How Zombies Can Help Prevent the Next Pandemic

Incomplete viral genomes can quell disease and, with further

research, could be turned into treatments

Most people know of some of the tools that help us fight pandemics: safe and
effective vaccines, antiviral and antibody treatments, and for respiratory
infections such as COVID, public-health measures such as masks. But they
have overlooked one tool that might help us prevent the next pandemic:
zombie viral genomes.
Zombie viruses are the crippled byproducts of viral infection that can’t
reproduce without help. They are intriguing from a therapeutic perspective
because they seem to do several things to lessen disease: they prompt the
immune system to act, and, without adding to disease themselves, they suck
up some of the machinery that their active counterparts use to copy
themselves during an infection. They also cloak themselves in proteins that
normally wrap around viral genomes, resulting in viruslike particles that can
tag along when their operational counterparts spread. A better
understanding of how these zombies work could allow researchers like me to
engineer zombies as treatments so that when the next pandemic virus hits,
we can give people medicinal zombies to keep them from getting really sick.

Viruses multiply by replicating themselves with lightning-fast speed inside

the cells they infect. For the viral machinery that makes copies of the virus’s
genome that get packed into new particles, however, this speedy production
can be glitchy. This is often because the machinery lacks a proofreading
mechanism that scans that copied genome for mistakes, but even the viruses
that can proofread make mistakes. When these glitches happen, the
machinery introduces mutations, like ones that gave rise to highly
contagious SARS-CoV-2 variants such as Delta and Omicron. But even bigger
gaffes often occur, creating zombie genomes that lack the replication or
packaging functions a virus needs for productive infection. So when the
zombie genome is packaged and that crippled viral particle enters a healthy
host cell, it appears dead, unable to copy itself and make new zombies.
But when a zombie viral genome is delivered into a cell that is already
infected by a fully functional virus, then—like a zombie—it can spring to life.
It does this by diverting the viral machinery of functional viruses to replicate
itself, making virus-like zombies that can grow and spread, often at the
expense of infectious virus. So, the zombie infects, co-opts the replication
machinery of active viruses like a parasite, and at a minimum, seems to not
make the ongoing viral illness worse.
Take the influenza virus, for example. Molecular virologist Ana Falcón at the
National Center for Biotechnology in Spain has found links between zombie
viral genomes and the severity of disease. People who carried more influenza
zombie genomes avoided intensive care units, while those who carried fewer
zombie genomes suffered from more severe disease, sometimes ending up in
the hospital and dying. Having more zombie genomes can trigger protective
immune responses, leading to less severe disease.
Zombie viral genomes associated with other respiratory infections are also
linked to disease severity, but the outcomes can be good or bad.
Immunologist Carolina López at Washington University in St. Louis showed
that the presence of zombie viral genomes early in respiratory syncytial virus
infection, during the first three days of a one- to two-week infection, was
linked to overall lower virus levels and less severe disease. Yet the prolonged
presence of zombie viral genomes, beyond six days of infection, has been
associated with higher overall virus levels, greater activation of immune
responses, and greater severity of disease. Together, these results indicate
potentially complex roles of zombie viruses in the severity of disease,
depending on their effects on both virus production and immune activation.
What about zombies of SARS-CoV-2, the RNA virus that causes COVID? By
now, researchers have genetically analyzed countless nasal swabs from
people with COVID across the globe to reveal Delta, Omicron and many other
variants. But to make these discoveries, the researchers have sequenced full-
length RNA genomes; defective or incomplete viral genomes can complicate
analyses, so they are typically ignored or discarded. For us zombie virus
researchers, these defective genomes are a goldmine.
Genomics expert Chia-Lin Wei of the Jackson Laboratory in Connecticut has
discovered several hundred candidate zombie viral genomes occurring in
swabs from people with COVID. Some zombie genomes carried deletions
that were linked exclusively to either symptomatic or asymptomatic COVID.
Disease symptoms like tissue inflammation can be linked to cell-level
defenses that trigger virus-producing cells to kill themselves, so zombie
viruses that fail to trigger such defenses also fail to cause inflammation, and
their infections are asymptomatic. For viruses, the ability to cause mild or
asymptomatic disease can be beneficial, allowing its human hosts to go about
their daily interactions with others and more widely spread the virus.
For now, such observations raise more questions than answers. How do
zombie viruses of SARS-CoV-2 arise, and how do they affect the severity of
COVID-19 in individual people? What roles will zombie viruses play in the
behavior of the current pandemic in the coming months or years? More
broadly, what roles might zombie viruses play in diseases caused by other
viruses that could cause pandemics, like Ebola, influenza or Zika? And how
might we harness zombies to protect against future pandemics caused by
novel viruses?
Given the protection zombie viruses might provide, it’s reasonable to think
they could help treat COVID-19 or other infection by future pandemic
viruses. Virus expert Leor Weinberger of the University of California, San
Francisco, has recently engineered zombie particles of SARS-CoV-2 and
showed their protective effects against infection in hamsters. Importantly,
zombie particles suppressed the severity of COVID-like disease when given
before or after infection. Longer-term studies showed such particles might
protect against variants like Delta, Omicron or others. Finally, virologist Raul
Andino, also at U.C. S.F., has discovered that poliovirus zombie genomes can
stimulate mouse immune responses and protect those infected from catching
not only poliovirus, but also influenza and SARS-CoV-2.
These findings provide exciting evidence for the holy grail of vaccine
development: broad protection against diverse viruses. To grow and spread,
all viruses re-program their host cells to make virus proteins; infected cells
respond by activating defenses to slow or stop making those proteins.
Viruses escalate the arms race by inhibiting the signals cells used to slow or
stop making proteins. The recent studies in mice suggest how zombie
genomes may ultimately give the upper hand to the cells, shutting down
production of proteins viruses need to grow and spread.
If zombie genomes can stimulate protective immune responses in not only
mice but also humans, a single dose might someday protect us from new
variants of influenza virus, coronavirus or other viruses. More safety and
 efficacy studies will be needed to assess the capacity of engineered zombie
particles to treat or prevent disease before they can be considered for human
use. For now, zombie viruses offer an interesting new idea in protecting us
against future pandemics.

Essential words for writing and speaking

1. Quell (v) - to completely stop or end something:
The police were called in to quell the riot.
2. Overlook (v) - to fail to notice or consider something or someone:
I think there is one key fact that you have overlooked.
3. Cloak (v) - to cover or hide something:
He has always kept his love affairs cloaked in secrecy (= kept them
secret).
4. Glitchy (adj) - often experiencing small technical problems or faults:
A glitchy sound system completely ruined the concert.
5. Crippled (adj) - damaged and unable to move or operate effectively:
A crippled submarine found itself unable to surface.
6. Co-opts - to include someone in something, often against their will:
Whether they liked it or not, local people were co-opted into the victory
parade.
7. Severity (n) - seriousness:
Even the doctors were shocked by the severity of his injuries.
8. Goldmine (n) - something from which a person, company, etc. can earn
a lot of money or that can provide a lot of something that people want:
Manufacturers of computer-aided design systems are competing to take
advantage of this potential goldmine.
9. Novel (adj) - new and original, not like anything seen before:
Keeping a sheep in the garden is a novel way of keeping the grass short!
10. Reasonable (adj) - sensible and fair:
We believe that our audits provide a reasonable basis for the opinion
expressed above.