Alzheimer's disease is a modern scourge and is likely to become increasingly so in the future, with increasing longevity. The disease has been investigated for over one hundred years yet its causes and that of the neuropathological characteristics seen in AD brain are still completely unknown. Evidence for a major causative role of a common virus, herpes simplex virus type 1 (HSV1), acting in c...

Virion assembly represents an elaborate molecular jigsaw, coordinating numerous individual components to construct an infectious agent. For enveloped viruses, such as HIV, influenza and Herpes Simplex Virus-1 (HSV1), a vital piece of this puzzle is the acquisition of a membrane. Unlike viral proteins, this is not produced de novo, but derived directly from existing host membranes. The host’s se...

PURPOSE Oncolytic viruses (OV) based on herpes simplex virus type 1 (HSV1) are being used in clinical trials for a variety of cancers. The OV, rQNestin34.5, uses a nestin promoter/enhancer to selectively drive robust viral replication in malignant glioma cells. We have discovered that this promoter becomes extensively methylated in infected glioma cells, reducing OV efficacy. EXPERIMENTAL DES...

Repeated administration of gene therapies is hampered by host immunity toward vectors and transgenes. Attempts to circumvent antivector immunity include pharmacological immunosuppression or alternating different vectors and vector serotypes with the same transgene. Our studies show that B-cell depletion with anti-CD20 monoclonal antibody and concomitant T-cell inhibition with clinically availab...

Hepatocellular carcinoma (HCC) is a common malignant carcinoma worldwide and the third leading cause of cancer mortality. However, current treatment strategies are not potent enough to combat this disease. Therefore, identification of novel and more effective treatments is crucial. Of the current methods, gene therapy, which targets cancer‐specific expression and limits toxicity, is a new strat...

A transgenic mouse line (Oligo-TTK) was established to monitor oligodendrocyte cell death and myelin formation in the CNS. The expression of a conditionally toxic gene, the herpes simplex virus-1 thymidine kinase (HSV1-TK), was made under control of the MBP (myelin basic protein) gene promoter. A truncated form of the HSV1-TK (TTK) gene was used to avoid both bystander effect resulting from lea...

When employed as a transgene reporter, the herpes simplex type 1 virus (HSV1) thymidine kinase gene (tk) is ectopically expressed in mouse testis. The principal testicular mRNA lacks the 5'-end of the tk reading frame. As a result the principal translation products, P2 and P3, are N-terminally truncated. These co-migrate in SDS-PAGE with polypeptides synthesised during HSV1 infection that were ...

Enveloped viruses employ diverse and complex strategies for wrapping at cellular membranes, many of which are poorly understood. Here, an ultrastructural study of herpes simplex virus 1 (HSV1)-infected cells revealed envelopment in tubular membranes. These tubules were labelled by the fluid phase marker horseradish peroxidase (HRP), and were observed to wrap capsids as early as 2 min after HRP ...

background: herpes simplex virus type 1 is one of the most common viruses among human population. studies demonstrate the essential role of cell mediated immunity, especially cd8+ t cells, in prevention and clearance of hsv1. objective: it is of great importance to improve our knowledge about the kinetics of ctl responses to primary and secondary hsv-1 infection. methods: using a sensitive tech...

To analyze the subcellular trafficking of herpesvirus capsids, the small capsid protein has been labeled with different fluorescent proteins. Here, we analyzed the infectivity of several HSV1(17(+)) strains in which the N-terminal region of the non-essential small capsid protein VP26 had been tagged at different positions. While some variants replicated with similar kinetics as their parental w...