A high-content AlphaScreen™ identifies E6-specific small molecule inhibitors as potential therapeutics for HPV head and neck squamous cell carcinomas.

The incidence of human papillomavirus-positive head and neck squamous cell carcinoma (HPV-HNSCC) has increased dramatically over the past decades due to an increase in infection of the oral mucosa by HPV. The etiology of HPV-HNSCC is linked to expression of the HPV oncoprotein, E6, which influences tumor formation, growth and survival. E6 effects this oncogenic phenotype in part through inhibitory protein-protein interactions (PPIs) and accelerated degradation of proteins with tumor suppressor properties, such as p53 and caspase 8.

Octopaminergic Signaling Mediates Neural Regulation of Innate Immunity in Caenorhabditis elegans.

Upon pathogen infection, the nervous system regulates innate immunity to confer coordinated protection to the host. However, the precise mechanisms of such regulation remain unclear. Previous studies have demonstrated that OCTR-1, a putative G protein-coupled receptor for catecholamine, functions in the sensory neurons designated "ASH" to suppress innate immune responses in It is unknown what molecules act as OCTR-1 ligands in the neural immune regulatory circuit.

Modulation of apoptotic pathways by human papillomaviruses (HPV): mechanisms and implications for therapy.

The ability of the host to trigger apoptosis in infected cells is perhaps the most powerful tool by which viruses can be cleared from the host organism. To avoid elimination by this mechanism, human papillomaviruses (HPV) have developed several mechanisms that enable the cells they infect to elude both extrinsic and intrinsic apoptosis. In this manuscript, we review the current literature regarding how HPV-infected cells avoid apoptosis and the molecular mechanisms involved in these events.

Small molecule inhibitors of the HPV16-E6 interaction with caspase 8.

High-risk strains of human papillomaviruses (HPVs) cause nearly all cases of cervical cancer as well as a growing number of head and neck cancers. The oncogenicity of these viruses can be attributed to the activities of their two primary oncoproteins, E6 and E7. The E6 protein has among its functions the ability to prevent apoptosis of infected cells through its binding to FADD and caspase 8.

Differential display of grouper iridovirus-infected grouper cells by immunostaining.

Grouper iridovirus (GIV) is one of the most devastating infectious pathogens of aquaculture fish. When infecting a susceptible cell line, such as GK-2, GIV causes antigenic changes in host cellular proteins. To understand the host gene expression characteristics after viral infection, we developed an immunostaining method to screen differentially expressed genes of fish cells in response to GIV infection using phage display complementary DNA libraries.

Iridovirus Bcl-2 protein inhibits apoptosis in the early stage of viral infection.

The grouper iridovirus (GIV) belongs to the family Iridoviridae, whose genome contains an antiapoptotic B-cell lymphoma (Bcl)-2-like gene. This study was carried-out to understand whether GIV blocks apoptosis in its host. UV-irradiated grouper kidney (GK) cells underwent apoptosis.