in this lesson: today is thursday, february 8th, 2018 · •lactobacillus acidophilus –found in...

Today is Thursday,February 8th, 2018

Pre-Class:

You’ve been on antibiotics, right?

Were they for a bacterial infection(s), viral infection(s), or both?

Oh, and get that POGIL thing…yeah.

In This Lesson:Microbiology

(Lesson 2 of 3)

Today’s Agenda

• Bacteria

• Viruses

• Where is this in my book?

– Chapters 19 and 27 (but we’ll do 27 first).

By the end of this lesson…

• You should be able to distinguish between bacteria and viruses on the basis of appearance, structure, reproduction, and classification.

• You should be able to identify types of vaccines and their mechanisms.

Let’s Begin at the Beginning [of Life]

• We’re going to start with bacteria.

– Hey look! There’s some right over there

• TED: Jessica Green and Karen Guillemin – You are Your Microbes

Bacterial Information Road Map

1. General information

2. Naming (shapes and growth patterns)

3. Cell wall details (gram-positive/negative)

4. Other structures

5. Reproduction and gene transfer

6. Resilience

7. Metabolism

8. Treatment

9. Impact

1. Six General Facts about Bacteria

1. They’re microscopic prokaryotes.2. They’re unicellular.3. They’re the most numerous organisms on Earth.4. They’re the oldest form of life on Earth.5. Bacterial infections are typically localized (occur

at only one point in the body).6. Antibiotics can be used as treatment for bacteria

so long as the bacteria are not resistant.

(P.S. Viruses don’t respond to antibiotics.)

Scale of the Universe

• For a relative size comparison, let’s use the scale of the universe.

• Scale of the Universe.lnk

Differences from Archaea

• True bacteria are about as distantly related from archaea as they are from eukaryotes.

• Some differences between them, other than millions upon millions of years of evolution:– How many subunits make up RNA polymerase

enzymes.

– How lipids link in their membranes.

– Pathogenicitiy (archaea aren’t pathogenic).

– Oxygen usage (archaea can’t have oxygen).

2. Bacterial NomenclatureRoot Words!

• Bacterial Shapes (sing./plur.)

– Coccus/cocci = sphere

– Bacillus/bacilli = rod

– Spiral/spirillum = spiral-shaped

– Vibrio = curved sides

• Bacterial Names (growth)

– Diplo- = pair

– Strepto- = chain

– Staphylo- = bunch

Bacillus (Plural: Bacilli)

http://commtechlab.msu.edu/sites/dlc-me/zoo/Pf07002.jpg

Coccus (Plural: Cocci)

http://www.yellowtang.org/images/1812.jpg

Spiral-Shaped or Curved

http://biology.touchspin.com/images/spirillum.jpg

Fun fact: Syphilis is caused by a spiral-shaped bacterium known as a spirochete.

It’s time to play…

• …IDENTIFY THAT BACTERIUM!

– To win each of the five rounds, you’ll need to correctly identify the shape of the bacterium on your whiteboard.

– Your team will receive 50 imaginary bonus points for correctly identifying the actual name of the bacterium.

• Some hints will be available.

• Some of them will also have growth pattern included in their names.

Round One

• Prefix:– Strepto-

• Shape:– Coccus

• Bacterium:– Streptococcus pyogenes– (strep throat)

https://s-media-cache-ak0.pinimg.com/736x/1f/db/ea/1fdbeaf5fde2f65d62be57a306767fd4.jpg

Round Two• Shape:

– Bacillus

• Bacterium:

– Escherichia coli

– Commonly known as E. coli

Round Three• Shape:

– Bacillus

• Bacterium:– Bacillus anthracis

• Produces anthrax.

– Can affect lungs, GI tract, or skin.

Anthrax

• Ever hear of those incidents in which prominent politicians/TV networks received anthrax in the mail in late 2001?

– [article]

Round Four

• Shape:

– Vibrio

• Bacterium:

– Vibrio cholerae

– Causes cholera

Round Five

• Shape:

– Bacillus

• Bacterium:

– Yersinia pestis

– Bubonic Plague

Some other name examples…• Staphylococcus aureus

– Staph infections.

• Enterococcus faecium– Found in intestines.

• Lactobacillus acidophilus– Found in yogurt.

http://www.bacteriainphotos.com/electron%20microscopy/Staphylococcus%20aureus%20electron%20microscopy.jpghttp://vivatfor.com/56-102-thickbox/lactobacillus-acidophilus-original-strain-317-402-narine.jpghttp://upload.wikimedia.org/wikipedia/commons/b/b4/Enterococcus_faecalis_SEM_01.png

3. Another way to classify bacteria…

• Bacteria can also be classified through the use of gram staining.

