TASK DEFINITION: In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
PROBLEM: Hepatitis C virus (HCV) is a blood-borne pathogen causing acute and chronic hepatitis. A significant number of people chronically infected with HCV develop cirrhosis and/or liver cancer. The pathophysiologic mechanisms of hepatocyte damage associated with chronic HCV infection are not fully understood yet, mainly due to the lack of an in vitro system able to recapitulate the stages of infection in vivo. Several studies underline that HCV virus replication depends on redox-sensitive cellular pathways; in addition, it is known that virus itself induces alterations of the cellular redox state. However, the exact interplay between HCV replication and oxidative stress has not been elucidated. In particular, the role of reduced glutathione (GSH) in HCV replication and infection is still not clear. We set up an in vitro system, based on low m.o.i. of Huh7.5 cell line with a HCV infectious clone (J6/JFH1), that reproduced the acute and persistent phases of HCV infection up to 76 days of culture. We demonstrated that the acute phase of HCV infection is characterized by the elevated levels of reactive oxygen species (ROS) associated in part with an increase of NADPH-oxidase transcripts and activity and a depletion of GSH accompanied by high rates of viral replication and apoptotic cell death. Conversely, the chronic phase is characterized by a reestablishment of reduced environment due to a decreased ROS production and increased GSH content in infected cells that might concur to the establishment of viral persistence. Treatment with the prooxidant auranofin of the persistently infected cultures induced the increase of viral RNA titer, suggesting that a prooxidant state could favor the reactivation of HCV viral replication that in turn caused cell damage and death. Our results suggest that targeting the redox-sensitive host-cells pathways essential for viral replication and/or persistence may represent a promising option for contrasting HCV infection.

SOLUTION: Counteraction of HCV-Induced Oxidative Stress Concurs to Establish Chronic Infection in Liver Cell Cultures

PROBLEM: Chemical denaturant sensitivity of the dimeric main protease from severe acute respiratory syndrome (SARS) coronavirus to guanidinium chloride was examined in terms of fluorescence spectroscopy, circular dichroism, analytical ultracentrifuge, and enzyme activity change. The dimeric enzyme dissociated at guanidinium chloride concentration of ,0.4 M, at which the enzymatic activity loss showed close correlation with the subunit dissociation. Further increase in guanidinium chloride induced a reversible biphasic unfolding of the enzyme. The unfolding of the C-terminal domain-truncated enzyme, on the other hand, followed a monophasic unfolding curve. Different mutants of the full-length protease (W31 and W207/W218), with tryptophanyl residue(s) mutated to phenylalanine at the C-terminal or N-terminal domain, respectively, were constructed. Unfolding curves of these mutants were monophasic but corresponded to the first and second phases of the protease, respectively. The unfolding intermediate of the protease thus represented a folded C-terminal domain but an unfolded N-terminal domain, which is enzymatically inactive due to loss of regulatory properties. The various enzyme forms were characterized in terms of hydrophobicity and size-and-shape distributions. We provide direct evidence for the functional role of C-terminal domain in stabilization of the catalytic N-terminal domain of SARS coronavirus main protease.

SOLUTION: Reversible Unfolding of the Severe Acute Respiratory Syndrome Coronavirus Main Protease in Guanidinium Chloride

PROBLEM: Do stress hormones such as corticosterone enhance bird susceptibility to mosquitoes in ways that enhance rates of coinfection? Does this then enhance pathogen emergence? Interactions between pathogens are often mediated by the hosts immune system [1] . Two recent experimental papers suggest that interactions between the immune system and corticosterone may be important in mediating synergistic interactions between pathogens that enhance rates of co-infection in birds. As part of a long term study on the effect of the bacterial pathogen Mycoplasma gallisepticum in house finches Haemorhous mexicanus, Dana Hawley and her team asked the question to what extent are the stress hormones that are important for energy mobilization and regulation of the immune system influenced by experimental infection with the bacterium M. gallisepticum [2] . They found that corticosterone levels increased after house finches were infected with M. gallisepticum, decreased again to pre-infection levels once the infection was cleared, and that individuals with greater disease severity had the highest corticosterone concentrations. Trying to identify factors that influence West Nile virus transmission, Lynn Martin and his team started from the premise that stress hormones might represent a key link between individual-level of infection, population-levels of parasite transmission, and zoonotic disease risk. They experimentally manipulated zebra finch Taeniopygia guttata stress hormones by implanting corticosterone-filled silastic tubules and examined subsequent feeding preferences, feeding success, and productivity of mosquito vectors [3] . Despite performing more frequent

SOLUTION:
Stress hormones bring birds, pathogens and mosquitoes together HHS Public Access