3 Virus Receptor and Host Factors

Infection of CHIKV requires for the synergism of adhesion factors and cellular receptors. Virus receptors are located on the surface of host cells. Specific-binding with virions mediates internalization and induces infection. MXRA8 is the key receptor of various alphaviruses(e.g. CHIKV, MAYV, RRV, ONNV, SFV). MXRA8 can interact with E2 and E1 protein respectively. In vitro and vivo experiments show blocking or knock-out of MXRA8 can obviously decrease level of virus infection. Other potential receptors like CD147 and PHB1 still require for further research. It’s also found that heparan sulfate and phosphatidylserine receptor proteins can increase the adhesion and infection ability of CHIKV.

Besides, some host factors help virus invasion or replication. FHL1A is the host factor required for replication and pathopoiesis, and interacts with hypervariable region of nsP3, mainly expressed in cytoplasm of striated muscle and fibroblasts. DHX9 is involved in the translation process of non-structural protein via regulating CHIKV RNA synthesis. The efficient replication of CHIKV genome also depends on chloride channels of human and mosquito cells.

4 Research Model

CHIKV is the zoonotic virus infecting human beings and non-human beings(e.g. rodents, non-human primates). Researchers use mouse species to perform assays and better understand pathogenesis of CHIKV. Behaviors of infected rodents are similar to human beings. Arthritis and myositis similar to human symptoms are found in infected young and adult C57BL/6 mouse footpads. Systemic infection appears in mouses infected with CHIKV, including detectable viremia, skeletal muscle damage and chronic tissue damage. However, murine arthritis is usually limited to ipsilateral join, unlike polyarthritis of people infected with CHIKV. Acute symptoms of non-human primates infected with CHIKV are similar to human beings. Symptoms of infected rhesus monkey and cynomolgus monkey are fever, rash, viremia, swollen wrist and ankle joint. Symptoms of infected animals are the same as human beings.

5 Prevention and Detection of Chikungunya Virus

Two CHIKV vaccines have been approvingly available in the global market, named after Ixchiq and Vimkunya respectively. More CHIKV candidate vaccines are in the preclinical or clinical trial stage, e.g. mRNA vaccine, virus vector vaccine. Researches show monoclonal antibodies(mAbs) have potential in prevention and treatment of CHIKV infection. mAbs take effects via neutralizing virus activity during adhesion, entrance and fusion stage, or inhibiting the binding between the virus and its receptor MXRA8. Neutralizing epitopes of E1 and E2 glycoprotein mainly focuses on area A and area B. mAbs show wide applications, but are still in the preclinical screening stage.

According to diagnosis and treatment of Chikungunya fever(2018 edition) in China, detection methods for Chikungunya virus include nucleic acid testing, virus isolation and serological examination etc. Serological examinations can use ELISA, IFA and immunochromatography to detect serum specific IgG or IgG antibody.

Currently, vaccines for preventing Chikungunya fever are not available in China. CHIKV is transmitted via the cycle human-mosquito-human. After 2-5 days infection, high titer viremia is produced in human body. Mosquitoes may be infected after biting infected people. The virus is transmitted via biting others if mosquitoes carry the virus. Thus, Control of CHIKV transmission is to prevent mosquitoes and their bite.