• Gram staining (named after Hans Christian Gram) is a technique by which a purple dye is placed onto bacteria.

• Bacteria with thick cell walls, often with large amounts of peptidoglycans (sugar/amino acid polymer) are considered gram-positive.

– They hold the purple stain (thus appear purple).

Positive and Negative

• Gram-positive bacteria have thick peptidoglycan(carb/protein) cell walls and are generally less toxic.

• Gram-negative bacteria have thinner cell walls with less peptidoglycan, but they have lipids mixed in.– These are called lipopolysaccharides (carb/lipid).

– They can’t hold the purple stain and appear pink.

– Additionally, gram-negative bacteria have a thin layer of cytoplasm in between layers of their cell wall.• Kinda like a yummy bacterial cytoplasmic sandwich.

• In short, gram-negative are generally more dangerous because it’s like they have two cell walls.

Gram-Negative v. Gram-Positive

http://www.microbiologybytes.com/introduction/graphics/Prokaryotes4.gif

Gram-Negative v. Gram-Positive

http://micro.digitalproteus.com/pics/grambacterium.jpg

Gram-Negative v. Gram-Positive

Gram-Negative[pink]

Gram-Positive[purple]

Antibiotic Resistance

• Often, the lipids (lipopolysaccharides) present in gram-negative bacteria are toxic and allow the barrier to be more resistant to drugs.

– Human cells don’t have much peptidoglycan, so antibiotics that attack peptidoglycan work well on gram-positive bacteria.

– Thus, antibiotics don’t work as well on gram-negative bacteria.

Examples

• Gram-positive Bacteria:– Streptococcus (strep throat)– Staphylococcus (staph infections)– Bacillus (anthrax and others)– Clostridium (botulism, gangrene, tetanus, colitis)– Listeria (meningitis)

• Gram-negative Bacteria:– Spirochetes (syphilis, lyme disease)– Neisseria (gonorrhea)– E. coli– Salmonella– Heliobacteria (ulcers)– Wolbachia (infects nematodes, insects, arthropods – leads to

heartworm complications in dogs).

http://www.hhmi.org/biointeractive/Antibiotics_Attack/frameset.html

4. Other Bacterial Structures

• Bacteria have:– Cell Wall– Cell Membrane– Flagella (sometimes)– Ribosomes– Genetic material in a single circular chromosome and in

small other loops called plasmids (in a nucleoid).• The nucleoid is the region of the cell where the DNA is found.

– A capsule – a sticky protein/sugar layer outside the cell wall.– Pili (singular: pilus) for attaching to one another.– Fimbriae (singular: fimbria) to attach to a substrate or one

another.http://micro.digitalproteus.com/pics/grambacterium.jpg

Bacterial Flagella

• Note that bacterial flagella are different between eukaryotes, bacteria, and archaea.– They’re analogous structures.

• Also, about half of all prokaryotes are capable of taxis.– Fun fact: Some bacteria can move 50 μm per minute, which

translates to 50x their cell length per minute.• Or a 5 ½ foot tall person running 190 miles per hour!

5. Bacterial Reproduction

• 36 hours of unchecked bacterial reproduction – starting from a single cell – can lead to enough bacteria to form a foot-deep layer across the entire Earth.

• Two days? They’d weigh more than Earth.

Bacterial Reproduction

• Most bacteria reproduce by binary fission:

– Copy the DNA ring, split in half.

• This is the only true way for bacteria to reproduce, but there is no sharing of genes.

– Thus, aside from mutations, there is a lack of diversity.

• To make up for that…

Bacterial “Reproduction”

• Some undergo conjugation:– Make a bridge between bacteria and

exchange DNA/genetic material.– They pull one another together using their

pili.• Fun fact: The ability to do this comes from a

gene found in the chromosome or plasmids known as F Factor (fertility factor).

• The idea that bacteria can trade genes between them without sexually reproducing is known as horizontal gene transfer.– This term applies to all organisms.– Horizontal gene transfer is not just a

bacterial thing, though it may be most common in them.

Sex Pilus

Bacterial “Reproduction”

• Recall from our DNA tech lesson that there are actually three ways for bacteria to introduce genetic variety:

– Transformation (last unit)

• Bacteria take up DNA in the environment.

– Conjugation (just now)

• DNA is transferred between two bacteria.

