Against the clock—uncovering the first 30 minutes of viral infection

March 29, 2018 by Rachel Kahn, Imperial College London
Credit: Imperial College London

Researchers are unraveling the crucial first 30 minutes of viral invasion into a human cell.

For a virus attacking a cell, timing is everything. In order to take hold, these invaders must act efficiently, avoiding immune detection and remaining intact whilst they journey through cellular machinery.

However, the intricacies of the early stages of viral life have for years troubled scientists who have been studying these small but detailed particles. Understanding the mechanisms will hopefully help them create new therapeutics for viral diseases.

Work from one team at Imperial is now shining more light on the earliest stages of viral infection, helping to answer some of the questions about what happens once these microbial invaders enter the .

Peter O'Hare, Professor of Virology from the Department of Medicine, leads a group looking into what happens when our cells come under attack from a common family of viruses implicated in everything from cold sores to cancer – the Herpesviruses.

By studying one member of this class of virus (HSV), they are beginning to unravel questions about how viruses get into the host cell and travel to the nucleus, where they hijack the cell's machinery to produce copies of themselves, and how they regulate elements of the host cell required for infection. We asked him more about his latest research.

Why are the first 30 minutes of infection so important?

Knowing what a virus does in the first 30 minutes, and exactly how the viral genome – the virus's genetic material – gets into the cell is critical. We can then study which cellular proteins are used by the virus, and the processes by which it manages to evade any immune response.

If we know about these processes, we can rationally design compounds that interfere with them, and these could make good potential therapeutics for .

A single infected cell; 30 minutes after infection. Blue is the nucleus of the cell. Red are the virus particles themselves. The genome is in green. Credit: Imperial College London
What does the virus do when it finds and enters a host cell?

Like many other viruses, HSV has to find its way to the nuclear pore – a sort of gateway that allows entry into the nucleus of the cell it's infecting. It has a certain time frame to do this before 'alarm bells' start ringing and a host cellular response is triggered to stop its entry.

Because of this, viruses have evolved specific ways to fast-track themselves through the host cell, and we identified a small section of a protein that, if absent, would mean HSV would lose its ability to target itself and enter through the nuclear pore.

HSV does this very efficiently, and we also found that the viral genome is held together very tightly and remains intact in the host cell's cytoplasm. This is interesting as it means the host cell cannot detect viral DNA 'hiding' in the cytoplasm and therefore won't be able to trigger an .

This might not be the same in all cell types but it's certainly an interesting starting point.

In the past, available techniques have made it difficult to trace and measure viral genomes. How did your team manage to do this?

Over the last few years, chemists have been able to take small chemical groups and tag them onto biological molecules, which are precursors for other molecules, like DNA and proteins.

We are using one of these DNA precursors to feed into cells. We can then infect those cells with HSV in the hope that when the virus replicates its DNA, it will take the DNA precursor that we chemically tagged with it. From there, we can purify out the and use it to infect other .

The great thing is, we can chemically tag the DNA precursors with a fluorescent molecule, which means when it is attached to the it will fluoresce, allowing us to detect it and visualise how it infects a cell. So we have now, for the first time, visualised the first 30 minutes of infection and observed the genome traversing across the gateway. There is great excitement over this technology and what it could promise for the future.

What could this new information mean for the future?

We're interested in the long term and this involves understanding the mechanism of an event so we can interfere with it. Having this knowledge puts us in a position to be able to better design therapeutic interventions and we certainly hope our research can feed into this.

Explore further: Zika virus infection alters human and viral RNA

Related Stories

Zika virus infection alters human and viral RNA

October 20, 2016
Researchers at University of California San Diego School of Medicine have discovered that Zika virus infection leads to modifications of both viral and human genetic material. These modifications—chemical tags known as ...

Ebola virus exploits host enzyme for efficient entry to target cells

February 7, 2018
Researchers have identified a key process that enables the deadly Ebola virus to infect host cells, providing a novel target for developing antiviral drugs. The Ebola virus incorporates a cellular enzyme into its virus particles, ...

Human genomic pathways to bronchitis virus therapy

November 18, 2015
Viral replication and spread throughout a host organism employs many proteins, but the process is not very well understood. Scientists at A*STAR have led a collaborative study to learn which host factors play a key role in ...

Scientists established a comprehensive protein interactions map of the replication machinery of a chronic virus

December 20, 2017
Chronic viral infections like HIV or hepatitis are among the biggest threats to human health worldwide. While an acute viral infection usually results in full recovery and effective immune memory, chronic viruses evade the ...

Protein critical to early stages of cellular HIV infection identified

August 8, 2017
When a virus enters a cell, one of the first steps in the process of infecting that cell is removal of the protein coat that surrounds the virus's genetic material. The virus can then produce DNA from its own genes and insert ...

Recommended for you

Drug targets for Ebola, Dengue, and Zika viruses found in lab study

December 13, 2018
No drugs are currently available to treat Ebola, Dengue, or Zika viruses, which infect millions of people every year and result in severe illness, birth defects, and even death. New research from the Gladstone Institutes ...

Faster test for Ebola shows promising results in field trials

December 13, 2018
A team of researchers with members from the U.S., Senegal and Guinea, in cooperation with Becton, Dickinson and Company (BD), has developed a faster test for the Ebola virus than those currently in use. In their paper published ...

Urbanisation and air travel leading to growing risk of pandemic

December 13, 2018
Increased arrivals by air and urbanisation are the two main factors leading to a growing vulnerability to pandemics in our cities, a University of Sydney research team has found.

Researchers discover new interactions between Ebola virus and human proteins

December 13, 2018
Several new connections have been discovered between the proteins of the Ebola virus and human host cells, a finding that provides insight on ways to prevent the deadly Ebola virus from reproducing and could lead to novel ...

Faecal transplants, 'robotic guts' and the fight against deadly gut bugs

December 13, 2018
A simple compound found in our gut could help to stop dangerous bacteria behind severe, and sometimes fatal, hospital infections.

Taking the virus out of a mosquito's bite

December 12, 2018
They approach with the telltale sign—a high-pitched whine. It's a warning that you are a mosquito's next meal. But that mosquito might carry a virus, and now the virus is in you. Now, with the help of state-of-the-art technology, ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.