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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Herpes simplex virus (HSV) is one of the best studied examples of viral ability to remain latent in the human nervous system and to cause recurrent disease by reactivation. Intensive effort was directed in recent years to unveil the molecular viral mechanisms and the virus-host interactions associated with latent HSV infection. The discovery of the state of the latent viral DNA in nervous tissues and of the presence of latency-associated gene expression during latent infection, both differing from the situation during viral replication, provided important clues relevant to the pathogenesis of latent HSV infection. This review summarizes the current state of knowledge on the site of latent infection, the molecular phenomena of latency, and the mechanisms of the various stages of latency: acute infection, establishment and maintenance of latency, and reactivation. This information paved the way to recent trials aiming to use herpes viruses as vectors to deliver genes into the nervous system, an issue that is also addressed in this review.
Mol Neurobiol 1993
PMID:Molecular biology of herpes simplex virus type 1 latency in the nervous system. 839 44

p53 is a nuclear phosphoprotein whose function is classified as tumor suppression. Studies have shown that p53 functions by binding to p53 DNA recognition sequences and regulates transcription of growth-regulatory genes. Various p53 recognition sequences have recently been identified. pOST2 contained two copies of a palindromic high-affinity DNA-binding sequence for p53; the other p53 recognition sequences included p53-binding fragments found in the human ribosomal gene cluster (pRGC) region and in the murine muscle creatine kinase promoter (pMCK). The purpose of this study was to compare the abilities of various p53 recognition sequences to mediate transcription in the presence of endogenously produced wild-type (wt) or mutant p53. Three p53-responsive chloramphenicol acetyltransferase (CAT) reporter constructs (pOST2, pRGC, and pMCK) that contain one or two copies of p53 recognition sequences upstream of a herpes thymidine kinase (TK) promoter and CAT reporter cDNA were constructed. Either a p53-responsive gene or a control reporter gene was transfected into human carcinoma cell lines (having various p53 mutations) either with or without a wt or mutant p53 expression vector. CAT activity was assayed to measure transactivation through the various p53-responsive elements. We showed that pOST2 had a greater ability to mediate transactivation by p53 than either pRGC or pMCK. p53 with a mutation at either codon 175 or 248 was unable to transactivate a reporter gene with pOST2, pRGC, or pMCK. We found it interesting that pOST2, but not pRGC or pMCK, was able to mediate transactivation in cell lines that produce codon 273-mutant p53. These findings suggest that various sensitivities of the different p53-responsive elements to specific mutant and wt p53s may be an important factor in the role of p53 as a transcriptional activator both under normal physiological conditions and during carcinogenesis.
Mol Carcinog 1996 Jun
PMID:p53 transactivation through various p53-responsive elements. 864 24

The human herpes simplex virus type 1 (HSV-1) transactivator VP16 and its homolog from bovine herpes-virus 1 (BHV-1) can each recruit the human homeodomain protein Oct-1 into a transcriptional regulatory complex. Here, we show that these two Oct-1 coregulators possess similar, if not identical, homeodomain recognition properties but possess different virus-specific cis-regulatory specificities: the HSV-1 VP-16 protein activates transcription from the HSV-1 VP16 response element, and the BHV-1 VP16 protein activates transcription from the BHV-1 VP16 response element. A distinct 3-bp segment, the D segment, lying 3' of the canonical TAATGARAT motif (where R is a purine) in the VP16 response element is responsible for the differential cis element recognition and transcriptional activation by these two homeodomain coregulators. These results demonstrate how a single homeodomain protein can direct differential transcriptional regulation by selective association with homologous homeodomain coregulators.
Mol Cell Biol 1996 Jun
PMID:Differential control of transcription by homologous homeodomain coregulators. 864 8

