scholarly journals A Mouse Model for Studying Post-Acute Arthritis of Chikungunya

2021 ◽  
Vol 9 (9) ◽  
pp. 1998
Author(s):  
Aileen Y. Chang ◽  
Sarah R. Tritsch ◽  
Abigail J. Porzucek ◽  
Arnold M. Schwartz ◽  
Margaux Seyler-Schmidt ◽  
...  
Keyword(s):  
Mouse Model ◽  
Mouse Models ◽  
Targeted Therapies ◽  
Scoring System ◽  
Chikungunya Virus ◽  
Evidence Based ◽  
Novel Therapies ◽  
Wild Type ◽  
Chikv Infection ◽  
Acute Arthritis

Chikungunya virus (CHIKV) was introduced to the Americas in 2013, causing two million infections across over thirty countries. CHIKV causes a chronic debilitating arthritis in one fourth of infected individuals and currently evidence-based targeted therapies for the treatment of CHIKV arthritis are lacking. Multiple mouse models of chikungunya have been developed to study acute CHIKV infection. In humans, post-CHIKV arthritis may persist for months to years after viremia from a CHIKV infection has resolved. Therefore, the development of a mouse model of post-acute arthritis of chikungunya may facilitate the study of potential novel therapeutics for this arthritis. In this article we describe the development of a wild-type immunocompetent C57BL/6 mouse model for post-acute arthritis of chikungunya, including a histologic inflammation scoring system, as well as suggestions for how this mouse model may be used to examine the efficacy of novel therapies for CHIKV arthritis.

scholarly journals Effects of Chikungunya virus immunity on Mayaro virus disease and epidemic potential

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Emily M. Webb ◽  
Sasha R. Azar ◽  
Sherry L. Haller ◽  
Rose M. Langsjoen ◽  
Candace E. Cuthbert ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Chikungunya Virus ◽  
Semliki Forest Virus ◽  
Virus Disease ◽  
Cross Protection ◽  
Health Concern ◽  
Antigenic Relationship ◽  
Wild Type ◽  
Chikv Infection ◽  
Mayaro Virus

AbstractMayaro virus (MAYV) causes an acute febrile illness similar to that produced by chikungunya virus (CHIKV), an evolutionary relative in the Semliki Forest virus complex of alphaviruses. MAYV emergence is typically sporadic, but recent isolations and outbreaks indicate that the virus remains a public health concern. Given the close phylogenetic and antigenic relationship between CHIKV and MAYV, and widespread distribution of CHIKV, we hypothesized that prior CHIKV immunity may affect MAYV pathogenesis and/or influence its emergence potential. We pre-exposed immunocompetent C57BL/6 and immunocompromised A129 or IFNAR mice to wild-type CHIKV, two CHIKV vaccines, or a live-attenuated MAYV vaccine, and challenged with MAYV. We observed strong cross-protection against MAYV for mice pre-exposed to wild-type CHIKV, and moderately but significantly reduced cross-protection from CHIKV-vaccinated animals. Immunity to other alphavirus or flavivirus controls provided no protection against MAYV disease or viremia. Mechanistic studies suggested that neutralizing antibodies alone can mediate this protection, with T-cells having no significant effect on diminishing disease. Finally, human sera obtained from naturally acquired CHIKV infection cross-neutralized MAYV at high titers in vitro. Altogether, our data suggest that CHIKV infection can confer cross-protective effects against MAYV, and the resultant reduction in viremia may limit the emergence potential of MAYV.

scholarly journals Interferon Response Factors 3 and 7 Protect against Chikungunya Virus Hemorrhagic Fever and Shock

2012 ◽  
Vol 86 (18) ◽  
pp. 9888-9898 ◽  
Author(s):  
Penny A. Rudd ◽  
Jane Wilson ◽  
Joy Gardner ◽  
Thibaut Larcher ◽  
Candice Babarit ◽  
...  
Keyword(s):  
Chikungunya Virus ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Interferon Response ◽  
Wild Type ◽  
Chikv Infection ◽  
Response Factors ◽  
Adult Mice

Chikungunya virus (CHIKV) infections can produce severe disease and mortality. Here we show that CHIKV infection of adult mice deficient in interferon response factors 3 and 7 (IRF3/7−/−) is lethal. Mortality was associated with undetectable levels of alpha/beta interferon (IFN-α/β) in serum, ∼50- and ∼10-fold increases in levels of IFN-γ and tumor necrosis factor (TNF), respectively, increased virus replication, edema, vasculitis, hemorrhage, fever followed by hypothermia, oliguria, thrombocytopenia, and raised hematocrits. These features are consistent with hemorrhagic shock and were also evident in infected IFN-α/β receptor-deficient mice.In situhybridization suggested CHIKV infection of endothelium, fibroblasts, skeletal muscle, mononuclear cells, chondrocytes, and keratinocytes in IRF3/7−/−mice; all but the latter two stained positive in wild-type mice. Vaccination protected IRF3/7−/−mice, suggesting that defective antibody responses were not responsible for mortality. IPS-1- and TRIF-dependent pathways were primarily responsible for IFN-α/β induction, with IRF7 being upregulated >100-fold in infected wild-type mice. These studies suggest that inadequate IFN-α/β responses following virus infection can be sufficient to induce hemorrhagic fever and shock, a finding with implications for understanding severe CHIKV disease and dengue hemorrhagic fever/dengue shock syndrome.

