MCB55 Midterm #2, Modules 1-3

MCB55 UC Berkeley

Coronavirus, rabies, ebola

Some zoonotic diseases

HSV1, HIV, HBV, HCV, HPV

Forever viruses/Viruses and Cancer

Viruses can infect

all types of lifeforms

1 virus associated with it

Every living organism studied to date has a least

wherever there is life

viruses exist

8% virus

our genome is

increasing in numbers

RNA viruses are increasing in numbers

Syncytin - 1

a endogenous retroviral envelope protein that has retained its original fusogenic properties and participates in trophoblast fusion and the formation of a syncytium during placenta morphogenesis

What is a virus

An infectious, obligate parasite comprising genetic
material (DNA or RNA) surrounded by a protein coat
and/or an envelope derived from a host cell membrane

Protein shell

protects genome of virus

envelope (lipid membrane)

Makes it so things can’t get inside the envelope (Vaccines against these viruses are made against the envelope)

attachment

Envelope proteins are responsible for

retroviruses tend to be

envelope viruses

with 2 phases

a virus is an organism with

virion

phase before the virus enters a cell

Infected cell

phase where the virus releases genome, it gets replicated, and then the virus puts itself back together

1. Attachment
2. Penetration
3. Uncoating
4. Replication
5. Assembly
6. Release

Stages of a viral infection

Attachment Stage

Spike protein attaches to receptors, Starts endocytosis

Hundreds of progeny visions can be produced from a single infectious particle

One infected cell can give rise to thousands of viruses

reproduce and spread

A virus's fitness, or success, depends on its overall ability to

making people sick (ex: coughing and sneezing)

can reproduce and spread by

HHV - 7

• infects babies

• rashes

• nearly all children are infected by age 6

• once infected they are infected for life

Gene Therapy

Viral vectors (AAVs, lentiviruses) deliver therapeutic
genes. Clone viruses (modified to not be pathogenic), Hopefully these genes will integrate into the system and replace bad genes

Cancer Therapy

Oncolytic viruses kill cancer cells and boost immune
responses.

Phage Therapy

Bacteriophages target drug-resistant bacteria

Vaccines

Live-attenuated, inactivated, viral vector.

Neuroscience

Viral tracers map brain circuits which can detect rabies and herpes

Molecular Biology

Viruses revealed DNA/RNA processes; retroviruses led to the discovery of oncogenes (Genes that trigger cancer)

Genetic Engineering

Viral vectors deliver CRISPR/Cas9 used in model organisms to discover genes

• Viruses have some of the smallest genomes

• Circoviruses have the smallest genomes (Only 2-3 genes)

Viruses have about 1 million times less genetic information than the genomes of most plants and animals they infect

a lot

Viruses mutate

The more viruses mutate

the smaller their genome is

mutations

replicating a lot leads to more

very unstable

a lot of replicating and mutating makes viruses

polymerases

Mutations are controlled by

helpful

mutations can be

1

How many mutations doe RNA viruses make every time they mutate?

• Neutral

• Advantageous

• Deleterious

The phenotype of the mutation can be

protein capacity

Change in amino acid can change

neutral or harmful

Most mutations are

Immune escape mutation

evade recognition by antibodies and T cell (Need modified vaccines to combat these mutations)

SARS COV-2

What virus has an immune escape mutation?

Increased Spread mutation

mutations can enhance transmissibility (Gives more chance for replication)

Drug Resistance mutation

survive antiviral treatments

New Hosts/Cell mutation

expand host range or infect new tissues

SARS COV-2

• Bats -> humans

• Needed to mutate to replicate better in humans

Example of New Hosts/Cell mutation

Replication benefits mutation

can adapt to different evironments

Some of the host population will escape 

• Leads to virus adapting and mutating to catch the host next time

• Then host mutates to become better and escape again

• Cycle repeats

An evolutionary view of the arms race between host and pathogen

The red queen hypothesis

Constant co-evolution: It takes all the running you can do, to stay in the same place

Model error of catastrophe

The more mutations the more chances that genomes are dead

Zoonoses

infectious diseases that can be transmitted from
vertebrate animals to humans under natural conditions

Spillover

The event where a pathogen jumps from an animal to a human

60%

What percentage of known infectious diseases are spread from animals?

