• MXRA8 identified as pivotal receptor in CHIKV entry. • Key mutations drive vector adaptation and global spread. • CHIKV exploits autophagy to enhance viral replication. • Neutralizing antibodies inform vaccine and therapy design. • Integrated control strategies crucial for outbreak prevention. Chikungunya virus (CHIKV) is an arthropod-borne alphavirus that causes an abrupt febrile illness typically marked by intense arthralgia, rash, and profound fatigue. Following transmission predominantly through Aedes mosquitoes, the virus is able to infect a broad range of host cell types, such as fibroblasts and macrophages, resulting in acute viremia with high viral titers and, in a subset of patients, prolonged arthritis-like manifestations. CHIKV carries a positive-sense, single-stranded RNA genome that encodes nonstructural proteins essential for viral replication as well as structural components required for virion assembly and host-cell entry. The MXRA8 receptor has recently been identified as a central determinant of viral entry and cellular tropism. Genomic analyses place CHIKV into three major lineages, and certain amino-acid substitutions, most notably the E1-A226V change, have been linked to improved adaptation to Aedes vectors and more efficient transmission. The host immune reaction is multifaceted, involving type I interferons, neutralizing antibodies, and virus-specific T-cell activity. Even so, the virus is able to bypass several of these defenses through established evasion mechanisms, which may contribute to prolonged infection in some cases. Given the continued expansion of Aedes mosquito populations driven by climate change, integrated vector-management strategies remain essential. These include chemical, biological, and genetic approaches aimed at curbing mosquito densities and reducing the impact of insecticide resistance. Sustained global surveillance and coordinated public-health interventions are critical to mitigating the growing burden of CHIKV and addressing the recent surge in large-scale outbreaks.
Hamrahjoo et al. (Sun,) studied this question.