scholarly journals Chikungunya Virus Arthritis in Adult Wild-Type Mice

2010 ◽  
Vol 84 (16) ◽  
pp. 8021-8032 ◽  
Author(s):  
Joy Gardner ◽  
Itaru Anraku ◽  
Thuy T. Le ◽  
Thibaut Larcher ◽  
Lee Major ◽  
...  
Keyword(s):  
Mouse Model ◽  
Rheumatic Disease ◽  
Chikungunya Virus ◽  
Virus Disease ◽  
Ross River Virus ◽  
Reunion Island ◽  
Wild Type ◽  
Primary Mouse ◽  
Réunion Island ◽  
Asian Isolate

ABSTRACT Chikungunya virus is a mosquito-borne arthrogenic alphavirus that has recently reemerged to produce the largest epidemic ever documented for this virus. Here we describe a new adult wild-type mouse model of chikungunya virus arthritis, which recapitulates the self-limiting arthritis, tenosynovitis, and myositis seen in humans. Rheumatic disease was associated with a prolific infiltrate of monocytes, macrophages, and NK cells and the production of monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ). Infection with a virus isolate from the recent Reunion Island epidemic induced significantly more mononuclear infiltrates, proinflammatory mediators, and foot swelling than did an Asian isolate from the 1960s. Primary mouse macrophages were shown to be productively infected with chikungunya virus; however, the depletion of macrophages ameliorated rheumatic disease and prolonged the viremia. Only 1 μg of an unadjuvanted, inactivated, whole-virus vaccine derived from the Asian isolate completely protected against viremia and arthritis induced by the Reunion Island isolate, illustrating that protection is not strain specific and that low levels of immunity are sufficient to mediate protection. IFN-α treatment was able to prevent arthritis only if given before infection, suggesting that IFN-α is not a viable therapy. Prior infection with Ross River virus, a related arthrogenic alphavirus, and anti-Ross River virus antibodies protected mice against chikungunya virus disease, suggesting that individuals previously exposed to Ross River virus should be protected from chikungunya virus disease. This new mouse model of chikungunya virus disease thus provides insights into pathogenesis and a simple and convenient system to test potential new interventions.

scholarly journals γδ T Cells Play a Protective Role in Chikungunya Virus-Induced Disease

2015 ◽  
Vol 90 (1) ◽  
pp. 433-443 ◽  
Author(s):  
Kristin M. Long ◽  
Martin T. Ferris ◽  
Alan C. Whitmore ◽  
Stephanie A. Montgomery ◽  
Lance R. Thurlow ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chikungunya Virus ◽  
Joint Damage ◽  
Γδ T Cells ◽  
The United States ◽  
Protective Role ◽  
Γδ T Cell ◽  
Wild Type ◽  
Chikv Infection

ABSTRACTChikungunya virus (CHIKV) is an alphavirus responsible for causing epidemic outbreaks of polyarthralgia in humans. Because CHIKV is initially introduced via the skin, where γδ T cells are prevalent, we evaluated the response of these cells to CHIKV infection. CHIKV infection led to a significant increase in γδ T cells in the infected foot and draining lymph node that was associated with the production of proinflammatory cytokines and chemokines in C57BL/6J mice. γδ T cell−/−mice demonstrated exacerbated CHIKV disease characterized by less weight gain and greater foot swelling than occurred in wild-type mice, as well as a transient increase in monocytes and altered cytokine/chemokine expression in the foot. Histologically, γδ T cell−/−mice had increased inflammation-mediated oxidative damage in the ipsilateral foot and ankle joint compared to wild-type mice which was independent of differences in CHIKV replication. These results suggest that γδ T cells play a protective role in limiting the CHIKV-induced inflammatory response and subsequent tissue and joint damage.IMPORTANCERecent epidemics, including the 2004 to 2007 outbreak and the spread of CHIKV to naive populations in the Caribbean and Central and South America with resultant cases imported into the United States, have highlighted the capacity of CHIKV to cause explosive epidemics where the virus can spread to millions of people and rapidly move into new areas. These studies identified γδ T cells as important to both recruitment of key inflammatory cell populations and dampening the tissue injury due to oxidative stress. Given the importance of these cells in the early response to CHIKV, this information may inform the development of CHIKV vaccines and therapeutics.

scholarly journals DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for Alagille syndrome

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Simona Hankeova ◽  
Jakub Salplachta ◽  
Tomas Zikmund ◽  
Michaela Kavkova ◽  
Noémi Van Hul ◽  
...  
Keyword(s):  
Bile Duct ◽  
Mouse Model ◽  
Mouse Models ◽  
New Technology ◽  
Intrahepatic Bile Duct ◽  
Alagille Syndrome ◽  
3D Analysis ◽  
Wild Type ◽  
Organ Function ◽  
Proof Of Principle

Organ function depends on tissues adopting the correct architecture. However, insights into organ architecture are currently hampered by an absence of standardized quantitative 3D analysis. We aimed to develop a robust technology to visualize, digitalize, and segment the architecture of two tubular systems in 3D: double resin casting micro computed tomography (DUCT). As proof of principle, we applied DUCT to a mouse model for Alagille syndrome (Jag1Ndr/Ndr mice), characterized by intrahepatic bile duct paucity, that can spontaneously generate a biliary system in adulthood. DUCT identified increased central biliary branching and peripheral bile duct tortuosity as two compensatory processes occurring in distinct regions of Jag1Ndr/Ndr liver, leading to full reconstitution of wild-type biliary volume and phenotypic recovery. DUCT is thus a powerful new technology for 3D analysis, which can reveal novel phenotypes and provide a standardized method of defining liver architecture in mouse models.

Sign in / Sign up

Export Citation Format

Share Document