Chikungunya virus (CHIKV) is an arthropod-borne virus (arbovirus) primarily transmitted to humans through the bite of infected Aedes mosquitoes, particularly Aedes aegypti and Aedes albopictus. CHIKV causes Chikungunya fever, characterized by fever, joint pain, and rash. The virus has a single-stranded RNA genome with a positive-sense polarity. Its structure consists of a lipid membrane surrounding a nucleocapsid, with two main viral proteins: E1 and E2, which facilitate viral entry into host cells. CHIKV primarily affects tropical and subtropical regions, causing periodic outbreaks. The virus is of significant public health concern due to its widespread transmission and long-lasting joint symptoms in affected individuals.
CHIKV exhibits broad tropism, replicating in various vertebrate and invertebrate cells. It utilizes glycosaminoglycans as attachment factors, facilitating its entry into host cells. After attachment via the E2 protein, CHIKV enters cells through endocytosis. Endosomal acidification induces conformational changes of viral glycoproteins, enabling fusion of viral envelope with the endosomal membrane. After the viral genome is released into the cytoplasm, it is translated into nonstructural polyproteins, forming the viral replicase that synthesizes negative-sense viral RNA for replication.
Fig. 1 CHIKV cell entry and replication.1, 3
CHIKV enters the body via a mosquito bite and begins replicating at the inoculation site in fibroblasts and potentially in macrophages. Although the virus activates innate immune responses, it spreads through the lymphatic system into the bloodstream, facilitating its distribution to various tissues such as lymphoid organs, skin, muscles, joints, tendons, and, in severe cases, the brain and liver. High viral loads in the serum (>109 virus particles/ml) result from replication in peripheral tissues. This viremia facilitates easy transmission to mosquitoes, aiding in the spread of the virus. Joint inflammation and pain are common symptoms due to viral replication in synovial tissues.
CHIKV triggers a strong innate immune response upon infection. IFNs are rapidly produced, crucial in inhibiting viral replication. Additionally, proinflammatory chemokines, cytokines, and growth factors are released, contributing to local inflammation. CHIKV infection causes direct cellular damage, particularly in tissues like joints, which leads to pain and swelling. CHIKV infects monocytes and macrophages, which contribute to the virus-induced disease processes in both humans and animals. CD4+ T cells act as inflammatory mediators in infected tissues but also aid in viral clearance. Tregs reduce CHIKV disease by suppressing CHIKV-specific CD4+ effector T cells. Additionally, γδ T cells, abundant in skin, protect against CHIKV, as their deficiency worsens infection. These immune mechanisms, although essential for controlling the virus, also contribute to the prolonged inflammation and joint pathology observed in CHIKV-infected individuals.
Fig. 2 Summary of the roles of each T cell subset during acute CHIKV infection.2, 3
Neutralizing antibody is crucial for controlling CHIKV viremia. Infected humans, mice, and non-human primates develop strong neutralizing IgM and IgG antibodies that effectively control the virus and provide cross-protection against reinfection. IgM appears within 5-7 days of symptoms, peaks several weeks later, and declines over months, while IgG levels rise around 7-10 days post-symptom onset, often after viremia clears. Potent neutralizing antibodies bind to E2 glycoprotein A and B domains, with domain B antibodies offering broad protection against various CHIKV strains. Monoclonal antibodies, used as prophylactics or therapeutics, also provide protection, even in post-exposure scenarios.
Fig. 3 Profile of neutralizing MAbs against CHIKV.4
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Anti-CHIKV Neutralizing Antibody (V3S-0522-YC6849) (CAT#: V3S-0522-YC6849)
Target: CHIKV
Host Species: Human
Target Species: Chikungunya virus (CHIKV),
Application: ELISA,Neut,
Mouse Anti-CHIKV Neutralizing Antibody (V3S-0723-FY125) (CAT#: V3S-0723-FY125)
Target: CHIKV
Host Species: Mouse
Target Species: Chikungunya virus (CHIKV),
Application: ELISA,WB,Neut,