An Animal Model for Studying the Pathogenesis of Chikungunya Virus Infection

Abstract

Newborn and 14-day-old mice inoculated subcutaneously with chikungunya virus (CHIKV) developed lethargy, difficulty walking, dragging of hind limbs, and reduced weight gain within 7-10 days after infection (PI). During the initial 6-7 days PI, the animals had viremia; high levels (10(6)-10(8) PFU) of CHIKV were also present in leg muscle. The virus persisted in muscle for several days after viremia disappeared. The major histopathologic changes were in skeletal muscle, which were focal necrosis and inflammation, followed by fibrosis and dystrophic calcification. Some mice also showed dystrophic calcification in the joint cartilage, but there were few deaths, and most of the animals eventually recovered. CHIKV antigen was shown by immunohistochemistry in the muscle for several weeks after infection. Based on the clinical and pathologic similarities with CHIKV infection in humans, young ICR and CD-1 mice offer a useful and realistic model for further study of the pathogenesis and treatment of CHIKV infection.

Chikungunya: an emerging and spreading arthropod-borne viral disease.

“…Moreover, it was shown in a mouse model, as well as in humans, that the fibroblast is the major cell type targeted in vivo by CHIKV. This observation confirms previous in vitro findings [27], and accounts for CHIKV tropism for muscles, joint and skin connective tissues [29].…”

“…Recently, a mouse model for Chikungunya infection was developed, suggesting that CHIKV-induced arthritis is of immunopathological origin [30,29] and that the severity of CHIKV infection is critically dependent on two host factors: age and functionality of the type-I Interferon (INF) signaling system [29]. Whereas it is clear that an increased neonatal susceptibility is also observed in humans [31,32], the relevance of a role for type-I INF in severe CHIKV infection in adult humans remains to be demonstrated.…”

Arthrogenic Alphaviruses and Inflammatory Myopathies

“…Neonatal C57BL/6 inbred mice and CD-1 outbred mice were found to be susceptible to CHIKV infection, showing an age-dependent disease severity with a model established in 14-dayold mice (Couderc et al, 2008;Morrison et al, 2011;Ziegler et al, 2008). These models show extensive myositis in the skeletal muscle at 7-10 days p.i.…”

A Mouse Model of Chikungunya Virus–Induced Musculoskeletal Inflammatory Disease

“…19 Although CHIKV was detected in muscle and joint tissue in these mice, the pathological outcomes in these tissues were not addressed, 19 and these models may be more relevant for studying the pathogenesis of atypical CHIKV disease. Ziegler et al 20 described severe skeletal muscle necrosis and inflammation after CHIKV infection of outbred strains of mice. These studies were promising; however, whether infected mice developed other musculoskeletal conditions, such as arthritis, was not reported.…”