Comparative Pathogenesis of Epidemic and Enzootic Chikungunya Viruses in a Pregnant Rhesus Macaque Model

Chen, Ching-I; Clark, David; Pesavento, Patricia A.; Lerche, Nicholas W.; Luciw, Paul A.; Reisen, William K.; Brault, Aaron C.

doi:10.4269/ajtmh.2010.10-0290

Cited by 67 publications

(71 citation statements)

References 43 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data are consistent with epidemiological studies which have documented the development of protracted disease symptoms during outbreaks of CHIKV in humans involving any of the three CHIKV genotypes (5). The detection of CHIKV RNA in joint-associated tissues is also consistent with previous studies in humans in which CHIKV antigen was detected in synovial biopsy specimens collected from a patient with chronic disease (12) and in experimentally inoculated rhesus and cynomolgous macaques in which CHIKV RNA was detected in joints at later times postinoculation (22,50). Analogously, Ross River virus RNA has been detected in knee biopsy specimens collected from patients 5 weeks after the onset of joint symptoms (51).…”

Section: Discussionsupporting

confidence: 90%

Chronic Joint Disease Caused by Persistent Chikungunya Virus Infection Is Controlled by the Adaptive Immune Response

Hawman

Stoermer

Montgomery

et al. 2013

J Virol

208

224

View full text Add to dashboard Cite

f Chikungunya virus (CHIKV) is a reemerging mosquito-borne pathogen that causes incapacitating disease in humans characterized by intense joint pain that can persist for weeks, months, or even years. Although there is some evidence of persistent CHIKV infection in humans suffering from chronic rheumatologic disease symptoms, little is known about chronic disease pathogenesis, and no specific therapies exist for acute or chronic CHIKV disease. To investigate mechanisms of chronic CHIKV-induced disease, we utilized a mouse model and defined the duration of CHIKV infection in tissues and the associated histopathological changes. Although CHIKV RNA was readily detectable in a variety of tissues very early after infection, CHIKV RNA persisted specifically in joint-associated tissues for at least 16 weeks. Inoculation of Rag1 ؊/؊ mice, which lack T and B cells, resulted in higher viral levels in a variety of tissues, suggesting that adaptive immunity controls the tissue specificity and persistence of CHIKV infection. The presence of CHIKV RNA in tissues of wild-type and Rag1 ؊/؊ mice was associated with histopathological evidence of synovitis, arthritis, and tendonitis; thus, CHIKV-induced persistent arthritis is not mediated primarily by adaptive immune responses. Finally, we show that prophylactic administration of CHIKV-specific monoclonal antibodies prevented the establishment of CHIKV persistence, whereas therapeutic administration had tissue-specific efficacy. These findings suggest that chronic musculoskeletal tissue pathology is caused by persistent CHIKV infection and controlled by adaptive immune responses. Our results have significant implications for the development of strategies to mitigate the disease burden associated with CHIKV infection in humans.

show abstract

Section: Discussionsupporting

confidence: 90%

Chronic Joint Disease Caused by Persistent Chikungunya Virus Infection Is Controlled by the Adaptive Immune Response

Hawman

Stoermer

Montgomery

et al. 2013

J Virol

208

224

View full text Add to dashboard Cite

show abstract

“…Previous to this study, direct infection of myofibers by CHIKV had not been shown, though evidence of myofiber fragmentation and necrosis has been reported (33). Since we observed the infection of myofibers following i.d.…”

Section: Discussionmentioning

confidence: 50%

“…Neonatal mice infected with the La Reunion recombinant strain (LR2006 OPY1) developed more severe disease, with progressive hind limb weakness and severe myonecrosis, than those infected with the Senegal strain (37997). 37997 and another strain from the 2006 outbreak (DHS-4263) were also compared in a macaque model, where slightly elevated viremia was seen with the 37997 strain (33). Mild muscle fiber necrosis was also seen in several animals, but muscle titers or pathology during acute infection was not determined (33).…”

Section: Discussionmentioning

confidence: 99%

“…37997 and another strain from the 2006 outbreak (DHS-4263) were also compared in a macaque model, where slightly elevated viremia was seen with the 37997 strain (33). Mild muscle fiber necrosis was also seen in several animals, but muscle titers or pathology during acute infection was not determined (33). In the murine arthritis model, more severe joint swelling was seen in mice infected with the LR2006 OPY1 strain than in those infected with an Asian isolate from the 1960s (34).…”

