29 February 2020 | New Scientist | 39against other retroviruses: the resurrected
fossils in our genomes. He is now recruiting
people for a small pilot study to test whether
giving a cocktail of three antiretroviral drugs
is beneficial to people with ALS who don’t
have HIV and who have high levels of HERV-K
activity. A recent study suggests that this group
may comprise a fifth of people with ALS.
Meanwhile, Hammell has used machine
learning to analyse gene activity in brain cells
from recently deceased ALS patients. Her
analysis, published in October 2019 in Cell
Reports, identified three subtypes of ALS,
one of which was dominated by hidden
viruses in the genome.
Possibly the biggest advance has come
from a Swiss pharmaceutical company called
GeNeuro, which Perron established in 2006
to develop new treatments for MS based on
targeting retroviral proteins. GeNeuro is
testing a drug called temelimab, which binds to
the ENV protein from HERV-W and triggers its
destruction. The results of a trial in 270 people
with MS, presented at a scientific conference
last September, suggests that the drug slows
the shrinkage of brain tissue by 40 per cent.
This is one of the most destructive
consequences of the disease, and may be
what leads to irreversible neurological and
cognitive impairments. With existing MS
therapies doing little to slow disease, Dolei
says temelimab represents a huge advance.
The company has also begun testing
temelimab in people with type 1 diabetes,
another autoimmune condition, caused by the
destruction of insulin-producing beta cells in
the pancreas. The move comes after a 2017 study
identified HERV-W activity in the pancreatic
cells of about half of a group of people with
type 1 diabetes. And the firm is working on
antibodies to treat ALS and certain types of
psychosis related to schizophrenia that have
also been associated with retrovirus activation.
It is early days, but the development of such
drugs could transform the war that has been
raging between us and viruses since our
earliest beginnings. “Our cells have been
fighting these things over evolutionary time
scales – battles they have mostly won, in the
sense that we are still here,” says Hammell.
With the drugs on our side we may win another
important victory against the invisible
enemies hidden in our genomes. ❚caused by infection with the Epstein-Barr
virus – as teenagers or young adults. Possibly,
the infection triggers changes in DNA folding
that leave some previously buried viruses
exposed, prompting them to stagger to life like
molecular versions of Frankenstein’s monster.
In the case of people with HIV, their weakened
immune systems may be less able to spot and
destroy cells containing reactivated viruses.Internal warfare
All humans have these fossil viruses in our
DNA, and we all age and experience multiple
infections, yet most of us will never develop
MS, ALS or schizophrenia. Küry hypothesises
that a combination of virus reactivation and
a genetic predisposition is required to lead to
illness. This may be bad news for individuals,
but the reactivation of these clandestine
viruses may also create the perfect Achilles’
heel in some of the conditions they cause.
As an HIV doctor in the late 1980s and
early 1990s, Nath had a front-row seat to the
lifesaving power of antiretroviral drugs. He
prescribed them to all his patients – including
the young man with ALS. That the drugs
decreased the amount of HIV in the man’s
blood and boosted his T-cell counts was no
surprise to Nath. But the rapid improvement
of ALS-like symptoms in people with HIV
hinted that these drugs might be effectiveCarrie Arnold is a science
writer based in Virginiacases are related to the reactivation of these
ancient viral stowaways. Their existence also
doesn’t rule out other potential causes.
Another question is how we can carry copies
of the viruses without feeling major ill effects.
If HERV-W is thought to be buried in all our
genomes, why does it only wake up and start
causing problems in some people?
Our cells work hard to prevent these viral
genes from being translated into proteins. The
cell twists DNA into a complicated 3D snarl, and
its protein-making machinery can only access
genes on the surface of this tangle. As long as
the hidden viruses remain buried in the
middle, they are effectively silenced. And if
that isn’t enough, the body has proteins whose
main job is to suppress the production of any
endogenous retroviral proteins. The slow
accumulation of genetic mutations over time
adds an additional layer of protection as they
often render the viral proteins non-functional.
However, these fail-safes aren’t perfect, and
studies suggest that our cells may be less able
to keep these elements suppressed during
times of stress. “When a cell is in crisis, it can
make mistakes,” says Molly Gale Hammell, a
geneticist at Cold Spring Harbor Laboratory in
New York. One such source of stress is infection
with another virus.
Dolei notes that a disproportionate number
of her MS patients report having experienced
glandular fever (infectious mononucleosis) –