Molecular Mechanisms Involved in the Pathogenesis of Alphavirus-Induced Arthritis

Abstract

Arthritogenic alphaviruses, including Ross River virus (RRV), Chikungunya virus (CHIKV), Sindbis virus (SINV), Mayaro virus (MAYV), O'nyong-nyong virus (ONNV), and Barmah Forest virus (BFV), cause incapacitating and long lasting articular disease/myalgia. Outbreaks of viral arthritis and the global distribution of these diseases point to the emergence of arthritogenic alphaviruses as an important public health problem. This review discusses the molecular mechanisms involved in alphavirus-induced arthritis, exploring the recent data obtained with in vitro systems and in vivo studies using animal models and samples from patients. The factors associated to the extension and persistence of symptoms are highlighted, focusing on (a) virus replication in target cells, and tissues, including macrophages and muscle cells; (b) the inflammatory and immune responses with recruitment and activation of macrophage, NK cells and T lymphocytes to the lesion focus and the increase of inflammatory mediators levels; and (c) the persistence of virus or viral products in joint and muscle tissues. We also discuss the importance of the establishment of novel animal models to test new molecular targets and to develop more efficient and selective drugs to treat these diseases.

Chikungunya virus: epidemiology, replication, disease mechanisms, and prospective intervention strategies

“…CHIKV-induced disease shares many similarities with illnesses caused by other arthritogenic alphaviruses, with some distinctions observed (reviewed in refs. [101][102][103]. After deposition into the bloodstream or skin through a bite of an infected mosquito, CHIKV replicates at the site of inoculation in fibroblasts and possibly macrophages ( Figure 3 and refs.…”

Chikungunya

“…Different joint manifestations during different phases of Chikungunya fever have been described in the literature, including arthralgia, inflammatory arthritis, synovitis, enthesitis, tenosynovitis, and bursitis. 41 Experimental models of arthritis induced by alpha viruses suggest that the pathogenesis is the result of a combination of direct tissue and cell damage caused by viral replication and indirect immune activation responses in the target tissues 42 . Different cytokines, chemokines, and other inflammatory mediators are produced; these are related to the intensity of inflammation in the acute phase; are involved in the recruitment of macrophages, natural killer cells, and T lymphocytes to the site of viral replication; and cause dysregulation of inflammation in this stage, leading to the expression of other inflammatory proteins responsible for damaging the joint in the chronic phase.…”

“…The presence of immunoglobulin M (IgM) antibodies detected months after the acute infection suggests persistence of the virus or its antigens; this may perpetuate the inflammatory process in the joints. 41,44 In an outbreak in Italy, Moro et al reported that IgM was detected in 52% (131/249) of patients within 5 months of the contracting disease and in 13. 2% (30/227) with 12 months of disease evolution 42 .…”

“…These HLA polymorphisms may be involved in the pathogenesis of the disease. 41,42 A sub-group of patients present with neuropathic-type pain. 45 Neuropathic pain syndromes are caused by lesions in or dysfunction of the nervous system; …”

Chikungunya congénito y neonatal: Problemas emergentes en pediatría en Latinoamérica

“…Su patogénesis molecular puede generar un desenlace crónico (5) independiente de los antecedentes del paciente y generando un impacto social considerando la (6) discapacidad que se genera .…”