– Transduction (soon – sit tight)

• Viral infection by a bacteriophage virus.

6. Bacterial Resilience

• In unfavorable conditions, bacteria may create an endospore:– They copy their

chromosome and then surround it with a tough layer while the rest of the cell lyses (bursts).

– Bacteria can last several thousand years (or more?) like this, only to reactivate later.

http://student.ccbcmd.edu/courses/bio141/lecguide/unit1/prostruct/images/Bmeg_spore_01.jpg

A word about resilience…• On April 20th, 1967, the Surveyor 3 probe

sent by NASA landed on the moon.• In November of 1969, Pete Conrad from

Apollo 12 visits the probe on the Moon and retrieves the camera.

• NASA later finds that a colony of Streptococcus mitus [from Earth] survived in the vacuum of space in the lens without nutrients!

• As a result, NASA is now very careful to not contaminate other planets/moons with bacteria.– The Galileo space probe was deliberately

crashed into Jupiter to avoid accidentally landing on Europa, one of its moons, which is suspected to have water.

http://upload.wikimedia.org/wikipedia/commons/a/a7/Apollo12ConradSurveyor.jpghttp://upload.wikimedia.org/wikipedia/en/7/77/Surveyor_3_on_Moon.jpg

Not so fast!

• Turns out that further research concluded in 2011 uncovered that the camera was contaminated after it was opened after its return.

– Members of the camera team were wearing short-sleeved shirts and didn’t have proper-length scrubs.

• Still, it is a lesson in how easily contamination can occur, whether on launch or return.

• For more on resilience:

– There are diseases hidden in ice and they are waking up article

http://www.space.com/11536-moon-microbe-mystery-solved-apollo-12.html

7. Metabolism

• Bacteria utilize oxygen (or not) in a few different ways:– Obligate aerobes require oxygen to live.

– Obligate anaerobes cannot have oxygen to live.

– Facultative anaerobes can use oxygen to live but don’t need it.

• Separately, they may also form cooperative groups in…metabolic cooperation.

Metabolism

• Oxygen and cooperation aside, bacteria get their nutrients in three general ways:– Photoautotrophs use

photosynthesis.

– Chemoautotrophs use inorganic compounds made from sulfur, nitrogen, et cetera.

– Heterotrophs use dead animal/plant matter or are pathogenic.

http://academic.evergreen.edu/t/thuesene/Teach/SymbiosisWEB/WEBPAGE.html

8. Treatment

• The most common form of treatment for bacterial infection is the use of antibiotics.

• Antibiotics, like ampicillin (remember that?), interfere with bacteria’s various “cellular processes.”

• Using antibiotics improperly, however, can lead to the development of resistance.

– Remember that bacteria can transfer genes for resistance through plasmids.

http://www.webmd.com/food-recipes/news/20120106/antibiotics-food-animals-faq

About Resistance

• Take the bacteria called staph (short for staphylococcus).

• Staph is a common form of bacteria that does no harm as long as it is on the outside of the body or in the nasal passages.– About 1 in 4 people have it without knowing it.

• However, should it enter the body, it can cause a staph infection.– Symptoms include rash, chest pains, chills, muscle aches, or

more serious things like kidney failure.

• Thankfully, this infection can be treated with basic antibiotics like methicillin, penicillin, or amoxicillin.

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0004520/

But wait!

• About 1 in 50 people have a form of staph that does not respond to antibiotics. It’s resistant to them.

• These people actually have MRSA (pronounced “mersa”), which stands for methicillin-resistantstaphylococcus aureus.

• MRSA tends to pop up in hospitals, day care centers, schools, the military, or people that get tattoos.

• What’s more, MRSA is becoming harder and harder to treat as the bacteria evolve to become more and more resistant to antibiotics.– MRSA is getting WRSA.

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0004520/

Use of Antibiotics

• How does antibiotic use promote resistance?– Using antibiotics for viruses (viruses don’t respond

to them).

– Failure to take the full prescribed dose.• The most naturally resistant are the last to be around

and can then transfer resistance genes.

– Overuse of antibiotics.• For example, 80% of all antibiotics used in the United

States are given to…?

• Food animals! Many bacterial diseases in humans evolve resistance in food animals and “make the jump” to the human population.

Resistance Case-in-Point

• In 1929, Alexander Fleming discovered penicillin, an antibiotic created by Penicillium fungi.– It was actually a case of poor lab

technique – his Petri dishes growing staphylococcus bacteria were contaminated by the fungus.

