Sample Questions

Biothon-Academic Marathon in Biology

The Secret Social Lives of Viruses

Geneticist Rotem Sorek could see that his bacteria were sick — so far, so good. He had
deliberately infected them with a virus to test whether each ailing microbe soldiered on alone
or communicated with its allies to fight the attack. But when he and his team at the Weizmann
Institute of Science in Rehovot, Israel, looked into the contents of their flasks, they saw
something completely unexpected: the bacteria were silent, and it was the viruses that were
chattering away, passing notes to each other in a molecular language only they could
understand. They were deciding together when to lie low in the host cell and when to replicate
and burst out, in search of new victims. It was an accidental discovery that would
fundamentally change scientists’ understanding of how viruses behave.

Viruses that infect bacteria — spiky lollipop-like creatures known as bacteriophages [1] (or
phages) — have surveillance mechanisms that bring them intel on whether to stay dormant or
attack, depending on the availability of fresh victims. But researchers long thought these
processes were passive; the phages seemed to just sit back and listen in, waiting for bacterial
distress signals to reach fever pitch before taking action. Sorek and his colleagues had found
phages actively discussing their choices. They realized that as a phage infects a cell, it
releases a tiny protein — a peptide just six amino acids long — that serves as a message to its
brethren: “I’ve taken a victim”. As the phages infect more cells, the message gets louder,
signaling that uninfected hosts are becoming scarce. Phages then put a halt to lysis [2] — the
process of replicating and breaking out of their hosts — instead of staying hidden in a
sluggish state called lysogeny [3].

The viruses, it turns out, did not depend on bacterial cues to make their decisions. They
controlled their own destiny. “This finding was a big, important, revolutionary concept in
virology,” says Wei Cheng, a structural microbiologist at Sichuan University in Chengdu,
China. Sorek named this viral peptide ‘arbitrium’, after the Latin word for decision. It seemed
to work much like the communication system used by bacteria — quorum sensing [4] — to
share information about cell density and adjust the population accordingly. Yet it was the first
time anyone had demonstrated molecular messaging of this kind in viruses. And it fitted into
an emerging picture of viruses as much more sophisticated social agents than scientists had
given them credit for.

Virologists have long studied their subjects in isolation, targeting cells with just a single viral
particle. But it’s become increasingly clear that many viruses cooperate, teaming up to
co-infect hosts and break down antiviral immune defenses. The implication is that researchers
might have been going about their experiments all wrong. Learning the language behind these
viral interactions could inform the design of new treatments for cancer and nasty
superinfections. The social predilections of viruses even help to explain how they evade the
bacterial immune system known as CRISPR.

Figure 1 - The Secret Social Lives of Viruses

Social studies
Scientists first spied viruses mingling in the 1940s, when separate experiments showed that
two viral particles could simultaneously invade the same cell and swap genes. But these early
observations were only really interesting to scientists as an experimental method — they
allowed researchers to create a cross between two viral strains. The relevance to basic biology
was missed. It wasn’t until 1999 that anyone took any notice of what cooperation achieved for
the viruses themselves. That year biologists showed that phages play their own version of the
prisoner’s dilemma strategy game, working in partnership under certain circumstances and
acting in their own self-interests in others.

Figure 2 - Viruses Known as Phages (Green) Can Better Infect Cells like This Bacterium (Orange)
when They Cooperate and Communicate.

Other examples of beneficial viral interactions followed, including ones that involved the
pathogens responsible for diseases such as influenza. They often took place between different
viral strains that had a shared interest in boosting their own reproductive chances. But the
molecular basis of those cooperative traits — the method of communication — had largely
remained elusive. That’s why the arbitrium discovery was such a big step forward for the field.

A microbiologist showed that the receptor for arbitrium in the phage can interface not only with
genes in the bacterium that help the virus to reproduce but also with other, unrelated stretches of
DNA. That means that its activity might not be limited to the virus’s stay-or-go decision. The
researchers are now exploring whether the phage’s peptide language alters the activity of key
genes in its victim, too. Expanding on his own initial discovery, Sorek has found arbitrium
peptides popping up everywhere. His team has now found at least 15 different types of phage,
all of which can infect soil microbes and use some sort of short peptide to communicate. The
viral chit-chat thus seems to have evolved to allow communication only between close relatives.
Phages might speak only to their own kind, but they can also listen in on other languages.
Molecular biologists have found that viruses can use quorum-sensing chemicals released by
bacteria to determine when best to start multiplying — and murdering.

For the greater good

Some viral cooperation seems to verge on altruism [5]. Two independent groups reported last
year that some phages act selflessly to overcome the viral countermeasures of Pseudomonas [6]
bacteria. Take vesicular stomatitis virus (VSV), which mainly infects farm animals, but can
cause a flu-like illness in humans, too. Particles of this viral pathogen suppress host immunity
at a personal cost but at a benefit to the group. No one is sure yet how this cooperative evasion
is happening, but the work highlights how crucial altruism can be for the success of VSV. That
could help scientists to beat the virus in farm animals, and optimize it for use in vaccines and
therapeutics.

Other instances of collective action are widespread among disease-causing viruses. In

poliovirus, for example, multiple genetically distinct viral strains can clump together to swap
gene products and enhance their human-cell-killing potential. And two strains of influenza —
one that excels at cell entry, the other at cell exit — grow better when maintained in cell culture
together than when kept apart. That is, unless the destructive power of viruses could be used for
good. Several groups are testing phages as a treatment for bacterial infections — and knowing
more about how they converse with each other could help to refine such therapies, which have
a long history in medicine but are only just starting to be manipulated for therapeutic gain.

