Elucidating the Role of the Complement Control Protein in Monkeypox Pathogenicity

Monkeypox virus (MPXV) causes a smallpox-like disease in humans. Clinical and epidemiological studies provide evidence of pathogenicity differences between two geographically distinct monkeypox virus clades: the West African and Congo Basin. Genomic analysis of strains from both clades identified a ∼10 kbp deletion in the less virulent West African isolates sequenced to date. One absent open reading frame encodes the monkeypox virus homologue of the complement control protein (CCP). This modulatory protein prevents the initiation of both the classical and alternative pathways of complement activation. In monkeypox virus, CCP, also known as MOPICE, is a ∼24 kDa secretory protein with sequence homology to this superfamily of proteins. Here we investigate CCP expression and its role in monkeypox virulence and pathogenesis. CCP was incorporated into the West African strain and removed from the Congo Basin strain by homologous recombination. CCP expression phenotypes were confirmed for both wild type and recombinant monkeypox viruses and CCP activity was confirmed using a C4b binding assay. To characterize the disease, prairie dogs were intranasally infected and disease progression was monitored for 30 days. Removal of CCP from the Congo Basin strain reduced monkeypox disease morbidity and mortality, but did not significantly decrease viral load. The inclusion of CCP in the West African strain produced changes in disease manifestation, but had no apparent effect on disease-associated mortality. This study identifies CCP as an important immuno-modulatory protein in monkeypox pathogenesis but not solely responsible for the increased virulence seen within the Congo Basin clade of monkeypox virus

Comparison of Osteopathic and Allopathic Medical Schools' Support for Primary Care

OBJECTIVE: To contrast prevailing behaviors and attitudes relative to primary care education and practice in osteopathic and allopathic medical schools. DESIGN: Descriptive study using confidential telephone interviews conducted in 1993–94. Analyses compared responses of osteopaths and allopaths, controlling for primary care orientation. SETTING: United States academic health centers. PARTICIPANTS: National stratified probability samples of first-year and fourth-year medical students, postgraduate year 2 residents, and clinical faculty in osteopathic and allopathic medical schools, a sample of allopathic deans, and a census of deans of osteopathic schools (n =457 osteopaths; n =2,045 allopaths). MEASUREMENTS: Survey items assessed personal characteristics, students' reasons for entering medicine, learners' primary care educational experiences, community support for primary care, and attitudes toward the clinical and academic competence of primary care physicians. MAIN RESULTS: Primary care physicians composed a larger fraction of the faculty in osteopathic schools than in allopathic schools. Members of the osteopathic community were significantly more likely than their allopathic peers to describe themselves as socioemotionally oriented rather than technoscientifically oriented. Osteopathic learners were more likely than allopathic learners to have educational experiences in primary care venues and with primary care faculty, and to receive encouragement from faculty, including specialists, to enter primary care. Attitudes toward the clinical and academic competence of primary care physicians were consistently negative in both communities. Differences between communities were sustained after controlling for primary care orientation. CONCLUSIONS: In comparison with allopathic schools, the cultural practices and educational structures in osteopathic medical schools better support the production of primary care physicians. However, there is a lack of alignment between attitudes and practices in the osteopathic community