Total RNA extracted from both white and gray matter of brain tissue from multiple sclerosis (MS) patients and controls was analyzed using a reverse transcription-polymerase chain reaction for the presence of the nucleic acid of human coronavirus (HCV) 229E and OC43, the two strains characterized to date and associated with respiratory infections. HCV-229E viral RNA was detectable in the central nervous system tissue of 4 of 11 MS patients and in none of 6 neurological and 5 normal controls. No HCV-OC43 nucleic acid was detected in any of the specimens. These results suggest a neurotropism on the part of the 229E strain of human coronavirus and underline the importance of further studies on its tissue distribution. The fact that it was detected only in tissue from MS patients illustrates the need for continued studies on the possible role of coronaviruses in the etiology of MS.

The 299£ prototype strain of human coronavirus (HCV-229£) has so far been mainly associated with infections of the respiratory tract. In the present study, we show evidence for infection of the central nervous system (CNS) by HCV-229E, both in vitro and in vivo. Various human cell lines of CNS origin were tested for their susceptibility to infection by HCV-229£. Production of viral antigens was monitored by indirect immunofluorescence with monoclonal antibodies and infectious progeny virions by plaque assay on the L132 human embryonic lung cell line. The SK-N-SH neuroblastoma and H4 neuroglioma cell lines were highly susceptible to infection. The U-87 MG and U-373 MG astrocytoma cell lines were also infectable by HCV-229E. We could also demonstrate infection of the M03.13 cell line, which was established by fusion of human oligodendrocytes with a thioguanineresistant mutant of the 1E671 (RD) human rhabdomyosarcoma cell line. An apparently more extensive infection of the M03.13 cells, when compared to the parental cells, supports the notion that human oligodendrocytes are differentially susceptible to infection by this virus. We also tested for HCV-229E gene expression in pathological brain specimens. For that purpose, we developed a reverse transcription-polymerase chain reaction (RT-PCR) assay to amplify a portion of the mRNA encoding the viral nucleocapsid protein. Using stringent laboratory conditions, viral RNA was detectable in brain tissue of 4 of 11 multiple sclerosis patients and none of 6 neurological and 5 normal controls. These results strongly suggest neurotropism on the part of HCV-229E and emphasize the importance of further studies on the possible involvement of human coronaviruses in neurological diseases such as multiple sclerosis.

The project revealed both the challenges with situating research within an institution (hierarchy of knowledge, power, and vulnerability) and face-to-face dialogue, as well as positive changes in professional attitudes and consumer empowerment, as providers and patients came to understand what was at stake for each other. The project underscored the need for provider-consumer dialogue as a process to explore tensions and values in promoting recovery-oriented care.

Human coronaviruses (HCV) are important pathogens responsible for respiratory, gastrointestinal and possibly neurological disorders. To better understand the molecular biology of the prototype HCV-229E strain, the nucleotide sequence of the 5'-unique regions of mRNAs 4 and 5 were determined from cloned cDNAs. Sequence analysis of the cDNAs synthesized from mRNA 4 revealed a major difference with previously published results. However, polymerase chain reaction amplification of this region showed that the sequenced cDNAs were produced from minor RNA species, an indication of possible genetic polymorphism in this region of the viral genome. The mutated messenger RNA 4 contains two ORFs: (1) ORF4a consisting of 132 nucleotides which potentially encodes a 44-amino acid polypeptide of 4653 Da; this coding sequence is preceded by a consensus transcriptional initiation sequence, CUAAACU, similar to the ones found upstream of the N and M genes; (2) ORF4b of 249 nucleotides potentially encoding an 83-amino acid basic and leucine-rich polypeptide of 9550 Da. On the other hand, mRNA 5 contains one single ORF of 231 nucleotides which could encode a 77-amino acid basic and leucine-rich polypeptide of 9046 Da. This putative protein presents a significant degree of amino acid homology (33%) with its counterpart found in transmissible gastroenteritis coronavirus (TGEV). The proteins in the two different viruses exhibit similar molecular weights and are extremely hydrophobic. Interestingly, a sequence homology of five amino acids was found between the protein encoded by ORF4b of HCV-229E and an immunologically important region of human myelin basic protein.

BackgroundSince 2007, the Mental Health Commission of Canada has worked collaboratively across all provinces to publish a framework and strategy for recovery and well-being. This federal document is now mandated as policy for implementation between 2012 and 2017. The proposed strategies have been written into provincial health plans, hospital accreditation standards, and annual objectives of psychiatric departments and community organizations. The core premise is: to empower persons with mental illness and their families to become participants in designing their own care, while meeting the needs of a diverse Canadian population. However, recovery principles do not come with an implementation guide to fit the variability of different local contexts. How can policy recommendations and accreditation standards be effectively tailored to support a diversity of stakeholder values? To our knowledge, there is little evidence indicating the most effective manner to accelerate the uptake of recovery-oriented services among providers in a given/particular mental health treatment setting.Methods/DesignThis three-year Canadian Institute of Health Research Partnership in Health System Improvement and The Rx&D Health Research Foundation (HRF) Fostering Canadian Innovation in Research study (2013 to 2017) proposed participatory approaches to implementing recovery principles in a Department of Psychiatry serving a highly diverse Canadian and immigrant population. This project will be conducted in overlapping and recursive phases: I) Conduct formative research to (a) measure the current knowledge and attitudes toward recovery and recovery-oriented practices among service providers, while concurrently (b) exploring the experiential knowledge of recovery service-users and family members; II) Collaborate with service-users and the network-identified opinion leaders among providers to tailor Recovery-in-Action Initiatives to fit the needs and resources of a Department of Psychiatry; and III) Conduct a systematic theory-based evaluation of changes in attitudes and practices within the service-user/service-provider partnership group relative to the overall provider network of the department and identify the barriers and supports within the local context.DiscussionOur anticipated outcome is a participatory toolkit to tailor recovery-oriented services, which will be disseminated to the Mental Health Commission of Canada and Accreditation Canada at the federal level, agencies at the provincial levels, and local knowledge end-users.