Proteins on viral surface linked to formation of Alzheimer’s plaque

Viruses are both dead and alive. They can reproduce inside living cells and exploit the cellular machinery of their host to their benefit. However, before entering a host cell, viruses can be considered nanoparticles. In an international collaboration, researchers at Stockholm University and Karolinska Institutet have found that viruses and nanoparticles share another important property; they both become covered by a layer of proteins when they encounter the biological fluids of their host before they find their target cell. This layer of proteins on the surface influence their biological activity significantly.

Examines protein corona on RS virus

“Imagine a tennis ball falling into a bowl of milk and cereals,” says Kariem Ezzat, researcher at Stockholm University and lead author of the study. “The ball is immediately covered by the sticky particles in the mix and they remain on the ball when you take it out of the bowl. The same thing happens when a virus gets in contact with blood or lung fluids that contain thousands of proteins. Many of these proteins immediately stick to the viral surface forming a so-called protein corona.”

The researchers studied the layer of proteins on the surface, the protein corona, of respiratory syncytial virus (RSV) that had encountered different biological fluids. RSV is the most common cause of acute lower respiratory tract infections in young children worldwide, leading up to 34 million cases and 196,000 fatalities each year.

“The protein corona signature of RSV in the blood is very different from that in lung fluids,” says Kariem Ezzat. “It is also different between humans and other species such as rhesus macaque monkeys, which also can be infected with RSV”.

“The virus remains unchanged on the genetic level,” he continues. “It just acquires different identities by accumulating different protein coronae on its surface depending on its environment. This makes it possible for the virus to use extracellular host factors for its benefit, and we’ve shown that many of these different coronae make RSV more infectious.” 

Connect viruses and amyloid plaques

The researchers have also found that viruses such as RSV and herpes simplex virus type 1 (HSV-1) can bind so-called amyloid proteins. These proteins aggregate into plaques that play a part in Alzheimer’s disease where they lead to neuronal cell death.

The mechanism behind the connection between viruses and amyloid plaques has been hard to find, but the new study suggests that HSV-1 is able to accelerate the transformation of soluble amyloid proteins into thread-like structures that constitute the amyloid plaques. In animal models of Alzheimer’s disease, the researchers saw that mice developed the disease within 48 hours of infection in the brain. In absence of an HSV-1 infection the process normally takes several months.

Important knowledge for the development of vaccine

“The novel mechanisms described in our paper can have an impact not only on understanding new factors determining how infectious a virus is, but also on devising new ways to design vaccines,” says Kariem Ezzat. “In addition, describing a physical mechanism that links viral and amyloid causes of disease adds weight to the increasing research interest in the role of microbes in neurodegenerative disorders such as Alzheimer’s disease and opens up new avenues for treatments.”

Last authors of the study are Samir El-Andaloussi at the Department of Laboratory Medicine, Karolinska Institutet, and Anna-Lena Spetz, professor at Stockholm University who is also associated to Karolinska Institutet. The project was carried out in collaboration with University of Eastern Finland, University of Oxford and Queen’s University Belfast.

The research was financed by the Swedish Society for Medical Research (SSMF), the Swedish Research Council, Stockholm University, the Swedish Foundation for Strategic Research, the Instrumentarium Science Foundation, the Academy of Finland, the Swedish Heart-Lung Foundation, Karolinska Institutet, and through the Regional Agreement on Medical Training and Clinical Research (ALF) between Stockholm County Council and Karolinska Institutet.

This news article is based on a press release from Stockholm University.