Oncolytic viral therapy with a combination of HF10, a herpes simplex virus type 1 variant and granulocyte-macrophage colony-stimulating factor for murine ovarian cancer.

Ovarian cancer is the most frequent cause of gynecological cancer-related mortality as a majority of patients are diagnosed at an advanced stage with intraperitoneal dissemination because of the absence of initial symptoms. Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays an important role in the maturation of specialized antigen-presenting cells. In this study, we utilized a herpes simplex virus (HSV) amplicon expressing murine GM-CSF combined with HF10 (mGM-CSF amplicon), a highly attenuated HSV type 1 strain functioning as a helper virus to strengthen anti-tumor immune response, for the treatment of ovarian cancer with intraperitoneal dissemination.

Immunization with a highly attenuated replication-competent herpes simplex virus type 1 mutant, HF10, protects mice from genital disease caused by herpes simplex virus type 2.

Genital herpes is an intractable disease caused mainly by herpes simplex virus (HSV) type 2 (HSV-2), and is a major concern in public health. A previous infection with HSV type 1 (HSV-1) enhances protection against primary HSV-2 infection to some extent. In this study, we evaluated the ability of HF10, a naturally occurring replication-competent HSV-1 mutant, to protect against genital infection in mice caused by HSV-2.

Antitumor activities of valproic acid on Epstein-Barr virus-associated T and natural killer lymphoma cells.

Epstein-Barr virus (EBV), which infects B cells, T cells, and natural killer (NK) cells, is associated with multiple lymphoid malignancies. Recently, histone deacetylase (HDAC) inhibitors have been reported to have anticancer effects against various tumor cells. In the present study, we evaluated the killing effect of valproic acid (VPA), which acts as an HDAC inhibitor, on EBV-positive and -negative T and NK lymphoma cells.

Herpes simplex virus requires poly(ADP-ribose) polymerase activity for efficient replication and induces extracellular signal-related kinase-dependent phosphorylation and ICP0-dependent nuclear localization of tankyrase 1.

Tankyrase 1 is a poly(ADP-ribose) polymerase (PARP) which localizes to multiple subcellular sites, including telomeres and mitotic centrosomes. Poly(ADP-ribosyl)ation of the nuclear mitotic apparatus (NuMA) protein by tankyrase 1 during mitosis is essential for sister telomere resolution and mitotic spindle pole formation. In interphase cells, tankyrase 1 resides in the cytoplasm, and its role therein is not well understood.

Herpes simplex virus induces the marked up-regulation of the zinc finger transcriptional factor INSM1, which modulates the expression and localization of the immediate early protein ICP0.

Background: Herpes simplex viruses (HSVs) rapidly shut off macromolecular synthesis in host cells. In contrast, global microarray analyses have shown that HSV infection markedly up-regulates a number of host cell genes that may play important roles in HSV-host cell interactions. To understand the regulatory mechanisms involved, we initiated studies focusing on the zinc finger transcription factor insulinoma-associated 1 (INSM1), a host cell protein markedly up-regulated by HSV infection.

Herpes simplex virus UL56 interacts with and regulates the Nedd4-family ubiquitin ligase Itch.

Background: Herpes simplex virus type 2 (HSV-2) is one of many viruses that exploits and modifies the cellular ubiquitin system. HSV-2 expresses the tegument protein UL56 that has been implicated in cytoplasmic transport and/or release of virions, and is a putative regulatory protein of Nedd4 ubiquitin ligase. In order to elucidate the biological function of UL56, this study examined the interaction of UL56 with the Nedd4-family ubiquitin ligase Itch and its role in the regulation of Itch.

Non-engineered, naturally oncolytic herpes simplex virus HSV1 HF-10: applications for cancer gene therapy.

Oncolytic HSV-1 has been developed as a novel anticancer agent. According to the properties and functions of HSV-1 encoded proteins, several genes have been targeted for engineering of oncolytic HSV-1. As a result, a variety of strategies have been applied to the engineering of oncolytic HSV-1.

Microarray analysis of transcriptional responses to infection by herpes simplex virus types 1 and 2 and their US3-deficient mutants.

Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) induce similar responses in infected cells and animals but differ in several significant respects. Previous studies have shown that defects in the US3-encoded protein kinase greatly affect both viruses in their interactions with cells and hosts. To investigate the impact of infection with HSV-1, HSV-2 and their US3-deficient mutants (DeltaUS3) on cellular transcriptional responses, we performed a global microarray analysis on human epithelial HEp-2 cells that were mock-infected, or infected with wild-type (WT) HSV-1, HSV-2 and their DeltaUS3 mutants.

Regulation of IL-27p28 gene by lipopolysaccharide in dendritic DC2.4 cells.

To elucidate the regulation of IL-27p28 gene, we analyzed the promoter region of the gene in DC2.4 cells with or without lipopolysaccharide (LPS)-treatment. The results indicate that a region (-648 to -364) of p28 promoter was responsible for LPS-induction.

Role of IL-27-producing dendritic [corrected] cells in Th1-immunity polarization in Lewis rats.

Lewis and Brown Norway rats are entirely different with respect to the polarization of their immune responses (Th1 and Th2, respectively). We found that naive Lewis rat splenocytes treated in vitro with heat-killed Mycobacterium tuberculosis (Mtb) upregulate the expression of both subunits of IL-27 (IL-27p28 and EBI3). Mtb treatment caused naive Lewis rat splenocytes to express 4.