Biomedical subjects

G A Dean

Publications and source records attributed to G A Dean.

28 records · Page 2Linked to original sources

PubMed1992

Hematopoietic target cells of anemogenic subgroup C versus nonanemogenic subgroup A feline leukemia virus.

Feline leukemia viruses (FeLVs) belonging to interference subgroup C induce fatal anemia resembling human pure red cell aplasia (PRCA). Subgroup A FeLVs, although closely related genetically to FeLVs of subgroup C, do not induce PRCA. The determinants for PRCA induction by a molecularly cloned prototype subgroup C virus (FeLV-Sarma-C [FSC]) have been localized to the N-terminal 241 amino acids of the surface glycoprotein (SU) gp70. To investigate whether the anemogenic activity of FSC reflects a unique capacity to infect erythroid progenitor cells, we used correlative immunogold, immunofluorescence, and cytological staining to study prospectively the hemopoietic cell populations infected by either FSC or FeLV-FAIDS-61E-A (F6A), a prototype of subgroup A virus. The results demonstrated that although only FSC-infected animals developed erythrocyte aplasia, the env SU and the major core protein (p27) were expressed in a surprisingly large fraction of the lymphoid, erythroid, and myeloid lineage marrow cells in both FSC- and F6A-infected cats. Between days 8 and 17 postinoculation, gp70 and p27 were detected in 43 to 73% of erythroid, 25 to 75% of lymphoid, and 35 to 50% of myeloid lineage cells, regardless of whether the cats were infected with FSC or F6A. Thus, anemogenic subgroup C and nonanemogenic subgroup A FeLVs have similar hemopoietic cell tropism and infection kinetics, despite their divergent effects on erythroid progenitor cell function. Acute anemia induction by subgroup C FeLV, therefore, does not reflect a unique tropism for marrow erythroid cells but rather indicates a unique cytopathic effect of the SU on erythroid progenitor cells.

Animals↗

PubMed1991

Flow cytometric analysis of T-lymphocyte subsets in cats.

We report a rapid, reliable method for the immunophenotype analysis of feline lymphocytes. Fluorescein isothiocyanate (FITC) conjugated to murine monoclonal antibodies f43, Fel 7 and fCD8 was used to identify phenotypes corresponding to feline T-cells, CD4+ T cells and CD8+ T cells. For isolation of white blood cells, whole blood lysis was faster, less variable and required much less sample than density gradient separation. To identify feline CD4+ and CD8+ cells simultaneously, directly conjugated FITC-fCD8 and phycoerythrin (PE) fCD4 (Fel 7) were used in two-color analysis. The two T cell sub-populations were non-overlapping. Dual-label and single-label values were not significantly different. Mean lymphocyte subset percentages in conventional and specific-pathogen-free (SPF) cats did not differ significantly. These values were: pan T lymphocytes (f43), 54.8%, CD4+ cells (Fel 7), 33.9%, and CD8+ cells (fCD8), 19.1%. Mean CD4/CD8 ratio was 1.9 in normal cats; the range was 1.2-2.6.

Animals↗

PubMed1990

Lymphocyte subset alterations and viral determinants of immunodeficiency disease induction by the feline leukemia virus FeLV-FAIDS.

The FeLV-FAIDS strain of feline leukemia virus consistently induces fatal immunodeficiency. To investigate the immunopathogenesis and viral genetic determinants responsible for the induction of immunodeficiency disease in vivo, we have generated chimeras between the two major viral genomes in the original virus isolate, designated common form clone 61E and major variant clone 61C, which were molecularly cloned directly from DNA of the same animal and tissue. Each of three 61E/C chimeras, containing at minimum a 34-amino-acid segment (including a 6-amino-acid insertion and one amino acid substitution) near the C terminus of the 61C surface glycoprotein (gp70), induced fatal immunodeficiency disease in all (12 of 12) infected animals over a course of 33 +/- 10 weeks. By contrast, animals infected with virus 61E, although persistently antigenemic, remained asymptomatic throughout a 48-week observation period. Beginning 14 weeks after infection, a significant decrease (8 to 10%) in the percent of circulating CD4+ T lymphocytes developed in the 61E/C chimera-infected cats, compared with either 61E-infected or control animals. At this time, no significant changes were seen in CD8 cells, B cells, or mitogen-induced blastogenesis. Prior to this initial decline in CD4 cells, the ability of all antigenemic 61E/C-infected cats to generate a primary antibody response to the T-cell-dependent antigen keyhole limpet hemocyanin was markedly impaired, whereas all 61E-infected cats, one 61E/C-infected but nonviremic cat, and all uninfected control cats produced normal antibody responses. The results reported here demonstrate that a major determinant of in vivo immunodeficiency induction by FeLV-FAIDS is contained within a 34-amino-acid C-terminal segment of its surface glycoprotein and that this gp70 alteration determines the early and persistent deficits in CD4+ T lymphocytes and T-cell-dependent antibody responses. We hypothesize that these early immunologic alterations could result from early deletion of a CD4+ helper T-cell subset.

Animals↗

PubMed1990