Significant morbidity and mortality + Impact on regional/global economies

zoonoses have

Zoonoses can be

• be stably established in animal populations, and transmit from animals to people with little or no subsequent person-to-person transmission. For example (West Nile virus
  or Rabies virus)

• Spread efficiently between people once introduced from an animal reservoir, leading to epidemic (eg, Ebola virus) or pandemic spread (eg, pandemic
  influenza, coronaviruses)

• be bacteria

vector (ex: mosquitoes)

Viruses can be transmitted to a ______ and then humans can become infected via the ______

more humans will become infected

once a zoonosis reaches a human once it likely that

are still zoonotic

viruses that follow the pattern of diseased animal -> vector -> human

Zoonotic transmission

• Fecal, Oral (Hantavirus)

• Inhalation (Coronavirus)

• Contact with body fluids (Nipah virus)

• Penetrating wounds (Rabies)

• Vector transmission (West Nile virus)

Reverse Zoonoses

• Sars cov-2 has been detected in 25 animal species because of humans

• Animals who contracted a disease from humans can transfer a new mutated version back to humans

Nipah Virus

A zoonotic virus transmitted from fruit bats (sometimes pigs) to humans, causing severe respiratory illness and encephalitis. It can also spread through contaminated food or direct contact with infected individuals. 40-100% death rate

encephalitis

Brain infection, Many people die from this (those who don’t suffer long-term brain damage)

symptomatic

Most cases of Nipah virus are

respiratory involvement or respiratory illness alone, which can
progress to acute respiratory distress syndrome.

Some people with Nipah virus infection
have

nets to prevent bats from getting into palm sap and water supplies

low-tech solution to Nipah virus

The One Health Challenge

• Human health is closely linked to animal and environmental health

• No single sector can tackle zoonotic risk alone

• Public health interventions require collaboration

Reservoir Host Distribution & Interactions

• Geographic range overlap
• Travel and trade
• Hunting and bushmeat consumption
• Market exposure (wild animal meat)
• Loss of biodiversity
• Land use changes, deforestation
• Climate change is altering host and pathogen dynamics

• Immunological variation
• Genetic susceptibility
• Behavioral practices

Things that can expose people to viruses

• Second most diverse mammalian order

• Large, gregarious colonies → rapid pathogen transmission

• Large population sizes sustain infections

• Frequent human interactions

Why are bats a common zoonosis reservoir?

Second most diverse mammalian order

• Since they are mammals they are close to us genetically

• Allows for easier adaptation

Large gregarious colonies -> rapid pathogen transmission

Close contact allows for easier spread

Frequent human interactions

• Peridomestic habits

  • Like to live in abandoned places

• Bushmeat consumption

  • Sometimes sold in markets

• Habitat loss/deforestation

  • Due to less space they are moving closer to human civilization

long lifespans, long-distance travel (flight), immune system differences

Unique Biological features that make bats good reservoirs

Immune system differences

• Very well adapted to viruses

• Can contract a pathogen and not become sick (True for many pathogens)

• Dampened cytokine storm

• Constant innate activation

Viruses in bats

By extracting blood from bats they can find out what a bat is diseased with (ex: Rabies, Herpes, Coronavirus) (most bats don’t appear sick while infected)

Most animal viruses fail to infect human

• Extreme bottleneck in emergence

• Requires overcoming major obstacles

• Our bodies are often able to get rid of animal viruses bc they are meant for another species (Bad or no replicating in humans)

• If you get a disease from an animal it doesn’t mean one human can transfer it to another human

requires viruses to be able to interact with cellular proteins

Once inside a host, replicating and spreading is a complex process for a pathogen because it

1. Attachment
2. Penetration
3. Uncoating
4. Replication
5. Assembly
6. Release

There are many steps all involving interactions with host proteins

• A virus needs to interact with many different cellular proteins in order to enter a new cell and replicate

• has to evade immune responses

What are the obstacles to overcome to replicate in a new host?

Viral sensing and Interferon pathways (antiviral state)

What immune responses do zoonotic diseases need to evade?

viral sensing

• Cells monitor their extracellular space and intracellular space for the presence of atypical nucleic acid (wrong location or unusual structure) associated with viral infection

• Can detect cytosolic DNA, double stranded RNA, unusually capped mRNA, and more

• Upon sensing it only takes a few minutes for defense to start

cytosolic DNA

some sort of infection is bringing the DNA out of the nucleus (Once noticed defenses are enacted)

Interferon pathways (antiviral state)

• Play a critical role in control of viral infections

• Often on the exam

• Freshly infected cell sends notice to other cell that there is an infection so that when the infection spread to it it has built up antiviral proteins to kill the virus

inhibit the IFN response

To replicate within a host, viruses need to

dsRNA (replicating genome

Hiding _____ is one strategy used by viruses to prevent being detected and eliminated (ex: VP35 protein in ebola)

VP35

associates with dsRNA to prevent recognition by intracellular sensors

• use different cell surface receptors
• escape a novel type of immune response
• ensure they are transmitted by the new host

Often, pathogens must adapt to successfully infect a novel host

high mutation and multiplication rates

Among the pathogens, RNA viruses might be the most likely to be associated with spillover events because they have