Human rhinovirus RNA release mechanism revealed

The initiation of viral infection is a unimolecular process, in which only one or a few cells are infected by a single virus. The outcome of an infection from a single virus may depend critically on the stochastic or random nature of the individual physicochemical events involved in the viral cycle. Therefore, it is pertinent to study at the level of individual molecules ( single-molecule ) the physicochemical mechanisms that a virus uses to complete its infective cycle.

Using advanced techniques at the level of individual molecules, a team from the Autonomous University of Madrid (UAM)—made up of researchers in Molecular Biology and Condensed Matter Physics—has delved into the study of the human rhinovirus (RV), the main cause of common cold.

The results, published in the journal Small (Wiley) , have allowed scientists to better understand the release of the virus's genetic content, one of the physicochemical events necessary for the virus to complete its infective cycle.

Detection and quantification of RNA in individual viruses

First, the researchers verified the integrity of the viral particles by acquiring high-resolution topographic images (on the order of nanometers) obtained by atomic force microscopy.

They then implemented several controls to ensure that they were indeed analyzing RNA release in individual viruses. Finally, with the help of force spectroscopy and fluorescence microscopy, they were able to detect the release of RNA and quantify its externalization rate and the energy associated with said process.

“The findings of the study suggest that the release of viral RNA is a stochastic process, regulated by a moderate energy barrier, resulting in a heterogeneous population of viral particles into which different lengths of the RNA molecule had been extruded. This model could be extendable to other viruses of the same genus that share infection mechanisms,” the authors detail.

Additionally, the team discovered that there is a direct relationship between the rate of RNA release and the infectivity of the virus, which has potential implications for the development of antiviral treatments.

“The effects of antiviral compounds or a deleterious mutation of the capsid on the release of RNA revealed a direct correlation between the reaction speed and the infectivity of the virus. The outcome of infection of a host organism by a virus may depend largely on the free energy barrier of this reaction for one or a few virions that can enter the host,” the authors conclude.

human rhinovirus

Human Rhinovirus is a respiratory virus that causes most colds, making it responsible for numerous days of absence from work and school, generating a significant economic impact.

In addition, this virus plays a role in clinical complications such as asthma exacerbation and chronic pulmonary obstruction, a disease that, according to the World Health Organization, is the third cause of death in the world. These complications are especially prevalent in elderly individuals, children, and people with compromised immune systems.

The work has been directed by doctors Mauricio G. Mateu (professor of the Department of Molecular Biology), Alejandro Valbuena (assistant professor of the Department of Molecular Biology) and carried out in collaboration with the group of doctor PJ de Pablo (tenured professor of the department of Condensed Matter Physics).

Bibliographic reference: Valbuena, A., Strobl K., Gil-Redondo, JC, Valiente, L., de Pablo, PJ, Mateu MG Single-Molecule Analysis of Genome Uncoating from Individual Human Rhinovirus Particles, and Modulation by Antiviral Drugs 2023 Wiley Online Library

Doi: 10.1002/smll.202304722

Image: Photography by the Virus and Nanotechnology Engineering group, CBM-UAM. From left From left to right: Luis Valiente, Mauricio G. Mateu, Juan Carlos Gil, Alejandro Valbuena and Judith Escrig./ CBM-UAM