infected rabbit corneal cells in vitro, whereas control immunoliposomes prepared with a monoclonal antibody of the same class as the anti-gD failed to preferentially bind to virus-infected cells. The gD immunoliposome binding was inhibitable by pretreatment with rabbit anti-HSV serum but not by aggregated normal serum. Thus liposome binding was judged to represent an antigen-antibody reaction not binding to Fc receptors expressed by cells infected with HSV. Immunoliposomes loaded with iododeoxyuridine (IUDR) leaked drug rapidly at 37 degrees C, whereas acyclovir (ACV)-loaded liposomes still contained 48% of drug after 24 hr at 37 degrees C. The ACV-liposomes retained 44% of drug after 14 days at 4 degrees C. The ability of immunoliposomes to inhibit virus replication was compared with that of untargeted and empty liposomes by means of virus yield assays in vitro, Immunoliposomes loaded with either IUDR or ACV inhibited virus replication, although ACV-containing immunoliposomes were the most efficacious. The implications of our in vitro results for the development of immunoliposomes suitable for the treatment of ocular herpes infection are briefly discussed.

Acyclovir↗
PubMed1985

The role of antibody in protection against African swine fever virus.

Intraperitoneal immunization of pigs with anti-African swine fever virus (ASFV) antibody protected them against the effects of challenge with ASFV. This protection, which was exemplified by a reduction in pyrexia and viraemia plus an increased survival time, appeared to be mediated through the effects of complement-dependent antibody-mediated cytotoxicity (CDAC) or antibody dependent cell mediated cytotoxicity (ADCC). Experiments suggested that the reduction in viraemia was associated with complement lysis whereas protection was conferred by ADCC.

African Swine Fever↗
PubMed1984

Cytotoxic lymphocytes induced by African swine fever infection.

The generation of lymphocytes cytotoxic to African swine fever virus infected testis cells during in vivo infection is described. Peripheral blood lymphocytes from 16 pigs developed cytotoxicity seven to eight days after infection but the lysis was not restricted to autologous cells.

African Swine Fever↗
PubMed1983

Interactions of porcine alveolar macrophages and bone marrow cells with African swine fever virus and virus-infected cells.

Virus yields from porcine alveolar macrophages (AM) infected with African swine fever virus (ASFV) were greater and were achieved more rapidly, when inoculated at a high multiplicity of infection (MOI) than at low MOI. The difference was related to a lower percentage of cells becoming infected after low MOI inoculation. The reduced yields after low MOI were not caused by prolongation of the culture time, by bacterial endotoxins or by production of inhibitory substances by infected AM. Virus-infected AM were not susceptible to lysis in antibody-dependent cell mediated cytotoxicity (ADCC) assays and this was apparently due to a paucity of viral antigen expressed on the cell surface. Uninfected AM did not act as effectors in ADCC. Porcine bone marrow (PBM) cells were effective in mediation of ADCC and their activity was reduced after ASFV infection. Cells separated into adherent and non-adherent populations, depleted by carbonyl iron treatment or separated by Ficoll-Hypaque centrifugation, all showed effector activity in ADCC. The effector cells were not mature neutrophils or lymphocytes and were probably granulocytic precursors.

African Swine Fever Virus↗
PubMed1983

Investigation of porcine natural-killer cell activity with reference to African swine-fever virus infection.

The natural killing of the human myeloid leukaemia cell line by pig mononuclear cells was investigated in an 18 hr assay; the most active natural-killer (NK) effectors were those cells not adhering to nylon-wool columns or rosetting with sheep red blood cells. Mononuclear cells cultured in the presence of African swine-fever virus maintained NK activity. Pigs infected with African swine-fever virus exhibited a suppressed NK activity, possibly due to the sensitivity of NK cells to increased temperatures. The possible role of NK cells in recovery from African swine fever is discussed.

African Swine Fever↗
PubMed1983

Effector mechanisms in the pig. Antibody-dependent cellular cytolysis of African swine fever virus infected cells.

Antibody dependent cellular cytolysis (ADCC) against African swine fever virus infected nucleated cells was investigated in a porcine system. Of the peripheral blood components examined, only neutrophils acted as effectors. Lymph node derived cells displayed no ADCC activity. In vitro yield reduction assays suggested that neutrophil mediated ADCC may play a role in recovery from African swine fever virus infection.

African Swine Fever↗
PubMed1982

Complement-mediated lysis of African swine fever virus-infected cells.

Using an homologous pig system, th lysis of African swine fever virus-infected cells by antibody and complement was investigated. The optimal conditions necessary for lysis are described, and it was found that the system was unique amongst reported virus infections in that infected cells were lysed by the classical complement pathway and not the alternative pathway. Development of antibody capable of initiating complement-mediated lysis was relatively late in the infected pig, although functional in vitro assays suggested that it might act as a significant effector mechanism. Investigations of sera taken from pigs infected with varying African swine fever isolates indicate that the assay may provide a means of discriminating between strains.

African Swine Fever↗