SUMMARYMild proteolysis by trypsin of particles of six potyviruses (bean yellow mosaic virus, clover yellow vein virus, Johnson grass mosaic virus, passion-fruit woodiness virus, potato virus Y and watermelon mosaic virus II) revealed that the N-and C-terminal regions of their coat protein are exposed on the particles' surfaces. The enzyme treatment removed the N-terminal region (30 to 67 amino acids long, depending on the virus) and 18 to 20 amino acids from the C terminus of the coat proteins, leaving a fully assembled virus particle composed of coat protein cores consisting of 216 or 218 amino acid residues. These core particles were indistinguishable from untreated native particles in an electron microscope and were still infectious. The core particles lacked the virus-specific surface epitopes that are recognized by the bulk of the polyclonal antibodies raised against the whole virus particles. Epitopes thought to be groupspecific were located in the trypsin-resistant core protein region. The implications of these findings are discussed in relation to the similar surface location of the N-and Cterminal regions of the coat protein of other rod-shaped plant viruses and the observed common structural features displayed by isometric plant and animal viruses.

An estimated 170 million people worldwide carry the hepatitis C virus (HCV), and in more developed countries the prevalence and incidence of HCV is particularly high among injecting drug users (IDUs). Spontaneous clearance of HCV infection and reinfection is well recognized but the level of protection against further infection conferred by HCV infection and clearance remains uncertain. We conducted a prospective study of HCV infection in IDUs recruited in Melbourne, Australia, using a much shorter median testing interval than in previous studies. Incidences of naive infection and reinfection were calculated by the person-year method and Cox proportional hazards regression used to adjust for covariates. A significantly higher HCV incidence rate was measured in previously infected IDUs (46.8% per year) compared with HCV-naive IDUs (15.5% per year). The hazard ratio for previously infected IDUs compared to HCV-naive IDUs, after adjustment for time-dependent covariates, was 2.54 (95% confidence interval, 1.11-5.78, P > ͦzͦ < 0.05). Viral persistence after reinfection appeared similar to that following naive infection. Conclusion: Our data suggest that HCV infection in IDUs is more likely following prior infection and clearance than in HCV-naive individuals, implying no increased immunity against further infection. This result has important implications for the future development of an HCV vaccine. T he hepatitis C virus (HCV) infects an estimated 170 million people worldwide, and is a significant cause of morbidity and mortality due to cirrhosis and hepatocellular carcinoma. 1 Injecting drug users (IDUs) are the population subgroup at greatest risk of HCV infection in more developed countries, with prevalence rates of 45% or greater per year 2,3 and incidence rates of 25% per year or higher being common. 4,5 HCV differs from the hepatitis B virus and many other infectious viral agents in that infection and the generation of an immune response does not necessarily protect an individual from HCV reinfection or superinfection. Whether infection with HCV and subsequent clearance is even partially protective against further infection is yet to be definitively resolved.In 2002, Mehta et al. 6 reported that previously infected IDUs were significantly less likely to be reinfected, even after accounting for risk behavior. Further reports supported this finding: Grebely et al. 7 reported a significantly lower incidence of HCV reinfection in IDUs than in naive individuals; and Dove et al. 8 detected no reinfections in a small group of ongoing IDUs with previous HCV clearance. A retrospective study by Micallef et al. 9 reported the incidence of HCV reinfection in IDUs was higher than naive infection-31 out of 100 person-years (PYs) (95% confidence interval [CI], 17-62) compared to 17 out of 100 PYs (95% CI, 14-2) although with adjustment for HCV risk behavior variables, the incidence ratio was only marginally greater and was not statistically significant (incidence rate ratio, 1.11; P ϭ 0.8).The importance of the reinfection is...

SUMMARY Dystonia is a brain disorder causing involuntary, often painful movements. Apart from a role for dopamine deficiency in some forms, the cellular mechanisms underlying most dystonias are currently unknown. Here, we discover a role for deficient eIF2α signaling in DYT1 dystonia, a rare inherited generalized form, through a genome-wide RNAi screen. Subsequent experiments including patient-derived cells and a mouse model support both a pathogenic role and therapeutic potential for eIF2α pathway perturbations. We further find genetic and functional evidence supporting similar pathway impairment in patients with sporadic cervical dystonia, due to rare coding variation in the eIF2α effector ATF4/CREB2. Considering also that another dystonia, DYT16, involves a gene upstream of the eIF2α pathway, these results mechanistically link multiple forms of dystonia and put forth a new overall cellular mechanism for dystonia pathogenesis – impairment of eIF2α signaling, a pathway known for its roles in cellular stress responses and synaptic plasticity.

The results of both case-control studies and food testing implicated the novel vehicle of semidried tomatoes as the cause of this hepatitis A outbreak. The outbreak was extensive and sustained despite public health interventions, the design and implementation of which were complicated by limitations in food testing capability and complex supply chains.

Static social network methods are likely to gather information about a minority of patterns of HCV transmission, because of the difficulty of determining historical infection pathways in an established social network of IDUs. Nevertheless, molecular epidemiological methods identified clusters of IDUs with related viruses and provided information about mixed-genotype infection status.