Monkey
kidneys and old-school science: Inside Melbourne's coronavirus breakthrough: An
old-school science technique allowed Melbourne’s Doherty Institute to grow
coronavirus in a flask, the first lab outside China to do so.
The important breakthrough allows
scientists to immediately develop much better tests for the virus. And it is a
crucial first step towards developing treatments or a vaccine. Most diagnostic
labs around the world use cutting-edge genetic sequencing techniques to test
for viruses.
The
Doherty Institute for Infection and Immunity, based in Parkville, is one of the
few to maintain extensive cell lines, which allows it not only to test for but
also to grow a wide variety of viruses. "It’s costly, and it needs skills
that are not generally available these days," says Dr Mike Catton, the
institute's deputy director. "We have a mix of the old and the new, the
classical and the cutting edge. I’d say we’re the first among equals – although
my colleagues might not like that."
On Friday a man in his 50s, who was visiting from China and had respiratory symptoms, was brought into the Monash Medical Centre at Clayton. Within hours, a nose swab was under the microscope at the Doherty. The first step was to check the virus' genetic code. By 2.15am on Saturday the team had it – and it was a perfect match for the Wuhan coronavirus.
As the announcement of Australia’s first case of coronavirus reverberated around the nation, the team were already onto the next step: trying to grow the virus in a flask. This was a far more difficult challenge, but crucial. A live virus allows other researchers to develop more effective tests for it.
"It’s a key step in the development of vaccines," says Dr Catton. Labs around the world had tried without success to do it. The Chinese have grown a sample but have not yet shared it with the international community. But the Doherty had been preparing for this for years.
Many viruses are fussy, and will grow only in a certain type of cell. The lab’s freezers house a huge collection of cells from humans and animals. Among them is the institute’s secret weapon: a line of monkey-kidney cells.
"This particular monkey cell line is almost the best cell line there is, because it just grows so many viruses," says Dr Julian Druce, head of the Doherty’s virus identification lab. Dr Catton says: "It’s an art, and Julian is the artist."
Material from the infected man was placed in a flask filled with a layer of monkey cells. The Doherty’s lab is extremely secure, so the easiest way for the scientists to watch their test was via a video camera on top of the flask. Many team members would get up at night to watch the camera feed online.
"That was a bit of fun," says Dr Catton. "If you’re into that sort of thing – I guess maybe we need to get out more." The researchers watched the cells. If they died, it was a sign the coronavirus was active. Vision released by the institute shows the transparent cells turning black – a few at first, and then more and more until the dish is filled with death.
The living virus will now be used to develop an "antibody test", which can tell if someone has coronavirus even if they are not showing symptoms. That will allow authorities to work out the true scale of the outbreak. The Doherty will also sequence its genes so it can be properly compared with other cases in China, allowing it to work out if the virus is mutating.
And when enough copies of the virus have grown in the monkey cells, they will be "harvested" and sent to other labs around Australia and the world– including CSIRO researchers who are hoping to give animals the virus to test potential treatments.
(Peter Doherty Institute: Finding solutions to prevent, treat and cure infectious diseases and understanding the complexities of microbes and the immune system requires innovative approaches and concentrated effort.
This is why The University of Melbourne – a world leader in education, teaching and research excellence – and The Royal Melbourne Hospital – an internationally renowned institution providing outstanding care, research and learning –partnered to create the Peter Doherty Institute for Infection and Immunity (Doherty Institute); a centre of excellence where leading scientists and clinicians collaborate to improve human health globally.
Located in the heart of Melbourne’s Biomedical Precinct, the Doherty Institute is named in honour of Patron, Laureate Professor Peter Doherty, winner of the 1996 Nobel Prize in Physiology or Medicine for discovering how the immune system recognises virus-infected cells.
Under the expert guidance of Director, University of Melbourne Professor Sharon Lewin, a leader in research and clinical management of HIV and infectious diseases, the Doherty Institute has more than 700 staff who work on infection and immunity through a broad spectrum of activities. This includes discovery research; diagnosis, surveillance and investigation of infectious disease outbreaks; and the development of ways to prevent, treat and eliminate infectious diseases.)