Engage the phage

Last month, for instance, researchers described the first successful clinical use of genetically
engineered phages to tackle a drug-resistant bacterial infection. For infections such as this, of
course, the ideal solution is to use the virus to annihilate [7] the bacteria entirely. But for
conditions that are marked by a microbial imbalance, such as acne [8], some types of cancer,
and inflammatory [9] bowel disease, it might be better to deploy a phage that can help to restore
the balance without an all-out assault. And for those more subtle applications, knowing exactly
how viruses communicate could be really useful for helping us to engineer phages that could be
used for treating disease. Tapping into the arbitrium system could thus lead to more tractable, or
even reversible, treatments. The engineered microbes could one day be used, for instance, to
deliver medicines in precise doses or to specific locations.

Notes:
[1] Bacteriophage: a virus that is parasitic in a bacterium and multiplies within its host, which
is destroyed when the new viruses are released.
[2] Lysis: the destruction or dissolution of cells by the action of a particular lysin.
[3] Lysogeny: the biological process in which a bacterium is infected by a bacteriophage that
integrates its DNA into that of the host such that the host is not destroyed.
[4] Quorum sensing: a system of stimulus and response correlated to population density.
Many species of bacteria use quorum sensing to coordinate gene expression according to the
density of their local population.
[5] Altruism: is unselfish concern for other people's happiness and welfare.
[6] Pseudomonas: any of a genus of rodlike Gram-negative bacteria that live in soil and
decomposing organic matter: many species are pathogenic to plants and a few are pathogenic
to man.
[7] Annihilate: to annihilate something means to destroy it completely.
[8] Acne: if someone has acne, they have a skin condition that causes a lot of pimples on their
face and neck.
[9] Inflammatory: an inflammatory condition or disease is one in which the patient suffers
from inflammation.

1. Virions have no cellular structure but are composed of DNA and RNA inside and protein
outside.
A. True
B. False

2. One of the revolutionary concepts in virology is that viruses rely on clues from bacteria to
make decisions.
A. True
B. False

3. A six-amino-acid peptide transmits information when a phage infects a cell, while a phage
infects more cells by secreting more.
A. True
B. False

4. What is a virus that infects bacteria called?

A. Arbitrium
B. Bacterium
C. Bacteriophage
D. Pseudomonas

5. Which components are NOT needed to form new virions?

A. Nucleus
B. DNA
C. RNA
D. Protein

6. In order to survive and reproduce, the virus must ______ a cellular host and parasitic.
A. kill
B. infect
C. evade
D. divide

7. How does the Baltimore system classify viruses?

A. By their shape
B. By their properties
C. By their structure
D. By their genomes

8. What can be explained by the social preferences of viruses?

A. How viruses evade the bacterial immune system.
B. Why viruses evade the bacterial immune system.
C. When viruses evade the bacterial immune system.
D. Where viruses evade the bacterial immune system.

9. What is the function of phage surveillance mechanisms?

A. Providing information based on the size of the bacteria and determine only their
dormancy.
B. Providing information based on the environment and growth of the bacteria.
C. Providing information based on the type of bacteria and determine only their attack.
D. Providing information based on the availability of bacteria and determine their behavior.

10. Arbitrium receptors in bacteriophages bind not only to the genes in bacteria that help the
viruses ______, but also to other bits of DNA that are not related.
A. mutate
B. transfer
C. survive
D. multiply

11. What does quorum sensing do?

A. It adjusts the cell density according to the information of the population.
B. It adjusts the population according to the information of cell density.
C. It shares information about the cell population and adjusts the cell density.
D. It shares information about the cell population and cell density.

12. How can humans exploit the altruistic behavior of viruses?

A. We can use it to kill viruses in animals and to research vaccines.
B. We can use it to determine how the cooperative avoidance behavior of the virus occurs.
C. We can use it to understand the success of altruism in vesicular stomatitis virus.
D. We can use it to treat the flu-like illness that VSV causes in humans.

13. What’s the point of learning the language behind viral interactions?
A. Helping us take advantage of bacteriophages to destroy all bacteria in the normal
microbiome and reduce the cost of treatment.
B. Helping us make the viruses in effect become programmable assassins that could be made
to kill off any bacterium.
C. Helping us design new therapies for diseases such as cancer and malignant infections by
providing some effective information.
D. Helping us get bacteria to attack viruses with specific proteins that can be designed to
disrupt cells’ CRISPR-based immune defenses.

14. Why is the discovery of arbitrium so significant for studying viruses?

A. Because arbitrium is the molecular basis for all viruses to communicate with each other,
and they can help us disrupt the cooperative and clustering of viruses.
B. Because arbitrium is important for the virus strain to increase its own reproductive
chances, and it can sense signals unique to other microbes.
C. Because before the discovery of arbitrium, researchers had not learned much about how
different viruses interact with each other.
D. Because the more we study how different viruses interact, the more we learn about
viruses, and that is important for us to understand viruses.

15. Which of the following statements is WRONG?

A. Genetically engineered phages can be used to treat bacterial infections, but they can also
help regulate the body's microbial imbalance.
B. Bacteriophages have a long history in medicine as a treatment for bacterial infections, and
researchers hope to use them with more precision in the future.
C. The language between phages is rich but limited, and at some critical moments in
determining their fate, the role of language between phages is particularly important.
D. Scientists have long known that viral strains that cluster together exchange genes, but
because the experiments are done in isolation, the results are less objective.
Answers:
1. B
2. B
3. A
4. C
5. A
6. B
7. D
8. A
9. D
10. D
11. B
12. A
13. C
14. C
15. D