• At the time it was a miracle drug and was widely effective.

• Today, it is widely ineffective.– Key: Antibiotics are growing more

expensive and are coming with more side effects.

http://www.lib.niu.edu/2001/iht9101395a.jpg

Alexander Fleming

Fleming’s Original Plate

Other Treatments

• Bacteria can often cause food spoilage.

• To combat bacterial action over the long term, preserved foods frequently use salt.– Ever notice canned and frozen foods are usually

very high in sodium?

• Salt creates a hypertonic environment and forces bacteria to lose water through osmosis (plasmolysis).

• Thankfully archaea are not generally toxic, because…

Extremophiles

• Archaea are often extremophilic and can survive salty environments.

• Case-in-point:– Below is Utah’s Great Salt Lake, which is 32% salt (!).– It appears pink because of archaea in the water.

• Little else can survive in that environment.

Archaea = Extremophiles

• Some example archaeaextremophiles:

– Methanogens make methane (and can’t take O2).

– Halophiles live in salty environments and use it to make ATP.

– Thermophiles can withstand temperatures above boiling in places like geysers and deep-sea vents.

9. Impact

• What role do bacteria take in our society?– More accurately, what role do we play in their society?

• Despite their bad reputation, 99%+ of bacteria are not harmful to humans and often help:– They decompose dead organisms.

– They convert atmospheric nitrogen to a usable form for plants.

Impact

• Helpful bacteria also:

– Are used in production of cheese and yogurt.

– Help in digestion.

– Produce vitamins (B12 and K in humans).

– Produce medicines (insulin – remember?).

– Make biodegradable plastics.

– Help purify water/clean oil spills.

Impact

• Of course, there are some bacteria (<1%) that areharmful and cause:– Plant diseases like blights and fruit rots.– Animal diseases like:

• Tooth decay.• Anthrax.• Plague.• Flesh-eating disease.• Sexually-transmitted diseases.• Cholera.• Tuberculosis.• Lyme disease.

• The general term for a disease causing biological agent is pathogen.

Bacterial Toxins

• Bacteria produce two general types of toxins:– Exotoxins are released by bacteria.

– Endotoxins are components of the cell membrane of gram-negative bacteria.• Remember I mentioned their membranes can be toxic?

– When the bacteria die and break down, endotoxins can be released.

Understanding Bacteria

• Cue the video!

Practice

• The Virtual Bacteria Identification Lab!

– (and Viral Epidemiology Activity)

So…bacteria.

• That’s bacteria.

• Single-celled survival machines that will be here long after we’re gone.

• Who else will be with them?

– Viruses.

• Let’s take a look at viruses for the second half of our lesson.

– Heads up: a virus particle is called a virion.

Viruses

• Pretend for a moment that you live in a time around the advent of microscopes.

• You’ve never looked through one before and have no idea that life can exist at a level you can’t see.

• If I were to tell you that something so tiny as to be invisible even to one of those microscopes could potentially kill you, you’d probably laugh at me.

– Enter viruses.

Virus Photo Gallery

• Ebola

Virus Photo Gallery

• Herpes

http://php.med.unsw.edu.au/embryology/images/d/d1/Herpes_virus.jpg

Virus Photo Gallery

• HIV

http://www.sciencedaily.com/images/2007/10/071020103343-large.jpg

Viruses

• Viruses are effectively just little bits of genetic material wrapped in a protein shell.

• Of course, they’re so much more than that.

• They’ve caused untold death, sickness, and misery, and yet they also hold incredible potential for good.

• How were they first discovered?

– In tobacco.

Tobacco Mosaic Virus

• In 1892, Dmitri Ivanowskypublished his findings on mosaic disease in tobacco plants.

• He concluded that an extremely tiny agent was responsible for the disease, which previously thought to be bacterial in nature.

– Actually, he assumed it was just a really tiny bacterium, but it turned out to be a virus.

http://www.apsnet.org/publications/apsnetfeatures/pages/tmv.aspx

Dmitri Ivanowsky

Virus Discovery

• In 1898, Martinus Beijerinckconfirmed Ivanowsky’s work.

• He reaffirmed that it was far smaller than a normal bacterium and is credited with naming it “virus.”

https://en.wikipedia.org/wiki/Martinus_Beijerinck#mediaviewer/File:Martinus_Willem_Beijerinck.png

Martinus Beijerinck

Scale of the Universe

• For a relative size comparison, let’s again use the scale of the universe.

