Etiology

Chikungunya virus is an arthropod-borne virus (arbovirus) that belongs to the family Togaviridae and to the genus Alphavirus. The virus is related to the Semliki Forest antigenic complex, a group of viruses that may be associated with joint symptoms in humans.[22] Several species of Aedes mosquitoes can transmit the virus; however, Aedesaegypti and Aedesalbopictus are the most common vectors. These mosquitoes can be identified by their striped appearance and their standing position with a straight body. Only the bite of the female mosquito is considered to be infective as the blood meal is required for formation of eggs.

The virus is maintained in nature by 2 cycles: sylvatic and urban. In the sylvatic cycle, Aedes mosquitoes transmit the disease to primates, rodents, and birds. Humans get infected when traveling in forested areas. In the urban cycle, the mosquitoes transmit the disease among humans.[23]

Chikungunya virus is an RNA virus that includes 3 phylogenetically separated lineages. There are Asian and West African lineages, but the South/East/Central lineage is responsible for the largest number of cases starting from the epidemics in Réunion Island.[22]

A aegypti, the mosquito responsible for the transmission of yellow fever and dengue, was the main vector of the virus before 2005. Since then, A albopictus (also known as the Asian tiger mosquito) has become the most common vector. This is likely because of a single mutation in the envelope protein gene E1-A226V, which allowed the virus to adapt to A albopictus, a mosquito that thrives in temperate regions with a wider global distribution, including in urban areas in Europe and the US.[24]

In the US, A aegypti is distributed in the southeast and in a few spots in the states bordering Mexico. This mosquito is commonly found indoors with larvae breeding in containers inside households. A albopictus also has a predominant distribution in the southeast US, but the range is more ample, extending to Illinois, New York, and Pennsylvania. This mosquito is found predominantly outdoors. Both A aegypti and A albopictus are aggressive biters that attack during the daytime with a peak at dusk.[25]

Coinfection with dengue and Zika viruses is possible.

Pathophysiology

Chikungunya virus is transmitted most commonly by mosquito bites and less commonly by maternal-fetal transfer. Transmission via blood transfusion is only theoretical, although one case of possible blood-borne transmission has been documented in a nurse caring for a patient with an imported infection.[26][27] ​After an incubation period of about 2 to 4 days (total range 1-12 days), the symptoms of the acute phase ensue. The clinical manifestations correlate with high viral load that can reach up to 10⁸ viral particles/mL of blood, and high concentration of type I interferons and other pro-inflammatory cytokines and chemokines.

The virus infects fibroblasts and other cells via endocytosis. The single-stranded RNA is released in the cytoplasm of infected cells and is transformed into double-stranded RNA (dsRNA) using a replicase and viral RNA polymerase. This dsRNA has the ability to interact with several toll-like receptors (3,7, and 8) and the retinoic acid-inducible gene I (RIG-I)-like receptor. The resultant inflammasome causes the release of type I interferons.

The initial innate inflammatory response is followed 1 week later by adaptive immunity with T-cell and antibody-mediated responses.[28] This response coincides with the infiltration of immune cells into infected joints and surrounding tissues.[10]

The majority of cases resolve after the initial phase; however, a significant subset of patients may develop chronic disease with arthritis and arthralgias.[29]​ It has been speculated that this may be a consequence of massive initial infection of monocytes/macrophages that eventually migrate to synovial tissues and cause chronic viral infection and continuous triggering of the inflammatory response.[30]

Classification

Universal protein resource (Uniprot) classification

The taxonomic tree of chikungunya virus is:

  • Virus: ssRNA viruses: SSRNA positive-strand viruses, no DNA stage: Togaviridae: Alphavirus: SVF Complex: CHIKV.[1][2]

Phylogenetic classification

There are 3 phylogenetically distinct strains of CHIKV:

  • The East-Central-South-African (ECSA) genotype, of which a subtype, the Indian Ocean lineage (IOL), is responsible for the largest outbreak

  • The Asian genotype

  • The West African genotype.[3]

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