Hepatitis C imposes a significant burden on global healthcare. Chronic infection is associated with progressive inflammation of the liver which typically manifests in cirrhosis, organ failure and cancer. By virtue of elaborate evasion strategies, hepatitis C virus (HCV) succeeds as a persistent human virus. It has an extraordinary capacity to subvert the immune response enabling it to establish chronic infections and associated liver disease. Chemokines are low molecular weight chemotactic peptides that mediate the recruitment of inflammatory cells into tissues and back into the lymphatics and peripheral blood. Thus, they are central to the temporal and spatial distribution of effector and regulatory immune cells. The interactions between chemokines and their cognate receptors help shape the immune response and therefore, have a major influence on the outcome of infection. However, chemokines represent a target for modulation by viruses including the HCV. HCV is known to modulate chemokine expression in vitro and may therefore enable its survival by subverting the immune response in vivo through altered leukocyte chemotaxis resulting in impaired viral clearance and the establishment of chronic low-grade inflammation. In this review, the roles of chemokines in acute and chronic HCV infection are described with a particular emphasis placed on chemokine modulation as a means of immune subversion. We provide an in depth discussion of the part played by chemokines in mediating hepatic fibrosis while addressing the potential applications for these chemoattractants in prognostic medicine.

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Soft x-rays have been shown to be useful for imaging whole cells or microns-thick sections at better than 50-nm resolution with useful native contrast and without the need for staining.1 Soft x-ray radiation within the so-called "water-window" energy regime (between the absorption edge of C (285 eV) and O (540 eV)) produces good absorption contrast from intercellular components but ~10x less contrast from surrounding water. 2 The brightest and most intense sources for soft-x-ray radiation are by far synchrotrons which can produce sub-second images at wavelengths tunable through the soft-x-ray regime. In comparison, the few laboratory sources available currently are limited to one or a few wavelengths and exposure times are source-brightness limited to many seconds or minutes. 3 However laboratory-based (aka "compact") soft-x-ray microscopes have distinct advantages in cost, size, and ability to be located close to the biological laboratory. This paper demonstrates results from the compact soft-x-ray microscope (Gatan Model 550 SXM) we have built for both 2D and 3D imaging of hydrated biological material with 50-60 nm full-period resolution.The SXM has a laser-pulsed plasma (LPP) source 4 based on an ultrafast laser that is focused on a target stream of methanol. The superheated target produces an intense source of soft-x-ray radiation emanating from a region tens of microns across and dominated by the C-VI line (368 eV) with an estimated brightness of >10 10 photons/sr/μm 2 /s. Other transitions are present but are filtered by the condenser system which produces hollow cone illumination at the sample and is subsequently imaged onto a 2Kx2K CCD using an objective zone-plate. The SXM can host multiple objective zone plates (to trade off resolution against depth-of-field) -the current system has a 30-nm zone plate (resolution image shown in Fig. 1a) for high-resolution 2D, and a 48-nm zone plate for tomography.Specimens for the SXM can either be placed on whole TEM grids, 600 μm-wide TEM grids for full-tilt tomography, or inside pipettes. Specimens are then plunge-frozen in liquid ethane to cryo-protect the cells in vitreous ice. Once transferred into the SXM, samples are typically viewed with a built-in fluorescence light-microscope which is extremely useful for locating areas of interest. Switching between light objectives and x-ray objectives takes seconds and positions are precisely correlated. Fast soft x-ray imaging with quality sufficient for navigation can be several images per second and high-quality images take 10-100 seconds.In the experiment shown in Figures 1-3, we sought to measure the thylakoid membrane volume in cyanobacteria -these membranes are essentially invisible in 2D whole cell imaging except where membranes break spherical symmetry. In Figures 1bc, as-acquired projections show the bacteria embedded in ice supported by a lacey carbon film. These films are useful in supporting "droplets" of water containing bacteria and the lacey filaments also serve as a built-in resolution standard throughou...

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