Summary Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; ...

CD8 ؉ T cell responses play a key role in governing the outcome of hepatitis C virus (HCV) infection, and viral evolution enabling escape from these responses may contribute to the inability to resolve infection. To more comprehensively examine the extent of CD8 escape and adaptation of HCV to human leukocyte antigen (HLA) class I restricted immune pressures on a population level, we sequenced all non-structural proteins in a cohort of 70 chronic HCV genotype 1a-infected subjects (28 subjects with HCV monoinfection and 42 with HCV/human immunodeficiency virus [HIV] coinfection). Linking of sequence polymorphisms with HLA allele expression revealed numerous HLA-associated polymorphisms across the HCV proteome. Multiple associations resided within relatively conserved regions, highlighting attractive targets for vaccination. Additional mutations provided evidence of HLA-driven fixation of sequence polymorphisms, suggesting potential loss of some CD8 targets from the population. In a subgroup analysis of mono-and co-infected subjects some associations lost significance partly due to reduced power of the utilized statistics. A phylogenetic analysis of the data revealed the substantial influence of founder effects upon viral evolution and HLA associations, cautioning against simple statistical approaches to examine the influence of host genetics upon sequence evolution of highly variable pathogens. Conclusion: These data provide insight into the frequency and reproducibility of viral escape from CD8 ؉ T cell responses in human HCV infection, and clarify the combined influence of multiple forces shaping the sequence diversity of HCV and other highly variable pathogens. (HEPATOLOGY 2007;46:339-349.) R ecent studies suggest that immune control of hepatitis C virus (HCV) is possible 1-3 and the role of CD8 T cells is supported by studies linking particular human leukocyte antigen (HLA) class I alleles with control of HCV. 4 How viral infection persists in the face of an activated host immune response is poorly understood. Several mechanisms have been suggested that may contribute to the failure to contain HCV: these include impairment of cellular effector functions, 3,5 suppression of antigen-specific cells by regulatory T cells, 6-8 dendritic cell dysfunction, 9 T cell exhaustion, 10,11 or deletion of antigen-specific T cells in the liver. 12 However, persistence of HCV may also be facilitated by viral evolution that enables evasion of host immune responses occurring over the course of an individual infection. In the chimpanzee model, a strong association has been demonstrated between viral persistence and the development of CD8 escape mutations. 13,14 Moreover, recent studies have begun to clarify the propensity for viral escape from CD8 ϩ

A B S T R A C TPorcine transmissible gastroenteritis virus (TGEV) is one of the major etiological agents of viral enteritis and fetal diarrhea in suckling piglets. In this study, a TGEV JS2012 strain was isolated from the feces of piglets in Jiangsu Province, China. The phylogenetic analysis showed that TGEV JS2012 was placed between the Purdue and the Miller clusters. Analysis of recombination confirmed that TGEV JS2012 is a natural recombinant strain between Miller M6 and Purdue 115. Similar to Miller M6, virulent Purdue and China strain TS, in S gene the JS2012 maintained genetic integrity and the characteristics of the TGEV virulent strains. In vivo, TGEV JS2012 caused 100% mortality in newborn piglets, indicating the strong pathogenicity of this isolate. These results reveal that the JS2012 is a novel natural recombinant TGEV with high virulence. Our findings provide valuable information about genetic diversity and infection mechanism of the coronavirus family.