Genome scale evolution of myxoma virus reveals host-pathogen adaptation and rapid geographic spread

The evolutionary interplay between myxoma virus (MYXV) and the European rabbit (Oryctolagus cuniculus) following release of the virus in Australia in 1950 as a biological control is a classic example of host-pathogen coevolution. We present a detailed genomic and phylogeographic analysis of 30 strains of MYXV, including the Australian progenitor strain Standard Laboratory Strain (SLS), 24 Australian viruses isolated from 1951 to 1999, and three isolates from the early radiation in Britain from 1954 and 1955. We show that in Australia MYXV has spread rapidly on a spatial scale, with multiple lineages cocirculating within individual localities, and that both highly virulent and attenuated viruses were still present in the field through the 1990s. In addition, the detection of closely related virus lineages at sites 1,000 km apart suggests that MYXV moves freely in geographic space, with mosquitoes, fleas, and rabbit migration all providing means of transport. Strikingly, despite multiple introductions, all modern viruses appear to be ultimately derived from the original introductions of SLS. The rapidity of MYXV evolution was also apparent at the genomic scale, with gene duplications documented in a number of viruses. Duplication of potential virulence genes may be important in increasing the expression of virulence proteins and provides the basis for the evolution of novel functions. Mutations leading to loss of open reading frames were surprisingly frequent and in some cases may explain attenuation, but no common mutations that correlated with virulence or attenuation were identified.This work was funded in part by grant R01 AI093804 from the National Institute of Allergy and Infectious Diseases, National Institutes of Health. E.C.H. is funded by an NHMRC Australia Fellowship. D.C.T. is funded by an ARC Future Fellowship

Global phylogeography and ancient evolution of the widespread human gut virus crAssphage

Microbiomes are vast communities of microorganisms and viruses that populate all natural ecosystems. Viruses have been considered to be the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared with that of other environments. Here, we investigate the origin, evolution and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboration, we obtained DNA sequences of crAssphage from more than one-third of the world's countries and showed that the phylogeography of crAssphage is locally clustered within countries, cities and individuals. We also found fully colinear crAssphage-like genomes in both Old-World and New-World primates, suggesting that the association of crAssphage with primates may be millions of years old. Finally, by exploiting a large cohort of more than 1,000 individuals, we tested whether crAssphage is associated with bacterial taxonomic groups of the gut microbiome, diverse human health parameters and a wide range of dietary factors. We identified strong correlations with different clades of bacteria that are related to Bacteroidetes and weak associations with several diet categories, but no significant association with health or disease. We conclude that crAssphage is a benign cosmopolitan virus that may have coevolved with the human lineage and is an integral part of the normal human gut virome

Global phylogeography and ancient evolution of the widespread human gut virus crAssphage

Microbiomes are vast communities of microorganisms and viruses that populate all natural ecosystems. Viruses have been considered to be the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared with that of other environments. Here, we investigate the origin, evolution and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboration, we obtained DNA sequences of crAssphage from more than one-third of the world’s countries and showed that the phylogeography of crAssphage is locally clustered within countries, cities and individuals. We also found fully colinear crAssphage-like genomes in both Old-World and New-World primates, suggesting that the association of crAssphage with primates may be millions of years old. Finally, by exploiting a large cohort of more than 1,000 individuals, we tested whether crAssphage is associated with bacterial taxonomic groups of the gut microbiome, diverse human health parameters and a wide range of dietary factors. We identified strong correlations with different clades of bacteria that are related to Bacteroidetes and weak associations with several diet categories, but no significant association with health or disease. We conclude that crAssphage is a benign cosmopolitan virus that may have coevolved with the human lineage and is an integral part of the normal human gut virome

Swedish physicians' perspectives on work and the medical care system--II: The cases of child and maternal health physicians

This paper reports the results of focused interviews with child health and maternal health physicians in the public ambulatory care sector of a large Swedish city to describe (1) the organization of their work activities, (2) their perspectives on their work, and (3) their perspectives on the medical care system. Child health physicians (who were attached to a major teaching hospital) practiced in child health clinics for preschoolers and school health clinics. Each physician covered several such settings. Maternal health physicians were attached to local hospitals and practiced full time in maternal health centers. Child health physicians described their work in terms of preventive care, patient care, integration of ambulatory and hospital services, and technological sophistication; they described the system in terms of quality of care, quality of diagnosis and treatment, adequacy of resources, and distribution of services. Maternal health physicians described work in terms of a biophysical orientation, practice independence, relations with hospitals and other specialists, and dependence on nurses; they described the system in terms of technological sophistication, ambulatory and hospital care, and problems of other specialties. Both were more positive about both work and the system than were district general practitioners, and some interpretation is offered.ambulatory care Sweden physicians health care systems

Swedish physicians' perspectives on work and the medical care system: The case of district general practitioners

Interviews with district general practitioners in a large Swedish city in 1978-1979 solicited their perspectives on the frustrations and satisfactions they felt in their work, and on the successes and failures of the Swedish medical care system. With respect to work, four themes emerged: medical routine, patient centered care, overwork and isolation. Five themes emerged with respect to the system: financing, relationships with hospitals and specialists, involvement in political decision making, the size of districts and care centers. These themes are discussed with relation to the influence of the social situation of practice to the influence of the social situation of practice and the conditions for physician satisfaction.ambulatory care Sweden physicians health care systems

Swedish physicians' perspectives on work and the medical care system--III: Private practitioners on the public system

This paper reports the results of focused interviews in 1978-1979 with Swedish physicians in private practice about the public system of medical care in Sweden. They were asked about the system as a work environment for physicians and as a system of care for patients. Respondents, who were outside the public system (although financed mainly by public mechanisms) said the public system as a place to work had advantages in its high technical quality, facilities for research and training, and the capacity to treat complicated disease; its disadvantages were said to be inefficiency, lack of communication, poor patient care, and blocked mobility for physicians without doctorates. As a system of care, its one advantage was said to be that it provided care at less out-of-pocket cost to patients; its reported disadvantages were poor quality care and a tendency to be overly comprehensive. These perspectives are discussed with respect to their structural and historical contexts.ambulatory care Sweden physicians health care systems private practice