Section: Discussionmentioning

confidence: 99%

“…Previous work has shown that CHIKV replicates in the connective tissue fibroblasts and myoblasts in both mice and humans (16). While other studies have noted myofiber necrosis and attributed this to infection of those fibers by CHIKV, previous studies have not detected infection of the myofibers (33). We utilized recombinant CHIKV strains in which GFP expression was driven by a subgenomic promoter in either the 37997 or LR2006 OPY1 backbone.…”

Section: Chikv Strains 37997 and Lr2006 Opy1 Display Similar Growth Amentioning

confidence: 99%

See 2 more Smart Citations

Infection of Myofibers Contributes to Increased Pathogenicity during Infection with an Epidemic Strain of Chikungunya Virus

Rohatgi

Corbo

Monte

et al. 2014

J Virol

View full text Add to dashboard Cite

Chikungunya virus (CHIKV) is an alphavirus transmitted by mosquitoes that is known to cause severe arthritis and myositis in affected patients. The ongoing epidemic began in eastern Africa in 2004 and then spread to islands of the Indian Ocean, India, and Southeast Asia, ultimately afflicting millions. During this outbreak, more severe disease manifestations, including fatalities, have been documented. The reasons for this change in pathogenesis are multifactorial but likely include mutations that have arisen in the viral genome which could alter disease pathogenesis. To test this hypothesis, we used a murine model of CHIKV to compare the disease pathogeneses of two recombinant strains of CHIKV, the first derived from the La Reunion outbreak in 2006 (LR2006 OPY1) and the second isolated from Senegal in 1983 (37997). While the two strains exhibited similar growth in mammalian cells in vitro, we observed more severe clinical disease and pathology in mice infected with the LR2006 OPY1 strain of CHIKV, which included prolonged viremia and elevated viral titers and persistence in the muscle, resulting in devastating myonecrosis. Both CHIKV strains infected connective tissue fibroblasts of the muscle, but only the LR2006 OPY1 strain replicated within myofibers in vivo, despite similar growth of the two strains in these cell types in vitro. However, when the 37997 strain was administered directly into muscle, myofiber infection was comparable to that in LR2006 OPY1-infected mice. These results indicate that differences in the ability of the strain of CHIKV to establish infection in myofibers may contribute to the increased disease severity. IMPORTANCECHIKV is an emerging pathogen that causes significant morbidity. Little is known about the pathogenesis of the disease, and this study suggests that the ability of a recent epidemic strain to infect myofibers results in increased disease severity. Better understanding of how CHIKV causes disease contributes to the ultimate goal of creating therapeutics to alleviate the impact of this debilitating virus.

show abstract

Dengue, Japanese encephalitis and Chikungunya virus antibody prevalence among captive monkey (Macaca nemestrina) colonies of Northern Thailand

Nakgoi

Nitatpattana

Wajjwalku

et al. 2013

American J Primatol

View full text Add to dashboard Cite

The potential of macaque Macaca nemestrina leonina in Thailand to be infected by endemic arboviruses was assessed. The prevalence of antibodies of three arboviruses actively circulating in Thailand was determined by Plaque Reduction Neutralization assay procedures using samples from captive colonies in Northern Thailand. Out of 38 macaques, 9 (24%) presented reacting antibodies against dengue virus, 5 (13%) against Japanese encephalitis virus, and 4 (10%) against Chikungunya virus. Our results indicate that the northern pig-tailed macaque in Thailand can be infected by these arboviruses, inferring therefore that their virus specific vectors have bitten them. Given that, northern pig-tailed macaque represents an abundant population, living in close range to human or in peridomestic setting, they could play a role as potential reservoir host for arboviruses circulating in Thailand.

show abstract

Comparative Pathogenesis of Epidemic and Enzootic Chikungunya Viruses in a Pregnant Rhesus Macaque Model

Cited by 67 publications

References 43 publications

Chronic Joint Disease Caused by Persistent Chikungunya Virus Infection Is Controlled by the Adaptive Immune Response

Chronic Joint Disease Caused by Persistent Chikungunya Virus Infection Is Controlled by the Adaptive Immune Response

Infection of Myofibers Contributes to Increased Pathogenicity during Infection with an Epidemic Strain of Chikungunya Virus

Dengue, Japanese encephalitis and Chikungunya virus antibody prevalence among captive monkey (Macaca nemestrina) colonies of Northern Thailand

Contact Info

Product

Resources

About