UniProt release 7.3

Chikungunya virus annotation

The Chikungunya virus has made a severe outbreak in French island of Reunion and also in Mauritius, Seychelles, Mayotte and Madagascar, all located off the southeast coast of Africa. The virus is not deadly, but causes severe fever, rash, arthritis and joint pain. These symptoms are at the origin of the name Chikungunya, which means in Swahili "that which bends up".

The virus belongs to the large family of Togaviridae, genus Alphavirus. This family includes exotic viruses like O'nyong nyong and Igba Oro, which are very closely related to Chikungunya and induce actually the same disease in humans. Interestingly, the name O'nyong nyong comes from the Nilotic language of Uganda and Sudan and means "weakening of the joints".

Chikungunya is transmitted by mosquitos, in which it infects salivary glands, but the natural host reservoir is constituted of different types of monkeys.

The molecular strategy used by Alphaviruses to replicate and hijack cellular defense is very surprising:

After virus entry into the target cell, the mRNA(+) genome is translated into a nonstructural polyprotein, which starts discretely to replicate the genome in the cytoplasm. After this early phase where the virus avoids cellular defense by restraining its activity, the nonstructural polyprotein is processed into four proteins. There goes the virus at full strength to replicate large amount of his genome, and innocently transcribes also a subgenomic 26S RNA. This replication has a drawback: it creates dsRNA by genome and antigenome hybridization.

No eukaryotic cell can accept such an offence: dsRNA is a signature of viral infection. The host cell reacts violently: human PKR is strongly activated by the dsRNA, resulting in a complete shutoff of cellular translation through inactivation of early initiation of translation factor EIF2A.

But this powerful cellular defense was expected by the virus. The 26S mRNA possesses a unique feature in biology: an enhancer element which allows the mRNA to be translated independently of EIF2A. This 26S RNA codes for the structural proteins, which are now the only proteins synthesized by the cell! These structural proteins form new virions which bud from the doomed cell to find new targets.

The following are examples of new Alphavirus entriesin release 7.3:

• Chikungunya virus (strain S27-African prototype): Nonstructural polyprotein, Structural polyprotein
• O'nyong-nyong virus (strain Gulu): Nonstructural polyprotein, Structural polyprotein
• Togavirus prototype - Semliki forest virus: Nonstructural polyprotein, Structural polyprotein