Learning more about the Chikungunya virus

Posted on August 6, 2014   by Jon Fuhrmann

Chikungunya, an emerging viral infection carried by mosquitoes, has been making headlines across the US over the past few weeks. But what is Chikungunya? How does it spread? Jon Fuhrmann investigates.

The American Centre for Disease Control (CDC) first reported the existence of Chikungunya in the Caribbean as recently as December 2013. Since then, the number of infections in Americans returning from the Caribbean have steadily risen and have been confirmed in 35 states – a remarkable feat for a virus that, until less than a year ago, was undetected in the Western hemisphere. To make matters worse, two infected patients in Florida had not travelled at all: mosquitoes within the United States had transmitted the virus for the first time.

Image: Marcello Consolo on Flickr

Chikungunya is transmitted by the tiger mosquito (Aedes albopictus) and the yellow fever mosquito (Aedes aegypti). Discovered in Tanzania in 1952, the virus’s name means “that which bends up” in the language of the Makonde people of Tanzania and Malawi. This is in reference to the extreme joint and muscle pain caused by the virus, which sees many patients writhing in agony. While Chikungunya infections are rarely fatal, chronic arthritis and long-term pain can persist for years after infection in older patients.

Both mosquito species carrying the Chikungunya virus are found in the USA: A. aegypti is present across the southeast of the country, while the more aggressive, A. albopictus, was accidentally introduced in the USA in the 1980s – has since spread along the entire east coast. Besides Chikungunya, these mosquitoes can also spread dengue fever and yellow fever, so they are very much on the radar of public health officials. A mosquito will become infectious within a few days of biting someone who is infected with Chikungunya. By then, the virus will have moved from the mosquito’s gut to its mandibles and can then be transmitted to anyone the mosquito bites.

Professor Tom Solomon, Director of the new Health Protection Research Unit for emerging and zoonotic infections at the University of Liverpool, notes that the risk to the US population arises from tourists returning from the Caribbean infected with the Chikungunya virus. If an infected person gets bitten by a mosquito that can carry the disease, that mosquito can then transmit the virus within the USA. So far, this has only happened in Florida, but as the number of infected patients continues to rise, so does the likelihood of transmission of the disease through domestic mosquitoes. As of 29 July, nearly 400 Chikungunya infections have been reported across the United States, and each of these patients is at risk of being bitten by a mosquito that could then transmit the disease.

That said, the American outbreak is not the first Chikungunya epidemic outside of the virus’s native Africa – several outbreaks have occurred in Asia, and some smaller ones in Italy. Professor Solomon notes that while the disease was initially transmitted only by A. aegypti, a small change in Chikungunya’s DNA was enough to allow it to be transmitted by A. albopictus, which is native to Southeast Asia.

No vaccines or treatments yet exist for the mysterious Chikungunya virus. However, Dr Chioma Okeoma and her colleagues at the University of Iowa are working to understand how the virus replicates in the human body once transmitted by mosquitoes – and how we can stop it. In a recent paper published in the Journal of General Virology, the group studied the role of a protein known as BST-2 in the replication process of the Chikungunya virus once it is inside the body.

BST-2 is a protein that is manufactured en masse when a cell detects the presence of interferons. Interferons are generally produced by cells that are infected by a pathogen to alert the body’s immune system, and to ‘warn’ surrounding cells. Okeoma and her team found that BST-2 protects the body by ‘tethering’ Chikungunya, holding the virus particles close and preventing them from swarming out and infecting other cells.

The researchers compared how the presence or absence of BST-2 in mice affected the spread of the virus in the first 24 hours after infection. Normally, a cell infected with a virus will respond by producing interferons in order to trigger a response from the body’s immune system. However, the researchers found that if BST-2 was not present in a cell infected with Chikungunya virus then interferons were not produced. The implication is that BST-2 is a crucial ingredient in eliciting an immune response to Chikungunya.

BST-2 thus helps the body fight Chikungunya infections in not one but two ways. It tethers the Chikungunya virus particles to stop them from spreading and is also instrumental in informing the immune system of the infection. This explains why the mice without BST-2 had a much higher viral load and, at the same time, a weaker immune response to the virus than those with BST-2.

Before we laud BST-2 as a ‘superhero protein’ it is worth noting that it may also have a number of negative effects. While it protects us by tethering Chikungunya and some other viruses (including retroviruses such as HIV), BST-2 is also thought to facilitate infection with certain flu-like viruses. Furthermore, much higher concentrations of BST-2 proteins are found in cancerous cells compared to healthy ones, suggesting a potential link with cancer that Okeoma and her team are currently investigating. It appears that the relationship between this multifaceted and very complex protein and our health is ambiguous to say the least!

The combination of the beneficial and harmful properties of BST-2 makes it difficult to envision it as suitable for the production of medication. Despite its powerful antiviral properties in relation to Chikungunya and HIV, the possible connection with cancer means that human trials are out of the question in the immediate future. Nevertheless, Okeoma remains hopeful that studying BST-2 in mice will allow her lab to harness the beneficial power of the protein while neutralising its harmful effects.

Mahauad-Fernandez, W., Jones, P., & Okeoma, C. (2014). Critical role for BST-2 in acute Chikungunya virus infection Journal of General Virology DOI: 10.1099/vir.0.068643-0