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Biomedical subjects

D S Latchman

Publications and source records attributed to D S Latchman.

At least 325 records · Page 18Linked to original sources
PubMed1989

Elevated levels of the 90 kd heat shock protein in a proportion of SLE patients with active disease.

The human 90 kd heat shock protein (hsp 90) is associated with the receptor for glucocorticoid hormones and is believed to play a role in the cellular response to corticosteroids. The levels of this protein in the peripheral blood lymphocytes of patients with systemic lupus erythematosus (SLE) have been investigated and compared with those observed in normal individuals and patients with rheumatoid arthritis. Fifteen percent of SLE patients were found to exhibit hsp 90 levels well in excess of those observed in the other groups. These patients all had active disease. The significance of these findings is discussed both in terms of the disease processes occurring in these patients and the efficacy of steroid therapy.

Adrenal Cortex Hormones↗
PubMed1989

Elevation of the levels of SmB, B' and D proteins but not that of the La (SS-B) antigen during HSV infections.

Three Sm proteins, B, B' and D, which are highly immunoreactive in systemic lupus erythematosus (SLE), increase in abundance in Vero cells infected with laboratory strains and clinical isolates of herpes simplex virus (HSV) types 1 and 2. The autoimmune antigen La (SS-B) does not accumulate in identical infections. The significance of the Sm antigen accumulation is discussed in terms of its possible role in HSV infection and in connection with the origin of autoantibodies in SLE.

Animals↗
PubMed1988

Differential regulation of octamer-containing cellular genes by the herpes simplex virus virion protein Vmw65 is mediated by sequence differences in the octamer element.

The gene encoding the U3 SnRNA is transcriptionally induced early in infection with herpes simplex virus (HSV). This effect is due to the action of the HSV virion protein Vmw65 and is dependent upon the octamer motif in the U3 promoter. In contrast the U1 SnRNA gene which also contains an octamer is not activated by Vmw65 in infections or transfections. We show that this is due to sequence differences between the octamers in the U1 and U3 genes. Thus the U3 octamer can confer responsiveness to Vmw65 to truncated U1 or U3 promoters whereas the U1 octamer cannot. The use of Vmw65 as a tool to analyse the role of the octamer sequence in mediating a variety of expression patterns in different genes is discussed.

Animals↗
PubMed1988

Induction and repression of cellular gene transcription during herpes simplex virus infection are mediated by different viral immediate-early gene products.

Nuclear run-off and pulse-labelling techniques have been used to study the changes in transcription rates of a number of cellular genes during infection with Herpes simplex virus. The majority of these genes show a decrease in transcription rate to about 60% of that observed prior to infection. In contrast, a small number of genes are transcriptionally activated during infection. These effects, which occur at a point in infection after the synthesis of viral proteins but prior to the onset of viral DNA synthesis, are mediated by different immediate-early proteins of the virus. Thus we show that, whilst transcriptional activation requires a functional ICP4 protein, repression is dependent upon the presence of another immediate early protein--ICP22.

Acyclovir↗
PubMed1988

A cellular protein related to heat-shock protein 90 accumulates during herpes simplex virus infection and is overexpressed in transformed cells.

A monoclonal antibody produced from mice immunized with HSV-infected cell DNA binding proteins reacts with two cell-encoded polypeptides, p90 and p40, synthesized constitutively by many different cell types and expressed at high levels in transformed cells. In uninfected cells heat shock induces a cytoplasmic accumulation of p90 and in agreement with this we show that p90 is related to hsp90. During HSV-2 lytic productive infection, p90 accumulates to very high levels, such accumulation being detectable by 2 h p.i. In infected cells p90 is distributed throughout the cell, and in contrast to uninfected cells, is also located on the cell surface. Infection with HSV-1 strains causes an accumulation of p40, which has an intracellular location and is absent from the cell surface. These results show that HSV lytic infection results in an accumulation of at least two cell-encoded polypeptides, one of which is related to hsp90.

Animals↗
PubMed1988

The herpes simplex virus type 1 immediate-early protein ICP4 specifically induces increased transcription of the human ubiquitin B gene without affecting the ubiquitin A and C genes.

Lytic infection with herpes simplex virus causes increased ubiquitin gene transcription. This effect is reproduced in cells expressing the viral immediate early protein ICP4 in the absence of other viral proteins but is not seen at the nonpermissive temperature in cells expressing the temperature-sensitive ICP4 protein of HSV-1 tsK. Studies with probes specific to the three human ubiquitin genes indicate that only the Ubi B gene is sensitive to ICP4-mediated induction whereas the Ubi A and C genes are unaffected. The significance of these effects for the mechanism by which ICP4 transcriptionally activates viral and a few cellular genes is discussed.

Gene Expression Regulation↗
PubMed1988

Effect of herpes simplex virus type 2 infection on mitochondrial gene expression.

A cDNA clone derived from the mitochondrial cytochrome oxidase I gene has been used to show that the level of mitochondrially encoded RNA species declines during herpes simplex virus type 2 infection in a manner similar to that for RNA species derived from nuclear genes. In contrast to the situation for nuclear genes, however, no change in the transcription rate of the mitochondrial genome during infection was detected, indicating that post-transcriptional processes alone are responsible for the decline in the levels of mitochondrial RNA species during infection. Two stages in this post-transcriptional degradation have been defined, only one of which is dependent upon viral protein synthesis in the infected cell.

Animals↗
PubMed1988

Cellular polypeptides overexpressed after herpes simplex infection permit virus subtyping and may help diagnose cervical cancer.