What are viruses? What to know about viruses?
Viruses
are microscopic organisms that exist almost everywhere on earth. They can
infect animals, plants, fungi, and even bacteria. Sometimes a virus can cause a
disease so deadly that it is fatal. Other viral infections trigger no
noticeable reaction.
A
virus may also have one effect on one type of organism, but a different effect
on another. This explains how a virus that affects a cat may not affect a dog. Viruses
vary in complexity. They consist of genetic material, RNA or DNA, surrounded by
a coat of protein, lipid (fat), or glycoprotein. Viruses
cannot replicate without a host, so they are classified as parasitic. They are
considered the most abundant biological entity on the planet.
Here
are some key points about viruses. More detail is in the article. Viruses are
living organisms that cannot replicate without a host cell. They are considered
the most abundant biological entity on the planet. Diseases caused by viruses
include rabies, herpes, and Ebola. There is no cure for a virus, but
vaccination can prevent them from spreading.
What are viruses?
Effects
of viruses can range from life-threatening to virtually symptomless. Almost
every ecosystem on Earth contains viruses. Before entering a cell, viruses
exist in a form known as virions. During this phase, they are roughly
one-hundredth the size of a bacterium and consist of two or three distinct parts:
- genetic
material, either DNA or RNA
- a
protein coat, or capsid, which protects the genetic information
- a
lipid envelope is sometimes present around the protein coat when the virus is
outside of the cell
Viruses
do not contain a ribosome, so they cannot make proteins. This makes them
totally dependent on their host. They are the only type of microorganism that
cannot reproduce without a host cell.
After
contacting a host cell, a virus will insert genetic material into the host and
take over that host's functions. After infecting the cell, the virus continues
to reproduce, but it produces more viral protein and genetic material instead
of the usual cellular products. It is this process that earns viruses the
classification of parasite.
Viruses
have different shapes and sizes, and they can be categorized by their shapes. These
may be:
- Helical:
The tobacco mosaic virus has a helix shape.
- Icosahedral,
near-spherical viruses: Most animal viruses are like this.
- Envelope:
Some viruses cover themselves with a modified section of cell membrane,
creating a protective lipid envelope. These include the influenza virus and
HIV.
- Other
shapes are possible, including nonstandard shapes that combine both helical and
icosahedral forms.
Sources
Viruses
do not leave fossil remains, so they are difficult to trace through time.
Molecular techniques are used to compare the DNA and RNA of viruses and find
out more about where they come from. Three competing theories try to explain
the origin of viruses.
Regressive,
or reduction hypothesis: Viruses started as independent organisms that became
parasites. Over time, they shed genes that did not help them parasitize, and
they became entirely dependent on the cells they inhabit.
Progressive,
or escape hypothesis: Viruses evolved from sections of DNA or RNA that
"escaped" from the genes of larger organisms. In this way, they
gained the ability to become independent and move between cells.
Virus-first
hypothesis: Viruses evolved from complex molecules of nucleic acid and proteins
either before or at the same time as the first cells appeared on Earth,
billions of years ago
Transmission
A
virus exists only to reproduce. When it reproduces, its offspring spread to new
cells and new hosts. The makeup of a virus affects its ability to spread. Viruses
may transmit from person to person, and from mother to child during pregnancy
or delivery. They can spread through:
- touch
- exchanges
of saliva, coughing, or sneezing
- sexual
contact
- contaminated
food or water
- insects
that carry them from one person to another
Some
viruses can live on an object for some time, so if a person touches an item
with the virus on their hands, the next person can pick up that virus by
touching the same object. The object is known as a fomite. As the virus
replicates in the body, it starts to affect the host. After a period known as
the incubation period, symptoms may start to show.
What happens if viruses change?
