The hepatitis C virus (HCV) replicates on a membrane protein complex composed of viral proteins, replicating RNA, and altered cellular membranes. Small-molecule inhibitors of cellular lipid-cholesterol metabolism such as 25-hydroxycholesterol, cerulenin, lovastatin, and GGTI-286 all show a negative effect on HCV replication. Perturbation of host cell lipid and cholesterol metabolism can disrupt replication complexes by altering membranous structures where replication occurs. Changes in cholesterol and (or) lipid composition can have a general effect on membrane structure. Alternatively, metabolic changes can exert a more subtle influence over replication complexes by altering localization of host proteins through alterations in lipid anchoring. Here, we use Huh-7 cells harboring subgenomic HCV replicons to demonstrate that 25-hydroxycholesterol, cerulenin, lovastatin, and GGTI-286 do not disrupt the membranous web where replication occurs, whereas cholesterol-depleting agents such as beta-cyclodextrin do. Cellular imaging suggests that the HCV RNA can remain associated with subcellular compartments connected with replication complexes in the presence of metabolic inhibitors. Therefore, at least 2 different molecular mechanisms are possible for the inhibition of HCV replication through the modulation of cellular lipid and cholesterol metabolism.

A virus of typical Herpesvirus morphology was found in papillomas and carcinomas of smelt Osmerus mordax. lcosahedral unenveloped viral nucleocapsids 95 nm in diameter were found in the enlarged nuclei of infected cells. The nuclei contained dispersed granular chromatin that appeared to be producing viral nucleoids. Most cytoplasmic viral particles were enveloped in electron-dense material, and surrounded by a smooth-membraned vesicle. Some vesicles containing viruses were associated with the enlarged Golgi apparatus, the outer nuclear membrane, or the lim~ting membrane of the cell.

A number of microalgae have been implicated in toxicity episodes in cultured shellfish in Eastern Canada. Nitzschia pungens f. multiseries and Prorocentrum lima are two organisms that have been shown to produce the toxins associated with poisonous shellfish. The present study examines these organisms by light microscopy (DIC and fluorescence), and SEM.The pennate marine diatom, N. pungens(fig. 2), has been shown to produce a potent neurotoxin, domoic acid, in pure culture. The distinctive features of this pennate diatom are illustrated in Fig. 1. The silica covering (frustule) consists of parallel rows of costa with multiple rows of minute pores (poroids). P. lima (fig. 5) is a dinoflagellate that has been found to produce a toxin known as okadaic acid. This toxin has been associated with ciguatera, a fish poison, and was implicated in a recent toxic shellfish event in Eastern Canada. The cellulosic thecal plates are adorned with regular, distinctive pattern of pores (fig. 4).