MCB 55 Plagues and Pandemics Midterm 2

COSCOY 2024 Fall Berkeley

CORONAVIRUS BINDING ASSEMBLY ORDER

First

Bind and viral entry

CORONAVIRUS BINDING ASSEMBLY ORDER

Second

Release of viral Genome

CORONAVIRUS BINDING ASSEMBLY ORDER

Third

Replication of viral genomic RNA

CORONAVIRUS BINDING ASSEMBLY ORDER

Fourth

Transcription of Viral RNA

CORONAVIRUS BINDING ASSEMBLY ORDER

Fifth

Translation of viral proteins using host machinery

CORONAVIRUS BINDING ASSEMBLY ORDER

Sixth

Assembly of viral particle

CORONAVIRUS BINDING ASSEMBLY ORDER

Seventh

Formation of mature vision

CORONAVIRUS BINDING ASSEMBLY ORDER

Eighth

Exocytosis

Name the 3 highly pathogenic viruses of CORONAVIRUS

SARS CoV1

SARS CoV2

MERS CoV

Name the 4 Mild upper respiratory dieases of CORONAVIRUS

HCOV-NL63

HCOV-229E

HCOV-OC43

HCOV-HKU1

What does the 19 in “COVID-19” mean?

the Corona Virus and the disease it causes were identified in 2019

name the anatomy of the CORONOVIRUS structure

Spike

Nucleocapsid

Membrane

Envelope

RNA Viral Genome

Symptoms of CORONAVIRUS during INITIAL week

Fever

Dry cough

sore throat

loss of smell & or taste

head/body aches

What is ARDS

(Acute Respiratory Distress Syndrome)

Fluid accumulates in the lungs’ air sacs causing breathing difficulties and low blood levels. Oxygen levels in blood drop so low that struggle to breathe

patients end up on ventilators, many die.

What is ACE2

(angiotensin converting enzyme 2)

Helps BP regulation

ACE2 is expressed throughout the body Does that account for some of the symptoms observed in Covid 19 patients

A widespread of ACE2 in Organs such as heart kidney brain lungs explains diverse symptoms seen in COVID 19 it uses ACE2 to infect and damage these tissues

ACE2 is expressed throughout the body Does that account for some of the symptoms observed in Covid 19 patients specifically Lungs

Pneumonia and ARDS

ACE2 is expressed throughout the body Does that account for some of the symptoms observed in Covid 19 patients specifically heart

Direct infection and inflammation

lack of O2 and formation of blood clots

ACE2 is expressed throughout the body Does that account for some of the symptoms observed in Covid 19 patients specifically Ileum

GI symptoms

Virus can be shed in feces

FUN FACT (Concentration of SARS COV2 in Wastewater Samples)

both A/symptomatic patients with COVID shed the virus in Poop. Prevalence of virus in wastewater treatment plant can be monitored to serve as early warning of Future COVID outbreaks and understand the efficacy of Public Health interventions

What is the estimated amount of Viruses in the Earth

1E31

what percentage of Ocean Microbes are destroyed each day by viruses?

20%

note: Viruses exist wherever there is life.. including the most inhospitable environment

What percent is our Genome for Viruses

8%

What is Syncytin-1

AN endogenous retroviral envelope protein that retains its fusogenic properties, aiding trophoblast fusion and Syncytium formation in placental development

What is a Virus

An infectious parasite made of genetic material (DNA or RNA) encased in a protein coat and/or a host cell membrane envelope.

What is the size of the Herpes Simplex Virus

~300nm

A virus is an organism with two phases. What are those phases?

Viron and Infected cell

Are Viruses alive

they are considered to be Non-living because they cannot reproduce or carry out metabolic processes without host cell.

No

What are the Stages of Viral Infection ?

1.) Attachment

2.) Penetration

3.) Uncoating

4.) Replication

5.) Assembling

6.) Release

True or False “Viruses have about 1 million times less genetic information than the genomes of most plants and animals they infect.”

TRUE the number is around 1K-1M nucleotide pairs

Viruses are mutating Does it matter?

YES

Affect transmissibility, virulence and the effectiveness of vaccines and treatments, potentially leading to new variants that may evade the immune response.

Fun Fact (Molnopiravir: coding for catastrophe)

Raised concern about the antivirus drug molnupiravir, risks: intro of errors in viral DNA that could lead to resistant variants or unintended consequences for human DNA, while emphasizing the need for caution evaluation of such treatments

What do Viruses do with only a little bit of genetic information?

1.) Take over cellular machinery and redirect it to mass production trial proteins. replicate the viral genomes.

2.) Avoid eradication by immune system

3.) keep the infected cell alive enough to complete its replication cycle

what is a zoonosis

infectious deceases that are transmissible from vertebrate animals to humans under natural conditions.

What is a spillover or Zoonotic spilloverI

The event where pathogen jumps from animal to human or vice versa

Is Dengue a Zoonosis

YES

Spread through bites of infected Aedes mosquitoes

What percentage of known infectious diseases are spread from animals.

