Chikungunya is a viral infection transmitted to humans through the bites of infected Aedes mosquitoes, primarily Aedes albopictus and Aedes aegypti. The virus can also infect animals, including monkeys, birds, cattle, and rodents. Symptoms typically appear 2-4 days after infection and include a sudden onset of fever, often accompanied by joint pain. The fever usually lasts for 2-7 days, while joint pain can persist for weeks, months, or even years. The mortality rate is less than 1 in 1,000. Outbreaks of chikungunya have been reported in Asia, Europe, and the Americas since 2004.
The chikungunya virus (CHIKV) has a single-stranded, positive-sense RNA genome containing approximately 11,800 nucleotides. This genome encodes two open reading frames. The virus's nucleocapsid, which houses the RNA genome, is enclosed within a protective lipid bilayer called the envelope. Embedded within the envelope are approximately 80 glycoprotein spikes, which are anchored to the viral envelope at their C-termini.
The virus produces a structural polyprotein from a subgenomic mRNA. This polyprotein contains the five structural proteins: capsid (C), E3, E2, 6K, and E1. The capsid protein is cleaved from the polyprotein and encapsidates the viral RNA. The remaining envelope polyprotein precursor (E3-E2-6K-E1) is transported to the endoplasmic reticulum, where host enzymes process it into the individual E3, E2, and E1 proteins. These proteins assemble into hetero-trimeric spikes on the virus's surface. The E1 and E2 proteins within these spikes play crucial roles in recognizing host cell receptors, mediating cell entry via pH-dependent endocytosis, and facilitating viral budding.
Chikungunya virus (CHIKV) is an arthropod-borne virus belonging to the Alphavirus genus within the Togaviridae family. It is primarily transmitted to humans through the bites of infected mosquitoes, particularly Aedes aegypti and Aedes albopictus . The virus causes Chikungunya fever, characterized by sudden onset of fever, severe joint pain, muscle pain, headache, nausea, fatigue, and rash .
The CHIKV virion is enveloped and contains a single-stranded positive-sense RNA genome of approximately 11.8 kilobases. The viral envelope is derived from the host cell’s plasma membrane and includes two major glycoproteins, E1 and E2, along with a small 6K peptide . The E1 glycoprotein plays a crucial role in the virus’s ability to fuse with host cell membranes, facilitating viral entry and infection .
During the 2005-2006 Chikungunya outbreaks, a significant mutation was identified in the E1 glycoprotein at amino acid position 226, where alanine was replaced by valine (A226V) . This mutation enhanced the virus’s ability to infect and replicate in Aedes albopictus mosquitoes, which are more widespread than Aedes aegypti . Consequently, the A226V mutation increased the epidemic potential of CHIKV by enabling more efficient transmission to human populations .
Recombinant CHIKV E1 glycoprotein, including the A226V mutant, is produced in insect cells for research purposes . The recombinant protein is a polypeptide chain containing amino acids 1-415, with the alanine at position 226 mutated to valine . This recombinant protein is used in various applications, including enzyme-linked immunosorbent assays (ELISA) and Western blotting, to study the virus’s properties and develop diagnostic tools .
The A226V mutation has significant implications for CHIKV transmission and epidemiology. By increasing the virus’s ability to infect Aedes albopictus, the mutation has facilitated the spread of CHIKV to new geographic regions where this mosquito species is prevalent . This has led to larger and more widespread outbreaks, posing a greater public health challenge .