Biomedical subjects

R J Geraghty

Publications and source records attributed to R J Geraghty.

5 recordsLinked to original sources

PubMed1996

HIV-1 particle release mediated by Vpu is distinct from that mediated by p6.

Vpu and the C-terminal peptide of Gag (p6) are both HIV-1-encoded proteins that augment the release of virus particles from cells. We examined the functional relationship between these proteins and their activities during particle release. Our results indicate that efficient HIV-1 particle release from HeLa and Jurkat cells depends on the presence of Vpu. However, Vpu is dispensable for efficient release from Cos cells. In contrast, p6 is required for efficient release from Cos cells but not from Jurkat or HeLa cells. These data suggest that Vpu and p6 have distinct activities in virus exit from different cell lines. Intracellular proteolytic processing of Gag precursor protein is more complete in Cos cells than in HeLa cells. However, this processing has little or no effect on Vpu- or p6-mediated particle release. p6 is required for incorporation of yet another virus protein (Vpr) into cells but our data suggest that Vpr plays no role in p6-dependent particle release. Vpu also facilitates the degradation of CD4 in virus producing cells but, in contrast to particle release, the ability of Vpu to facilitate the degradation of CD4 is not cell line-dependent.

Animals↗

PubMed1993

Human immunodeficiency virus type 1 Vpu has a CD4- and an envelope glycoprotein-independent function.

Vpu is a 16-kDa membrane-associated phosphoprotein that is expressed from the same, singly spliced message as the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein precursor, gp160. Previous studies suggest that Vpu functions in the late stages of viral replication, possibly in virus egression from the cell. Recently, it has been demonstrated that Vpu functions to allow gp160 to be more efficiently processed by disrupting CD4-gp160 complexes generated by transfection of HeLa cells. We show here that the lack of expression of intact Vpu results in a 90% reduction in infectious virus produced over a single round of replication from HeLa cells in the absence of CD4 expression. This reduction persists when HIV-1 particles are pseudotyped with the HIV-2 or amphotropic murine leukemia virus envelope glycoprotein. Pulse-chase analysis of HIV-1 capsid protein (p24) in the absence of CD4 and envelope glycoprotein demonstrates that the rate of virus release is reduced when Vpu is not expressed. Our findings indicate that Vpu has a function involving particle release not dependent on CD4 or envelope glycoprotein expression.

CD4 Antigens↗

PubMed1991

The successful medical management of gastric outflow obstruction associated with the use of non-steroidal anti-inflammatory drugs in the elderly.

One hundred and nineteen consecutive elderly patients with endoscopically diagnosed peptic ulceration were reviewed. Associated gastric outflow obstruction was present in 10.1%. The presenting clinical features differed significantly from typical younger patients and most (11/12) were taking non-steroidal anti-inflammatory drugs, suggesting a possible role for these agents in the pathogenesis of gastric outflow obstruction. These elderly patients have been successfully managed by medical therapy alone.

Aged↗

PubMed1989

Autoimmune haemolytic anaemia associated with malignant peritoneal mesothelioma.

A 57-year-old man with a history of pulmonary asbestosis was incidentally found to have benign mesothelial hyperplasia of the peritoneum at hernia repair. Five months later he developed a Coombs positive haemolytic anaemia of the IgG-C3d type caused by non specific IgG antibodies. At that time no underlying cause for the anaemia was found. The anaemia responded to steroids, but remained steroid dependent. Six months after the diagnosis of the anaemia, a malignant peritoneal mesothelioma was found at laparotomy. The association between malignant mesothelioma and autoimmune haemolytic anaemia has been reported on one previous occasion. The description of a second case suggests that the association is not purely coincidental and that malignant mesothelioma should be added to the list of solid tumours that can be associated with autoimmune haemolytic anaemia. The finding of red blood cells coated with IgG and C3d in this as well as in other cases adds further evidence to the hypothesis that a quinidine type mechanism of haemolysis might be responsible for Coombs positive haemolytic anaemia associated with solid tumours.

Anemia, Hemolytic, Autoimmune↗

PubMedDate not supplied

Cell type-dependence for Vpu function.

Human immunodeficiency virus type 1 Vpu has been shown to facilitate virus release from HeLa cells. We demonstrated that Vpu expression is not required for efficient virus release from Cos 1 and CV-1 cells. A yeast GAL4 transcriptional activation system was used to screen for cellular proteins that may interact with Vpu. One such protein was identified which we provisionally designate "Vpu interactive protein" or VIP.

Animals↗