New imaging technology set to reveal secret life of virus in cells

New imaging technology set to reveal secret life of virus in cells

One of the challenges of unlocking the secret lives of tiny biological agents - like viruses inside living cells - is how to get close up without disturbing their structure and behavior.

Now, using high-end imaging, a team from the US has found a way to label and study the respiratory syncytial virus (RSV) and its activity in living cells that could become a general method for unlocking the secrets of many important RNA viruses.

With the new approach, Philip Santangelo - associate professor at Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University - and colleagues say scientists could study how the RSV virion or infective virus particle enters cells, how it replicates, how many genomes it inserts into its hosts, and perhaps discover why some types of lung cells manage to avoid infection.

In a recent issue of the journal ACS Nano, they write about how they used the new imaging technique - which brings together multiply-labeled tetravalent RNA imaging probes (MTRIPS) and direct stochastic optical reconstruction microscopy (dSTORM) - to probe the life of RSV in living cells.

Prof. Santangelo says:

We want to develop tools that would allow us to get at how the virus really works. We really need to be able to follow the infection in a single living cell without affecting how the virus infects its hosts, and this technology should allow us to do that."

Scientists using such an approach could provide important information for developing new antiviral drugs and vaccines against severe RSV infections.

Infection with RSV can be severe

RSV causes infections of the lungs and respiratory tract. The virus is so common that by the age of 2, most children have had it.

In adults and older, healthy children, RSV causes mild symptoms, rather like a common cold, and self-care is usually enough to relieve them.

But RSV infection can be severe in premature babies and infants who are already sick, as well as adults with weakened immune systems or older people with heart and lung diseases. In these cases, it can develop into pneumonia and bronchitis, requiring hospitalization and leading to long-term consequences.

RSV is a slippery character to study

RSV poses some big challenges to scientists. For one thing, it takes on many forms, ranging from 10-micron filaments to ordinary spheres. It can insert more than one genome into the host cell, and its structure and orientation is disordered, making it difficult to characterize.

The probe technology the team used, MTRIPS, quickly attaches to RNA within cells. The probe uses several fluorescent chemicals to show the presence of the viral RNA. This allowed the team to see where it goes in host cells, and to observe infectious particles leaving the cells to spread infection.

Prof. Santangelo adds:

Being able to see the genome and the progeny RNA that comes from the genome with the probes we use really give us much more insight into the replication cycle.

This gives us much more information about what the virus is really doing. If we can visualize the entry, assembly and replication of the virus, that would allow us to decide what to go after to fight the virus."

Unlocking secrets of other RNA viruses

Although RSV will be their first target, the team believes their imaging technique could be used to probe the lives of other RNA viruses, such as influenza and Ebola.

They also hope the technique will help solve another mystery: why certain lung cells become severely infected with RSV, while others appear to escape relatively unscathed.

Prof. Santangelo says if you look at a field of cells, you can see big differences from cell to cell. They couldn't understand this at all:

"If we can figure out why some cells are exploding with virus while others are not, perhaps we can figure out a way to help the bad ones look more like the good ones."

Funds from the National Institute of General Medical Sciences of the National Institutes of Health helped finance the study.

In a study published recently in the Proceedings of the National Academy of Sciences, another team of US researchers found that dogs in the home may protect against infection, including RSV.

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Section Issues On Medicine: Disease