Salmonid alphavirus glycoprotein E2 requires low temperature and E1 for virion formation and induction of protective immunity

Salmonid alphavirus (SAV; also known as Salmon pancreas disease virus; family Togaviridae) causes pancreas disease and sleeping disease in Atlantic salmon and rainbow trout, respectively, and poses a major burden to the aquaculture industry. SAV infection in vivo is temperature-restricted and progeny virus is only produced at low temperatures (10–15 °C). Using engineered SAV replicons we show that viral RNA replication is not temperature-restricted suggesting that the viral structural proteins determine low-temperature dependency. The processing/trafficking of SAV glycoproteins E1 and E2 as a function of temperature was investigated via baculovirus vectors in Sf9 insect cells and by transfection of CHSE-214 fish cells with DNA constructs expressing E1 and E2. We identified SAV E2 as the temperature determinant by demonstrating that membrane trafficking and surface expression of E2 occurs only at low temperature and only in the presence of E1. Finally, a vaccination-challenge model in Atlantic salmon demonstrates the biological significance of our findings and shows that SAV replicon DNA vaccines encoding E2 elicit protective immunity only when E1 is co-expressed. This is the first study that identifies E2 as the critical determinant of SAV low-temperature dependent virion formation and defines the prerequisites for induction of a potent immune response in Atlantic salmon by DNA vaccination.     

Hytrosaviridae: a proposal for classification and nomenclature of a new insect virus family

Salivary gland hypertrophy viruses (SGHVs) have been identified from different dipteran species, such as the tsetse fly Glossina pallidipes (GpSGHV), the housefly Musca domestica (MdSGHV) and the narcissus bulbfly Merodon equestris (MeSGHV). These viruses share the following characteristics: (i) they produce non-occluded, enveloped, rod-shaped virions that measure 500–1,000 nm in length and 50–100 nm in diameter; (ii) they possess a large circular double-stranded DNA (dsDNA) genome ranging in size from 120 to 190 kbp and having G + C ratios ranging from 28 to 44%; (iii) they cause overt salivary gland hypertrophy (SGH) symptoms in dipteran adults and partial to complete sterility. The available information on the complete genome sequence of GpSGHV and MdSGHV indicates significant co-linearity between the two viral genomes, whereas no co-linearity was observed with baculoviruses, ascoviruses, entomopoxviruses, iridoviruses and nudiviruses, other large invertebrate DNA viruses. The DNA polymerases encoded by the SGHVs are of the type B and closely related, but they are phylogenetically distant from DNA polymerases encoded by other large dsDNA viruses. The great majority of SGHV ORFs could not be assigned by sequence comparison. Phylogenetic analysis of conserved genes clustered both SGHVs, but distantly from the nudiviruses and baculoviruses. On the basis of the available morphological, (patho)biological, genomic and phylogenetic data, we propose that the two viruses are members of a new virus family named Hytrosaviridae. This proposed family currently comprises two unassigned species, G. pallidipes salivary gland hypertrophy virus and M. domestica salivary gland hypertrophy virus, and a tentative unassigned species, M. equestris salivary gland hypertrophy virus. Here, we present the characteristics and the justification for establishing this new virus family.     

Disability in rheumatoid arthritis after monotherapy with DMARDs

Rheumatoid arthritis (RA) is a progressive disease that leads to an increasing loss of functional ability. Its management should be multidisciplinary, focused primarily at the prevention of functional loss. The aim of the present study was to investigate the effectiveness of monotherapy with disease-modifying antirheumatic drugs (DMARDs) on the prevention of functional loss in RA patients. Of 188 patients with RA, 95 had received DMARD monotherapy (mainly gold salts, but also antimalarials and sulfasalazin) for at least 36 months; 93 patients had not received DMARDs because of their inability to attend the rheumatology clinic regularly because of accessibility difficulties. All 188 patients were examined at the start of the follow-up and at its completion, some 42 months later. The following parameters were determined at the two examinations: tenderness and pain in individual joints, functional independence, functional and working status, and the results of ancillary tests. At the end of the follow-up there was a decrease in functional independence and deterioriation in the functional and working status in both groups. Long-term monotherapy with DMARDs had not prevented functional loss or the ensuing disability in RA patients.     

Conservative therapy in painful shoulder syndrome

Shoulder pain is a common complain, estimates of the annual incidence in general practice very from 7 to 25 cases per 1000 patients. Monoarticular involvement of shoulder does occur. Pain is the major complaint and is aggravated by movement, followed by decreased range of motion and functional capacity. There may be concomitant gross swelling about the shoulder as result of synovial inflammation and sub-deltoid or scapulothoracic bursitis. Physical therapy modalities, as conservative treatment, is the best way to help ameliorate some symptoms and prevent disability.     

Effect of rheumatoid arthritis on physical performance of patients

To determine the changes occurRing in physical performance of patients with RA, 188 patients have been observed over a ten-year period. The observation included two groups: the test group comprising 93 patients with RA who have never been treated by any disease-modifying antirheumatic drugs (DMARDs) and the control group comprising 95 patients with RA who have regularly taken DMARDs under the rheumatologist's supervision. The average age of the test group was considerably higher, there were more retired persons with a prolonged course of illness, their physical performance being more intensely affected than that of the control group. Further analysis during the observation period showed significant decrease of physical performance in both groups regardless of their being treated or not by the DMARDs which, in our opinion, only modify the illness. To conclude, irrespective of the application of the DMARDs, RA is undoubtedly an illness with considerable socio-economic significance since it leads to great physical disability (invalidity) of all RA patients.