A new word in virology
Antiviral drugs that suppress replication are able to selectively affect the most dangerous viruses, – these are the results of a study performed using a new high-performance system that allows simultaneous monitoring of a large number of single infected cells.
A group of researchers from Pennsylvania State University, Duke University (North Carolina) and the University of Texas, led by Craig Cameron, set out to identify the features of the action of antiviral drugs on a single infected cell. Prior to this, similar studies were conducted on a population of infected cells. But the authors believe that each cell and each virus is individual, and the results of studies on the whole population are averaged and not accurate enough.
Therefore, it became necessary to create a tool that allows taking into account the characteristics of each individual cell, as well as to study the mechanism of the drugs' effect on a specific virus.
The structure of a microfluidic chip that allows to study the behavior of the virus in a single cell. Source: Penn State.
A modified poliovirus was bred that produces a fluorescent green protein. The more intensively the virus divides inside the cell, the more this protein is produced. To simultaneously study such a large number of infected cells, which would be sufficient to obtain reliable data, a microfluidic chip was created, which made it possible to observe up to 6,400 cells simultaneously.
The study of a single cell infected with a virus. The modified virus produces a green protein, and as the amount of virus inside the cell increases, the amount of this protein increases. Thus, it is easy to track the replication of the virus inside the cell. Source: Penn State.
The poliovirus-infected cells were treated with 2’-C–methyladenosine, a viral polymerase inhibitor that inhibits the reproduction of the virus. This substance is the basis of the drug sofosbuvir. It is used in combination with other drugs for the treatment of hepatitis C. As has been proven in previous studies, sofosbuvir destroyed about 50% of viruses. But the researchers were surprised by the fact that it had a selective effect on the most dangerous viruses – those that multiplied inside the infected cell most quickly.
The researchers also tracked the behavior of the virus inside the cell: the time of the start of replication, the rate of replication, the maximum level of growth of the virus. Using an individual approach, they were able to show which of the life stages of the virus can be influenced to effectively combat it.
With the help of a new microfluidic chip, it will be possible to identify specific factors that vary in different cells and viruses and affect the outcome of treatment, as well as develop new more effective antiviral drugs.
Article by Feng Guo et al. Single-Cell Virology: On-Chip Investigation of Viral Infection Dynamics is published in the journal Cell Reports.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on Penn State Science: Survival of the least-fit: antiviral drug selectively targets the nastiest viruses.