Virology

Chikungunya virus is a member of the genus Alphavirus, and family Togaviridae. Chikungunya virus features an icosahedral capsid surrounded by a lipid envelope, with a diameter ranging from 60 to 70 nm. It was first isolated in 1953 in Tanzania and is an RNA virus with a positive-sense single-stranded genome of about 11.6kb. It is a member of the Semliki Forest virus complex and is closely related to Ross River virus, O'nyong'nyong virus, and Semliki Forest virus. Because it is transmitted by arthropods, namely mosquitoes, it can also be referred to as an arbovirus (arthropod-borne virus). In the United States, it is classified as a category B priority pathogen, and work requires biosafety level III precautions.

Three genotypes of this virus have been described, each with a distinct genotype and antigenic character: West African, East/Central/South African, and Asian genotypes. The Asian lineage originated in 1952 and has subsequently split into two lineages – India (Indian Ocean Lineage) and South East Asian clades. This virus was first reported in the Americas in 2014. Phylogenetic investigations have shown two strains in Brazil – the Asian and East/Central/South African types – and that the Asian strain arrived in the Caribbean (most likely from Oceania) in about March 2013. The rate of molecular evolution was estimated to have a mean rate of 5 × 10−4 substitutions per site per year (95% higher probability density 2.9–7.9 × 10−4).

The chikungunya virus genome consists of structural and non-structural proteins as typical of alphavirus genomic organization.The structural proteins, including the capsid, E3, E2, 6K and E1, are responsible for encapsulating the viral genome and assembling new viral particles. These proteins are critical for viral entry into host cells. Meanwhile, the non-structural proteins, nsP1, nsP2, nsP3, and nsP4, play essential roles in viral replication, translation, and immune evasion.

Viral replication

The virus consists of four nonstructural proteins and three structural proteins. The structural proteins are the capsid and two envelope glycoproteins: E1 and E2, which form heterodimeric spikes on the viron surface. E2 binds to cellular receptors in order to enter the host cell through receptor-mediated endocytosis. E1 contains a fusion peptide which, when exposed to the acidity of the endosome in eukaryotic cells, dissociates from E2 and initiates membrane fusion that allows the release of nucleocapsids into the host cytoplasm, promoting infection.The mature virion contains 240 heterodimeric spikes of E2/E1, which after release, bud on the surface of the infected cell, where they are released by exocytosis to infect other cells.

Macrophages, as phagocytic innate immune cells, serve as the first line of defense against viral infections, playing a key role in inflammation and adaptive immune activation; however, in Chikungunya virus infection, they can act as cellular reservoirs, contributing to persistent viral presence and chronic inflammation.Recent studies suggest that Chikungunya virus glycoproteins (E1 and E2) not only facilitate viral entry, assembly, and exit but also interfere with intracellular barriers to enhance virion production and spread in human macrophages (in vitro).

Research

Chikungunya is one of more than a dozen agents researched as a potential biological weapon.

This disease is part of the group of neglected tropical diseases.

Chikungunya-related products

Recombinant Protein

Monoclonal Antibody