When a
virus spreads, it can pick up some of its host's DNA and take it to another
cell or organism. If the virus enters the host's DNA, it can affect the wider
genome by moving around a chromosome or to a new chromosome.
This
can have long-term effects on a person. In humans, it may explain the
development of hemophilia and muscular dystrophy. This interaction with host
DNA can also cause viruses to change.
Some
viruses only affect one type of being, say, birds. If a virus that normally
affects birds does by chance enter a human, and if it picks up some human DNA,
this can produce a new type of virus that may be more likely to affect humans
in future. This is why scientists are concerned about rare viruses that spread
from animals to people.
Viral diseases
Viruses
cause many human diseases. These include:
- smallpox
- the
common cold and different types of flu
- measles,
mumps, rubella, chicken pox, and shingles
- hepatitis
- herpes
and cold sores
- polio
- rabies
- Ebola
and Hanta fever
- HIV,
the virus that causes AIDS
- Severe
acute respiratory syndrome (SARS)
- dengue
fever, Zika, and Epstein-Barr
- Some
viruses, such as the human papilloma virus (HPV), can lead to cancer.
What are friendly viruses?
Just
as there are friendly bacteria that exist in our intestines and help us digest
food, humans may also carry friendly viruses that help protect against
dangerous bacteria, including Escherichia coli (E. coli).
Combating viruses
The
body defends itself through the deployment of T-cells, which attack the virus. When
the body's immune system detects a virus, it starts to respond, to enable cells
to survive the attack. A process called RNA interference breaks down the viral
genetic material. The immune system produces special antibodies that can bind
to viruses, making them non-infectious. The body sends T cells to destroy the
virus.
Most
viral infections trigger a protective response from the immune system, but
viruses such as HIV and neurotropic viruses have ways of evading the immune
system's defenses. Neurotropic viruses infect nerve cells. They are responsible
for diseases such as polio, rabies, mumps, and measles. They can affect the
structure of the central nervous system (CNS) with delayed and progressive
effects that can be severe.
Bacterial
infections can be treated with antibiotics, but viral infections require either
vaccinations to prevent them in the first place or antiviral drugs to treat
them. Sometimes, the only possible treatment is to provide symptom relief.
Antiviral
drugs have been developed largely in response to the AIDS pandemic. These drugs
do not destroy the pathogen, but they inhibit their development and slow down
the progress of the disease. Antivirals are also available to treat infection
with the herpes simplex virus, hepatitis B, hepatitis C, influenza, shingles,
and chicken pox.
Vaccines
Vaccinations
are generally the cheapest and most effective way to prevent viruses. Some
vaccines have succeeded in eliminating diseases, such as smallpox. Vaccination
is the most effective way to prevent viruses.
Virus
vaccinations consist of:
- a
weakened form of the virus
- viral
proteins called antigens, which stimulate the body to form antibodies that will
fight off future
infections
with the same virus
- live-attenuated
viruses, such as immunization for poliomyelitis
Live-attenuated
vaccines carry the risk of causing the original disease in people with weak
immune systems. Currently, vaccinations exist for polio, measles, mumps, and
rubella, among others. Widespread use of these vaccines has reduced their
prevalence dramatically.
Two
doses of the measles vaccine, for example, offer 97 percent protection against
this disease. The measles vaccine has achieved a 99-percent reduction in the
incidence of measles in the United States (U.S.). If there is an outbreak, it
usually affects people who are not vaccinated.
Some
people choose not to vaccinate their children, and because most people around
them do vaccinate, the risk of getting measles is low. However, if fewer than
92 to 95 percent of people receive the vaccine, a community can lose its
"herd immunity," and an outbreak can occur. The risk of disease
increases dramatically.
In the
words of the CDC: "Antivaxxers help breathe new life into old
diseases." This can also affect vulnerable people who are unable to
receive the vaccine for some reason, such as a compromised immune system. Viral
infections usually resolve without treatment, but medication can relieve
symptoms such as pain, fever, and cough.