Infectious agents have been proposed as possible etiological factors in sporadic cases of Alzheimer disease (AD), herpes simplex type 1 virus (HSV1) being a likely candidate. We have detected laten HSV1 in brain from AD patients and from aged normal individuals, using polymerase chain reaction (PCR), in the regions most affected in the disease. In contrast, we have not detected another neurotropic herpes virus, varicella zoster (VZV), in any brains. We have postulated that HSV1 reactivates periodically, and that a host or viral characteristic determines the degree of damage caused by the resulting acute infection-with much greater damage in the case of AD patients. We have therefore examined a host factor-the apolipoprotein E (apoE) genotype, since the E4 allele is a known risk factor in the disease. We have found that the risk of developing AD is much greater in those who are HSV1-positive in brain and who possess an apoE4 allele than for those with only one of these factors.
Mol Chem Neuropathol
PMID:Neurotropic viruses and Alzheimer disease. Interaction of herpes simplex type 1 virus and apolipoprotein E in the etiology of the disease. 887 52

Patients suffering from the acquired immune deficiency syndrome (AIDS) have a 20000-fold increased risk of developing a severe form of Kaposi's sarcoma (KS), a previously rare malignancy involving sharply defined nodular lesions of the skin and/or oral mucosa. Epidemiological evidence has long suggested that an infectious agent is the probable cause of KS. Recently sequences from a putative new herpesvirus have been found to be associated with KS in virtually 100% of the cases analyzed. The suspected etiological agent, a new human herpesvirus termed Kaposi's sarcoma associated herpes virus (human herpes virus 8) has now been propagated in cell culture. This significant advance should form the basis for a detailed analysis of the pathogenetic mechanisms involved in the development of KS.
J Mol Med (Berl) 1997 Jan
PMID:Kaposi's sarcoma: is the hunt for the culprit over now? 902 Mar 81

Interleukin-2 (IL-2) gene therapy alone and in combination with the herpes thymidine kinase gene (tk) was used to evaluate immunological responses and antitumor effects in head and neck cancer. Established floor of mouth squamous cell carcinomas in C3H/HeJ mice were directly injected with recombinant adenoviral vectors carrying both therapeutic and control genes. One week after adenoviral gene transfer, only the animals treated with combination IL-2+tk or tk alone demonstrated significant tumor regression. Residual tumors were harvested for microscopic evaluation and immunohistochemistry staining, which revealed a predominance of CD8+ lymphocytes in the tumor beds of the animals treated with IL-2. To evaluate the systemic immune effects of IL-2, animals treated with single or combination gene therapy received a second site challenge with parental tumor cells or a heterologous but syngeneic sarcoma cell line. Mice treated with combination IL-2 and tk demonstrated a protective systemic immunity specific to the parental tumor cell line, whereas no systemic immune response was evident in mice receiving IL-2 alone. In a separate experiment, a range of concentrations of the adenovirus IL-2 vector were used to treat established tumors. Even with the maximal single-dose adenovirus concentration, IL-2 alone was ineffective as a single therapy. These results support the use of adenovirus-mediated gene transfer of IL-2 as an effective immunotherapy when used adjuvantly with the tk "suicide gene".
Mol Endocrinol 1997 Jun
PMID:The role of interleukin-2 in combination adenovirus gene therapy for head and neck cancer. 917 Dec 30

The tyrosine phosphatase IA-2 is a molecular target of pancreatic islet autoimmunity in type 1 diabetes. T-cell epitope peptides in autoantigens have potential diagnostic and therapeutic applications, and they may hold clues to environmental agents with similar sequences that could trigger or exacerbate autoimmune disease. We identified 13 epitope peptides in IA-2 by measuring peripheral blood T-cell proliferation to 68 overlapping, synthetic peptides encompassing the intracytoplasmic domain of IA-2 in six at-risk type 1 diabetes relatives selected for HLA susceptibility haplotypes. The dominant epitope, VIVMLTPLVEDGVKQC (aa 805-820), which elicited the highest T-cell responses in all at-risk relatives, has 56% identity and 100% similarity over 9 amino acids (aa) with a sequence in VP7, a major immunogenic protein of human rotavirus. Both peptides bind to HLA-DR4(*0401) and are deduced to present identical aa to the T-cell receptor. The contiguous sequence of VP7 has 75% identity and 92% similarity over 12 aa with a known T-cell epitope in glutamic acid decarboxylase (GAD), another autoantigen in type 1 diabetes. This dominant IA-2 epitope peptide also has 75-45% identity and 88-64% similarity over 8-14 aa to sequences in Dengue, cytomegalovirus, measles, hepatitis C, and canine distemper viruses, and the bacterium Haemophilus influenzae. Three other IA-2 epitope peptides are 71-100% similar over 7-12 aa to herpes, rhino-, hanta- and flaviviruses. Two others are 80-82% similar over 10-11 aa to sequences in milk, wheat, and bean proteins. Further studies should now be carried out to directly test the hypothesis that T-cell activation by rotavirus and possibly other viruses, and dietary proteins, could trigger or exacerbate beta-cell autoimmunity through molecular mimicry with IA-2 and (for rotavirus) GAD.
Mol Med 1998 Apr
PMID:T-cell epitopes in type 1 diabetes autoantigen tyrosine phosphatase IA-2: potential for mimicry with rotavirus and other environmental agents. 960 76