The synthesis of cellular macromolecules is inhibited after infection with herpes simplex viruses (HSV) although certain host proteins accumulate to high concentrations as identified by monoclonal antibody TG7A. By western blotting, a polypeptide with a relative molecular weight of 90 kilodaltons was identified in cells infected with type 2 viruses and a polypeptide of 40 kilodaltons relative molecular weight in type 1 infected cells, and virus typing was confirmed by restriction enzyme analysis of viral DNA. Thirty seven clinical isolates from the genital region were subtyped as HSV type 2 and 18 from the orofacial region as type 1 by the different intracellular location of the 90 kilodalton and 40 kilodalton proteins seen on immunofluorescent staining of cells infected with HSV. Expression of these proteins has been associated with cellular transformation due to gene products of HSV or other viruses. Overexpression of the cellular proteins identified by TG7A reactivity was shown to be a marker for cells in cervical smears from patients with CIN III that appeared to be dyskaryotic. Little or no reaction was observed in squamous epithelial cells found in normal or abnormal smears.

Antibodies, Monoclonal↗
PubMed1987

Transcriptional induction of the ubiquitin gene during herpes simplex virus infection is dependent upon the viral immediate-early protein ICP4.

Lytic infection with herpes simplex virus results in transcriptional induction of a cellular gene encoding ubiquitin, causing increased accumulation of ubiquitin RNA and protein in the infected cell. This induction, which is dependent upon viral protein synthesis, does not occur in the HSV-1 mutant tsK which is defective in the gene encoding the viral protein ICP4. Transfected cells expressing the viral ICP4 protein exhibit higher levels of ubiquitin gene transcription than untransfected controls indicating that transcriptional induction can be mediated by the ICP4 protein alone.

Animals↗
PubMed1987

Nuclear accumulation of a heat-shock 70-like protein during herpes simplex virus replication.

A monoclonal antibody defines an antigen, p68, related to hsp70, which is located in nuclei of uninfected exponential cells. Nuclear p68 is released by DNase but not RNase treatment suggesting an association with DNA. Lytic productive infection of confluent quiescent BHK 21 cells with herpes simplex virus type-2 causes p68 to accumulate in nuclei. The effect is specific for HSV-2, and does not occur in HSV-1 infected cells. Maximum nuclear accumulation of p68 requires virus DNA synthesis although a significant accumulation occurs in the absence of such synthesis. It is suggested that the nuclear accumulation of p68 is an aspect of a cellular stress response to lytic infection with HSV-2.

Animals↗
PubMed1987

The human Mr 90,000 heat shock protein and the Escherichia coli Lon protein share an antigenic determinant.

1. A monoclonal antibody (TG7A) reacts with a Mr 90,000 mammalian protein, accumulating during virus infection and heat shock. 2. This protein is encoded by a member of the Mr 90,000 heat shock gene family present in a range of organisms form yeast to man. 3. The antibody also recognises a Mr 94,000 protein in E. coli which similarly accumulates in virus infection and heat shock. 4. This protein has been identified as the Lon protease of E. coli. 5. The shared epitope and similar stress inducibility of the two proteins suggests that a functional and/or evolutionary relationship exists between them.

ATP-Dependent Proteases↗
PubMed1986

Cellular gene induction during herpes simplex virus infection can occur without viral protein synthesis.

Infection of cultured cells with herpes simplex virus (HSV) results in the transcriptional induction of a small number of cellular genes. Although the majority of such genes are dependent upon viral protein synthesis for their induction, a small minority are not. These genes are induced by events occurring prior to the onset of viral protein synthesis, in particular by binding of the virus to the cell surface and cellular entry of the virion. The significance of such cellular gene induction early in viral infection is discussed in terms of virus-cell interaction in general and the mechanism of transformation by HSV in particular.

Cells, Cultured↗
PubMed1986

Isolation of cDNA clones derived from a cellular gene transcriptionally induced by herpes simplex virus.

A small number of cellular proteins accumulate to high levels in cells infected with Herpes Simplex Virus (HSV) despite a generalised repression of most host cell bio-synthesis. An antibody to one such protein has been used to screen a lambda gt11 library and for polysome immunoprecipitation in order to isolate cDNA clones derived from the corresponding gene. The cDNA clones have been used in dot blot and nuclear run-off assays to show that HSV, like other DNA tumour viruses can transcriptionally induce a cellular gene. The mechanism of this effect which is dependent on viral protein synthesis and its possible significance in transformation by HSV are discussed.

Animals↗
PubMed1986

Transcriptional induction of cellular gene expression during lytic infection with herpes simplex virus.

Herpes simplex virus Type 2 causes a severe repression of host cell biosynthesis at a number of levels. We show that despite this, non-viral cDNA clones derived from cellular RNA species which accumulate to high levels after infection can be isolated using differential screening techniques. By using nuclear run-off assays, we have shown that this RNA accumulation is mediated by transcriptional induction of the corresponding cellular genes.

Animals↗
PubMed1986

A filamentous distribution for the herpes simplex virus type 2-encoded major DNA-binding protein.

Monoclonal antibodies reacting with the herpes simplex virus (HSV)-encoded major DNA-binding protein defined an intracellular filamentous network. This network was associated predominantly with the infected cell nucleus and occurred in cells infected with HSV type 2. It did not co-distribute with microfilaments, microtubules or intermediate filaments, and DNA synthesis was required for its formation. We suggest explanations for the occurrence and function of this novel filamentous network structure.

Animals↗