60%

What are the 2 main abilities of Zoonotic Pathogens

1.) Be stably established in animal populations and transmit to people with little or no subsequent person-person transmission (WNV or rabies)

2.) Spread efficiently between people after introduction from animal reservoir leading to epidemic (ebola) or Pandemic (Flu or COVID)

What are the Zoonotic transmissions

Fecal/Oral (Hantavirus)

Inhalation (COVID)

Contact with body fluids (Nipah)

Penetrating Wounds (Rabies)

Vector transmitted mosquitoes and Ticks (West Nile virus)

What is Nipah Virus

Endemic to fruit bats in Southeast Asia which carry the virus and spread through bodily fluids such as saliva or urine.

Nipah

Asymptomatic (mostly)

(Symptoms): cause severe encephalitis, Repiratory illness, ARDS death rate (40%)

Contaminated food: Virus spread through consuming contaminated food or fruit products such as raw date palm juice.

Close contact: Spread through close contact body fluids (saliva urine blood feces). can happen when caring for infected person or when close proximity to someone infected `

Spatiotempral dynamics of spillover what 8 things must happen at the same time in order to be a spillover.

1.) Host Distribution

2.) Host Density

3.) Pathogen Prevalence

4.) Infection intensity

5.) pathogen release from host

6.) Survies and spreads

7.) exposition

8.) within host barriers

what are some animal host associated factors

bats as reservoirs of multiple viruses due to capacity of immune system of these animals to deal with a wide variety of pathogens

ecological habits of animals, sharing environment with humans and livestock and pets

some animals can act as intermediate hosts in spillover events.

3 Human host-associated factors

1.) immunological factos

2.) Genetic Factors

3.) Behavioral factors

When is the risk of a spillover the highest?

species among the same phylogenetic tree

animals with greater phylogenetic distance from humans more likely to host virus with increased virulence but limited capacity for human-human spread.

name bat-human transmissions that are known

Rabies, Ebola, Marburg, SARS COV 1 & 2, MERS COV, Nipah, and Hendra.

disease in human for Rabies

Acute fatal Encephalitis

disease in human for Ebola and Marburg

Hemorrhagic fever

disease in human for SARS COV 1&2 and MERS COV

Respiratory syndrome

disease in human for Nipah and Dendra

Encephalitis and Respiratory disease

disease in human for inFluenza

Respiratory tract infections

disease in human for Hantaan virus

Hemorrhagic fever

disease in human for Mammalian orthoreovirus

Enteric and Respiratory infections

What is special about bats?

2nd most diverse mammal order on earth, and social creatures.

facilitate rapid transmission of pathogens

large population sizes could sustain acute immunizing infections

Select for viruses that can adapt to novel hosts environment

Human interaction is frequent when looking at Periodomestic habits, Bushmeat and Deforestation.

Long lifespan

fly long distances allowing dispersal of diseases, and mimic fever when flying that whole time.

Weakened DNA sensing due to high metabolic requirement of flight

innate immune system is always on

What is the most extreme bottle neck in viral emergence?

Animal viruses not compatible with humans.

what are the 2 obstacles to overcome replication in new host

1.) needs to interact with many different cellular proteins in order to enter new cell and replicate

2.) needs to evade immune responses of host.

hundreds of viruses are know to infect humans. What fraction of these are able to evade interferon responses?

Only the ones that make us sick

What does a virus need to replicate in a host.

needs to inhibit the IFN response

What do pathogens do to adapt successfully and infect a novel host?

use difference cell surface receptors

escape a novel type of immune response

ensure they are transmitted by new host

Among the pathogens RNA viruses might be the most likely to be associated with spillover events because of ?

High mutation rates and High multiplication rates

What percentage is estimated to be non hospitalized cases

10-30 %

what percentage is estimated of Hospitalized cases

50-70%

what percentage is estimated of vaccinated cases

10-12%

What is the IN-Vitro transcribed mRNA formulated into lipid nanoparticle cycle

1.) Sequence Design

2.) Invitro transcription

3.) Purification

4.) nano precipitation

5.) Filtration

6.) mRNA Vaccine!!!

why was COVID Vaccine a huge success

It was released to the public after one year of trials and preclinical studies so it was given very quickly to the public.

What is the time frame to take the vaccine (Pfizer)

take dose 1, wait 4weeks to a month, dose 2, DONE!! Booster after 6 months if necessary.

what is the dominant variant of COVID 19

Delta Varient

When was rabies recognised as an infectious disease?

1804

What is Rabies virus

Species for the Lyssavirus genus (Rhabdoviridae family)

enveloped, RNA virus with a helical capsid

aprox 75-180nm long

How many kills does Rabies get per year

60K kills yearly

what animals can transmit rabies

Dogs, bats, raccoons, foxes. etc

almost all animals have chance to get rabies but which never transmit rabies?

