38 | New Scientist | 29 February 2020
with no known conditions for traces of
Perron’s retrovirus and discovered an active
form of the virus in 12.5 per cent of the general
population. She also tested 39 people with MS
and found it in every one of them. Brain tissue
from people who had MS when they died also
revealed the presence of retroviral protein.
“It was just incredible to see,” says Dolei.
“If we can be aware of what’s actually going
wrong in neurons, we can potentially change
how MS is treated.”
Dolei couldn’t initially determine whether
Perron’s retrovirus was a cause of MS or a result
of the disease process. But as she followed
patients over time, she found that the amount
of virus in the blood predicted the disease’s
progression and severity. What’s more, the
response to MS drugs and remission of
symptoms correlated with reduced levels
of retroviral proteins in the blood and the
cerebrospinal fluid surrounding the brain
and spinal cord. This suggested that HERV-W
might somehow be playing a role.Frankenstein’s molecules
By the time that young man walked into Nath’s
HIV clinic in 2005, evidence was also mounting
for the role of HERV-W in schizophrenia. Håkan
Karlsson, now at the Karolinska Institute in
Stockholm, had identified traces of a retroviral
protein called pol in the cerebrospinal fluid
of about a third of people he examined
who had been recently diagnosed with
schizophrenia. Again, the source seemed
to be the individuals’ own DNA.
As a retrovirologist, Nath had heard of
Karlsson’s work, and, suspecting that his
patient’s symptoms may have a similar cause,
he approached Jeffrey Rothstein, an ALS expert
who worked in a neighbouring lab. They
started to examine brain tissue from 28 people
who had had ALS when alive, and they detected
RNA from a retrovirus called HERV-K in every
single one. It was compelling evidence for the
role of retroviruses in ALS, but still didn’t prove
causation. Nath couldn’t rule out that dying
nerve cells may have activated the virus.
It was similarly unclear how such activation
might be contributing to nerve cell damage
in schizophrenia or MS. The baton was picked
up by Küry, who had been studying the
cascade of events leading to the degeneration
of nerve cells in MS. Küry realised that the
evidence for HERV-W contributing to MS was
circumstantial at best. “The question in MS is
always what comes first,” says Küry. “There
has to be some trigger that sends the body
towards an autoimmune response, but noone understands how this happens.”
Küry realised that he would have to look
at how HERV-W interacts with neighbouring
brain cells. Using brain tissue from deceased
MS patients, Küry and his colleagues showed
that a HERV-W protein called ENV activates
brain-based immune cells called microglia,
which not only directly damage neurons,
but also interfere with their repair. “Now that
we’ve identified a protein, we can start to think
about how to neutralise it with an antibody,”
says Küry, who published the results last year.
Although in some people with MS the body
might be synthesising proteins from HERV-W
and other endogenous retroviruses, Karlsson
stresses that individuals aren’t producing a
fully functional virus that can infect other
people. Rather, it is something about the
proteins produced and the body’s response to
them that is the problem. In small studies of
people with schizophrenia, scientists found
slightly elevated levels of an inflammatory
molecule called C-Reactive protein. This could
indicate that, in some people, the immune
system is responding to a virus. Karlsson still
doesn’t know whether this is the result of
endogenous retroviruses or how it might
contribute to the condition.
Despite mounting evidence for the role of
retroviruses in common illnesses, questions
remain. For one thing, it is still unclear what
proportion of MS, ALS and schizophrenia“ Studies suggest that
our cells may be less
able to keep these
viral elements
suppressed during
times of stress”
Viral hitch-hikers
Ancient retroviruses hidden in our genomes can reawaken
and contribute to conditions like multiple sclerosisPROTEINSTRESSVIRAL PROTEINA retrovirus inserts a copy
of its genome into the
DNA of cells it infectsIf the retrovirus infects sperm
or egg cells, the viral genome
can be passed to offspring and
successive generations,
potentially for millions of yearsOur cells work hard to keep viral genes inactive by
preventing their translation into proteins. As long as
they remain switched off, they don’t cause problemsStress or other infections can lead
to activation of some viral genes
and a synthesis of their protein
fragments. For example, synthesis
of the ENV protein may lead to
neuron damage, triggering MS