Fig. 1: Chikungunya viruses (top, yellow) may hitch a ride with monocytes (top left), which mature to macrophages (top right), to joints where they can cause ongoing joint pain long after the virus has been cleared from the blood.
© 2010 L.F.P. Ng
Endemic in many parts of southern and southeastern Asia, including Singapore, Chikungunya fever is a debilitating, mosquito-borne illness that causes rash, joint pain and high fever. The Chikungunya virus causes this disease, but it has been unclear which cells within the body become infected by the virus.
Thanks to an international research team led by Lisa Fong Poh Ng from A*STAR’s Singapore Immunology Network, we now know that the Chikungunya virus infects blood cells called monocytes during the early phase of infection, and that these cells may not only harbor and transport the virus to joints, but could also control viral levels in the blood.
Ng and her co-workers examined blood cells from patients infected with the Chikungunya virus. They detected the virus in monocytes, which are generally involved in fighting viral infections. However, they also observed that higher levels of the virus in these cells were linked to higher levels of the virus in the blood, and in cell culture, the researchers could infect monocytes collected from healthy patients. These findings suggest that monocytes may be involved in the induction of Chikungunya fever by serving as ‘factories’ that churn out new viral particles, sustaining the initial infection by the Chikungunya virus.
As the joint pain caused by an infection with the Chikungunya virus requires the spread of the virus to the joints (Fig. 1), the researchers suggest that infected monocytes may serve to spread the virus they harbor to these locations in the body. This could lead to chronic joint problems that may persist even after initial clearance of the Chikungunya virus infection from the blood.
The human immune system can reduce viral levels in the blood within a few days of infection with the Chikungunya virus. Consistent with this timing, the researchers found that Chikungunya viral levels can be controlled quickly in monocytes in cell culture. The team therefore argues that these cells may also have a role in halting viral spread in the body, probably by secreting antiviral cytokines such as interferon-α, which the team found in the tissue culture media of monocytes that had been exposed to the Chikungunya virus. This dual role of monocytes—to replicate and then to blunt Chikungunya virus infection—could be harnessed to fight the infection in humans.
“Our results provide a better understanding on the basic mechanisms of Chikungunya virus infection and early anti-viral immune responses,” explains Ng, “and will help in the development of future effective control strategies.”
The A*STAR-affiliated researchers mentioned in this highlight are from the Singapore Immunology Network.