The "reverse" tetracycline repressor (rtR) binds a specific DNA element, the tetracycline operator (tetO), only in the presence of tetracycline, or derivatives such as doxycycline (dox). Fusion of rtR to the transcriptional activation domain of herpes virus protein VP16 produces a eukaryotic transactivator protein (rtTA). rtTA has previously been shown to allow dox-dependent transcription of transgenes linked to tetO sequences in mammals. To adapt this system to Drosophila, the Actin5C promoter was used to drive constitutive expression of rtTA in transgenic flies. Three reporter constructs, each encoding E. coli beta-galactosidase (beta-gal), were also introduced into transgenic flies. In one reporter seven tetO sequences were fused to the Adh core promoter. The other two reporter constructs contain seven tetO sequences fused to the hsp70 core promoter. Feeding of transgenic Drosophila containing the rtTA construct and any one of the three reporter constructs with dox caused up to 100-fold induction of beta-gal. Dox induced beta-gal expression in all tissues, in larvae and in young and senescent adults. Induction of beta-gal in adults had no detectable effect on life span. These results suggest the potential usefulness of this system for testing specific genes for effects on Drosophila development and aging.
Mol Gen Genet 1998 Jun
PMID:Doxycycline-induced transgene expression during Drosophila development and aging. 967 Oct 25

Follicular dendritic cell tumours are rare malignancies derived from the follicular dendritic cells of lymphoid follicles. These tumours have been associated with Epstein-Barr virus infections and with the hyaline vascular subtype of Castleman's disease. Because many examples of Castleman's disease have been associated with Kaposi's sarcoma associated herpes virus (HHV-8), this study uses polymerase chain reaction technology to examine five cases of follicular dendritic cell tumours for HHV-8. One of these cases had previously been documented to arise from pre-existing Castleman's disease. HHV-8 DNA was not detected in any of the follicular dendritic cell tumours examined, or in the original case of Castleman's disease. These findings suggest that HHV-8 plays no role in the aetiology of follicular dendritic cell tumours and the cause of this tumour remains obscure.
Mol Pathol 1998 Jun
PMID:HHV-8 is not associated with follicular dendritic cell tumours. 985 Mar 42

Kaposi's sarcoma (KS) presents in four clinicopathological types namely classical/sporadic (CKS), endemic African (EKS), iatrogenic (IKS) and that associated with AIDS (AKS). Recently a putative herpes virus (HHV-8) was described and shown to be present in all four types of KS. The immunological status of patients with EKS has been conflicting. In this study total leucocyte counts, total lymphocyte counts and lymphocyte subsets of patients with EKS and AKS were determined by flow cytometry and compared to those of healthy HIV-1 seronegative controls. Results show that 50% of EKS lesions were of nodular type. Patients with EKS had significantly lower levels of CD4+ T- lymphocytes and CD4:CD8 ratio but significantly higher CD8+ T-lymphocytes compared to controls. Patients with AKS had significantly lower levels of CD4+ T-lymphocytes and also CD4:CD8 ratios but significantly higher percentage of CD8+ T-lymphocytes when compared with EKS patients. These findings indicate that in both forms of KS there is a certain degree of immunological disturbance which is more conspicuous in AKS because of HIV infection and suggests that HIV-1 acts synergistically with the aetiological agent (HHV-8) to cause a more aggressive type of KS.
Int J Mol Med 1998 Jun
PMID:Immunological profile of endemic and epidemic Kaposi's sarcoma patients in Dar-es-Salaam, Tanzania. 985 34


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