Birds, Fishes, lizards

how does transmission for human happen for rabies?

Usually from bite or saliva contact

Rare: inhalation of virus containing aerosols or human-human transmission through transplantation.

how many deaths world wide of Rabies per year

~ 55K mostly in Africa and Asia

around how much percent of human cases caused by dog bites

~98%

FUN FACT: Vulture India Crisis

The Decline in vulture populations in India due to veterinary drug diclofenac, which is toxic to vultures that feed on treated carcasses. This decline caused ecological issues such as increased scavenger populations and spread of diseases like rabies, prompting conservation efforts to ban diclofenac and promote alternatives for livestock.

around 40M vultures in India now 19K. Feral dogs increased by 5M so around 38M people got bitten with the Rabies virus.

what percentage of all animal bites cases are reported to occur in children?

40-60%

in 1938 most cases of rabid animals were reported domestic (9.3K) and some were wild (44). Since then the numbers have reverse today..

around how many cases annually in the USA

1-3 cases per year with 25 being in the US in the past 15 years

what is the cost of annual rabies prevention

$300M

what are some ways to control rabies in Wildlife?

1.) Trap/Vaccinate/ Release (works with raccoons and often combined with oral baits)

2.) Oral baits with anti-virus (slowed outbreak in Ohio for raccoons and used in Texas for coyotes and foxes)

Rabies Pathogenesis after exposure

1.) BITE: saliva contamination

2.) Viral entry into skeletal muscles

3.) Budding neuromuscular junction and uptake into peripheral nerve ending, can also enter without muscle movement.

4.) Retrograde axonal transport

5.) Replication within ventral horn neurons and dorsal root ganglia

6.) infection of spinal neurons and axonal transport to brain

7.) infection to brain neurons

8.) Dissemination of virus to extra CNS sites (salivary glands)

Disease course for Rabies

1.) Incubation period: 2-3 months but can range from 1 week to several years

2.) Initial symptoms include fever pain tingling or burning sensations at the wound site

3.) Furious rabies causes hyperactivity and hydrophobia, leading to death within days while paralytic, accounting for 20% of cases cause slaw coma.

4.) Paralytic form is often misdiagnosed leading to underreporting

symptoms for rabies

delirium, agression, drooling, muscle spasms, dizziness, and Hallucinations.

Werewolf

what treatment is used after exposure to the victim from rabies?

Post-exporsure prophylaxis (administration of rabies immunoglobulin)

How long does an animal need to be kept in Quarantine after biting a person?

10 days

How long does an animal need to be kept in Quarantine after potentially being exposed to a rabid animal?

6 months

what family is the Ebola from

Filoviridae family

Bio safety levels

BSL-1: Suitable for work with well-characterized agents that do not cause disease in healthy humans, requiring basic safety practices and no special containment.

(BSL-2): Designed for work with agents that can cause mild to moderate disease, requiring additional precautions like protective clothing and limited access.

(BSL-3): Intended for work with pathogens that can cause serious or lethal disease through inhalation, requiring specialized ventilation and containment measures.

(BSL-4): Reserved for the most dangerous and exotic pathogens, posing a high risk of aerosol-transmitted infections, requiring complete isolation and the use of full-body suits with positive pressure.

Ebola is found in Fruit bats and also found in carcasses of chimps and gorillas and antelope

when was the first Ebola Outbreak and what are some facts

first found in 1976 in the DRC

318 cases with 218 deaths (88% death rate) one of most deadly in history.

Symptoms of Ebola appear 2-21 days after exposure to virus. average is 8-10 days. progress from dry to wet symptoms . advanced stages had multiple organ failure, internal and external bleeding, impaired kidney and liver function.

Clinical course of Ebola

1.) Exposure

2.) Incubation Period (8-10 days but range from 2-21 days)

3.) Symptoms begin (1-3 Weakness fever, and flu-like symptoms) (4-7: Vomiting diarrhea and hypotension) (7-10 days: Confusion possible bleeding typically minor shock)

4.) recovery or death

When was the worst Ebola outbreak known

2014-16 in Guinea which spread to 3 continents.

transmission of Ebola

blood, organs, bodily fluids, contaminated objects, infected animals, close contact, burial ceremonies, and transmission from hospital.

Notes:

From 1976-2020 over 28 outbreaks of ebola have occurred in Africa

Usually one to few hundred people infected, with exception of 2014-16, which had many many people infected and each outbreak had a death rate of 25-90%. Mostly from Zaire (DRC)

Why was Ebola 2014 larger outbreak than rest?

Rural, urban spread.

epidemic had 40% mortality but more spread of infection.

due to differences in virus strain or other factors.

What is special about the Ebola virus vaccine

they use another virus from livestock, and change its RNA polymerase in order for it to target the Ebola virus. the virus was called (vesicular Stomatitis Virus VSV) and it did not affect humans.

What percentage develop paralytic symptoms in rabies

20%

Where was the first anti-viral drug developed?

Zaire (DRC)