Chikungunya virus (CHIKV) is a single positive-standard RNA virus in the alphavirus genus of the family of Togaviridae (1). The genome is about 11.8kb in length, including the 5′ -terminal non-coding region (5′ UTR), two independent open reading frames (ORF), 1 poly A tail and 3′ UTR, encoding four non-structural proteins (nsP1, nsP2, nsP3, nsP4) and six structural proteins (capsid protein C, envelope protein E3, E2,6K, E1, and TF). The genes encoding the viral envelope proteins have been mutated in recent decades, which facilitated CHIKV transmission by Aedes albopictus (2). CHIKV has four genotypes: East-Central-South African genotype (ECSA), West African genotype, Asian genotype and Indian OceanLineage genotype (IOL). Among them, the Asian and Indian Ocean Lineage genotypes were derived from ECSA. The ECSA and Asian genotypes are mainly transmitted by Aedes aegypti, and the Indian Ocean genotype has acquired the ability (3, 4) to transmit through Aedes albopictus after genetic mutations occur. CHIKV can be inactivated by 70% ethanol, l% sodium hypochlorite, 2% glutaraldehyde, and lipid solvents, peracetic acid, and other disinfectants. CHIKV is relatively stable at minus 40 degrees, and it can be inert by heating to above 58 degrees. Although CHIKV infection is usually a self-limiting disease, some patients develop persistent joint pain after the acute phase that may last for months or years (5, 6).

CHIKV belongs to the “New World” group of alphaviruses, which mainly cause musculoskeletal inflammatory diseases such as arthralgia, arthritis, and myalgia, classified as “arthritis virus”, including Chikunonia, Ross River virus (RRV), Ballmach Forest virus (BFV), Group Sindbis and Mayaro (Mayv) (14, 15). CHIKV infects multiple cell types, including dendritic cells, and macrophages. Synovial fibroblasts, endothelial cells, and myocytes. In the human body, osteoblasts can also be infected, causing arthropathy and erosive disease (16) in patients with chronic arthritis.

On the viral surface, the heterodi-and trimers of the structural proteins E1 and E2 proteins form “viral spikes”, and the glycoprotein E2 is responsible for binding to the receptor, while E1 is responsible for the fusion of (17) to the membrane. Given that CHIKV infects multiple types of cells, the cellular proteins that interact with the virus are also diverse in (18). Mammalian cell receptors known for CHIKV include prohibition (PHB), TIM-1, MXRA8, CD147, lectin DC-SIGN, and ATP synthase subunit and FHL1 (19–25). Furthermore, other phosphatidylserine-binding proteins, such as Axl, TIM-4 and TIM-1, have also been shown to promote (26–30) in CHIKV-infected cells. Otherwise, autophagy apoptosis is an important infection mechanism. It has been shown that CHIKV initiates apoptosis through both endophytic and exogenous pathways in HeLa cells, as well as in primary fibroblasts. By hiding within these apoptotic bleeding sites, CHIKV is able to infect adjacent cells. These infectious foci infect macrophages like Trojan viruses, and interestingly, the replication process of this cell-infected virus in macrophages does not produce a proinflammatory response, constituting the mechanism (31), by which CHIKV invades the host cell and escapes the host response. After infection, the incubation period is 3–7 days, in the acute phase, and the most common symptoms are high fever, stiffness, headache, photophobia and ecchymosis rash or punctate rash. Similar to other arboviruses, DENV and ZIKV, the peak of viremia in CHIKV-infected people matched the duration of fever for (32–34), and hospitalized cases had higher viremia than those that did not require hospitalization. Roughly estimated, 30–40% of infected individuals experience some long-term sequelae, including persistent arthralgia and / or arthritis, with about 37% having severe persistent arthralgia. Some studies show that patients older than 40 years, of the female gender, with higher levels of CXCL8, detected in the acute phase of the disease have been shown to associate (35–37) with persistent arthralgia in CHIK. CHIKV susceptibility and in vitro single-cell correlation studies showed that the arthritis-related genes RANTES / CCL5 and IL-8 significantly upregulate (38) in infected human synovial fibroblasts. Following viral replication in vivo, the cells target muscle, joints, and skin fibroblasts, and these tissue cell damage was also observed in human biopsy samples. A study of neonatal and adult mouse models with IFN knockout found that the severity of CHIKV infection was (39) associated with the IFN- / R signaling pathway.

Despite the prevalence of CHIKV in many regions, no marketed vaccine is available. Treatment of CHIKV-infected patients mainly provides symptom relief through the use of anti-inflammatory drugs, such as methotrexate, sulfasalazine, leflunomide, and hydroxychloroquine, which has been utilized but with limited efficacy (40, 41). A wide range of CHIKV vaccine candidates under preclinical development, including whole-virus inactivated vaccine (42, 43), VEE / CHIKV chimeric vaccine, recombinant adenovirus vector vaccine, DNA-and mRNA-based CHIKV vaccine, and the live attenuated vaccine (44–50) with stronger and longer immune response, are currently in clinical research phase I-III, and we need to focus on the antibody dependence (ADE) phenomenon (51), with a breakthrough in future vaccine development.

CHIKV is spreading rapidly in many countries, and the vaccination of susceptible people is the most effective way to control the infection, and we can expect a CHIKV vaccine to be available to the general public in perhaps 5–10 years. Before vaccines and specific drugs are put on sale, we still need to strengthen CHIKV testing for suspected acute neurological symptoms and conduct timely detection of cases and treatment of patients to contain the spread of the epidemic.

YT, LC, and XinH: conceptualization. XibH and XinH: methodology. HL and HT: resources. YT and XinH: writing-original draft preparation. LC: writing-review and editing. LW: visualization. XibH: supervision. SL: project administration. YT: funding acquisition. All authors contributed to the article and approved the submitted version.