The viruses that cause most childhood diarrheal diseases are covered by several layers of proteins that protect them and allow them to infect their victims. Spanish researchers have managed to measure the mechanical properties of these protein covers, which could lead to new treatments.
Researchers from the Autonomous University of Madrid (UAM), the Carlos III Health Institute (ISCIII) and the National Center for Biotechnology (CNB) have been able to measure the mechanical properties of the multiple protein layers that protect rotavirus.
The results, published in eLife, could open new lines of research for the development of treatments against rotavirus infection, responsible for a large part of diarrheal diseases in childhood from birth to five years.
This study is the first to detail the interaction between the function and mechanical properties of a multilayer virus. The viral particles enclose their genetic material in a protein shell designed to protect, transport and release the viral genome in the host cell.
To achieve this, the structure of the viral particles must be strong enough to protect the viral genome in environments outside the cell and resist attacks from the host’s immune system, guaranteeing a successful infection.
Many double-stranded RNA viruses surround their genome with a characteristic protein layer that incorporates its own molecular machinery to allow the genome to replicate and propagate.
Some of these viruses add additional layers of protein that participate in specific functions. For example, rotavirus has concentrated all the necessary machinery for the interaction and entry into the target cell in the outermost layer of its viral particle.
The complete rotavirus particle consists of three independent protein layers. “This particle and subviral particles that contain one or two layers of protein play different roles during infection,” explains the lead author, Manuel Jiménez-Zaragoza, of the UAM.
“We wanted to see how the interactions between the layers that define these different particles contribute to the replication cycle of the virus,” he adds.
Three layers of proteins
The authors isolated each of the different rotavirus viral particles and subparticles, and studied them using atomic force microscopy (AFM).
The results show the presence of a strong interaction between the thin outer layer and the thick middle layer of the viral particle, which is critical for the protection of the infective virion.
Weaker interactions between the components of the middle layer and between these with the inner layer allow this thick layer to perform its role as an adapter between the internal and external layers, giving it the necessary flexibility to allow the virus to replicate its genome in the host cells, a process known as transcription.
“Our findings reveal how the biophysical properties of the three protein layers are adjusted to allow rotavirus to efficiently infect host cells,” says Pedro de Pablo, another of the authors of the UAM. “This work provides valuable information and important targets for the development of new antiviral strategies,” he concludes.