Abstract
Part of the Togaviridae family, alphaviruses, including chikungunya virus (CHIKV), Sindbis virus (SINV) and Ross River virus (RRV), are able to cause significant inflammatory pathologies ranging from arthritis to encephalitis. Following symptomatic infection with arthritis-associated alphaviruses, patients often experience severe joint pain, affecting distal and small joints, which can last six months or longer. Recently, methotrexate (MTX), a disease modifying anti-rheumatic drug (DMARD), was used to treat patients experiencing chronic rheumatic symptoms following infection with CHIKV. Here, the effect of MTX on Ross River virus disease (RRVD) in mice was examined to better understand its therapeutic potential for alphaviral-induced musculoskeletal disease and to further our knowledge of the development of alphaviral pathologies. Using a mouse model, we analyzed the effect of MTX on RRVD. RRV disease pathogenesis in response to MTX treatment was determined by measuring levels of proinflammatory factors, cellular infiltrates, viral titer and histological analysis of infected tissues. RRV-infected mice receiving MTX treatment rapidly developed musculoskeletal disease, which correlated with a significant influx of inflammatory cell infiltrates into the skeletal muscle tissue. Although no difference was observed in the level of proinflammatory cytokines and chemokines, the viral load increased at early time points post infection in the serum and quadriceps of MTX treated mice, possibly contributing to disease pathogenesis. Results suggest that MTX treatment of acute RRVD in mice provides no therapeutic benefit and underline the importance of inflammatory monocytes in alphaviral induced arthritides.
Highlights
Arthropod-borne alphaviruses are globally widespread and capable of causing significant inflammatory pathologies
Mice 21-day-old C57BL/6 mice were subcutaneously inoculated in the thorax with 104 plaque-forming units (PFU) of River virus (RRV) diluted in phosphate buffered saline (PBS) in a 50 ml volume
MTX Treatment Accelerates River virus disease (RRVD) Onset in Mice To analyze the effect of MTX on RRVD, mice were infected with 104 PFU of RRV and received daily IP injections of MTX or PBS control commencing on the day of infection
Summary
Arthropod-borne alphaviruses are globally widespread and capable of causing significant inflammatory pathologies. Outbreaks of Old World alphaviruses, such as chikungunya virus (CHIKV), Sindbis virus (SINV) and Ross River virus (RRV), are largely associated with highly debilitating arthritic symptoms, causing significant human morbidity. RRV is endemic to Australia and Papua New Guinea where it is responsible for increasingly frequent outbreaks of polyarthritis/ arthralgia. In 2009, 4,786 cases of Ross River virus disease (RRVD) were reported in Australia [1]. In Western Australia the number of cases of RRV reported in January and February, rose from 245 in 2011 to 632 for the same period in 2012 [2]. The severe chronic and recurrent arthralgia experienced by infected patients, together with the epidemic nature of RRV outbreaks, makes RRVD an illness of major socioeconomic concern [4]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