• Scale of the Universe.lnk

Viruses

• Viruses can only be seen with an electron microscope:

Are viruses alive?• Viruses are not considered living things:

– They can’t produce waste or metabolize food.– They can’t grow.– They can’t reproduce without a host.– They don’t have cells.– They don’t respond to stimuli.

• That said, they have some characteristics of life:– They have genetic material.– They evolve.

Bacteriophage Hepatitis HIV

Evolution of Viruses

• Viruses appear to share a common ancestor with something called a transposon (or transposable element).

• Transposable elements (TEs) are sections of an organism’s genome that “jump” from one location to another.– Also called jumping genes.

• They were discovered in corn by Barbara McClintock.

http://www.stoccolmaaroma.it/wp-content/uploads/2013/12/barbara.gifBarbara McClintock

Parts of a Virus

1. Protein coat or sheath (known as a capsid).

1. Note: sometimes the capsid is surrounded by a membranous envelope made of a lipid bilayer.

2. Genetic Material (DNA OR RNA).

http://www.daviddarling.info/encyclopedia/V/virus.html

Viral Shapes

Rod-Shaped Polyhedral/Icosahedral Enveloped Complex

Viral Classification

• Viral classification can be really complicated.

• One of the most common methods is the Baltimore system, which is based on how viruses undergo transcription:

Baltimore Classification

I. Double-stranded DNA viruses– Herpes viruses and poxviruses

II. Single-stranded DNA viruses– Parvovirus

III. Double-stranded RNA viruses– Rotavirus

IV. Positive [5’ to 3’] single-stranded RNA viruses– Rhinovirus

V. Negative [3’ to 5’] single-stranded RNA viruses– Rabies, influenza

VI. Single-stranded RNA viruses with reverse transcriptase– HIV

VII. Double-stranded DNA viruses with reverse transcriptase– Hepatitis viruses (DNA to RNA to DNA)

Virus Families

Virus Infection/Reproduction

• There are two ways viruses infect and reproduce within a host cell:

– Lytic Cycle

• The quick and deadly one.

– Lysogenic Cycle

• The slow and secretive one.

• Used mainly by bacteriophages – more to come on that.

• Both serve to allow the virus to copy its genetic material, just like our cells do through DNA replication.

Lytic Cycle

Lytic Cycle

• During the lytic cycle, the virus injects its DNA into the host cell (or the virus is brought in entirely).

• The DNA is transcribed into RNA.

• The RNA is used by the ribosome to make new viruses.

• Cell eventually fills with viruses and bursts (lyses), releasing copies of the virus EVERYWHERE.

• Repeat.– Note: Viruses that only reproduce this way are called

virulent phages.

Lytic Cycle vs. Lysogenic Cycle

Lytic Cycle LysogenicCycle

Lysogenic Cycle

• Virus injects its DNA into the host cell (or the virus is brought in entirely).

• The viral DNA becomes part of the host cell’s original DNA and is called a prophage.

• The cell reproduces like normal and at first everything may be fine.

• Later on, a mutation or other factor may “turn on” the virus part of the cell’s DNA, starting the cell into something like the lytic cycle.– In other words, they can lay dormant for a long time, even after

the original infection.

• Phages that reproduce this way are called temperate phages.– That almost sounds nice.

Latency

• The lysogenic cycle provides us an opportunity to discuss another aspect of the infection process: latency.– Latency is the idea that an infection may lay

“dormant” in an organism.

• Often, a stressor prompts a latent infection to become active.

• This applies to bacterial infections as well as viral infections, although the lysogenic cycle is a classic form of latency.

Latency: Other Examples

• “Cold sores” are actually caused by herpes simplex virus and not the common cold.

– HSV type 1 mostly causes facial sores.

– HSV type 2 mostly causes genital sores.

– Outbreaks of herpes or recurrence of facial sores are due to stressors that put a strain on the immune system, allowing the herpes virus to get a little out of control.

http://www.nlm.nih.gov/medlineplus/herpessimplex.html

Latency: Other Examples

• Shingles

– Shingles is caused by the same virus that causes chickenpox – varicella-zoster.

• Having chickenpox leads to an integration of viral DNA with human cells.

• Stressors later in life can trigger a painful second outbreak known as shingles.

• Never had chickenpox? Not going to get shingles…

Latency: Mono

• “Mono” or infectious mononucleosis is transmitted by bodily fluids.– It’s the Epstein-Barr virus.

• The time from the initial infection to onset of symptoms –the latency period in which the virus is still contagious – may be weeks or months.

• Commonly known as “kissing disease,” the virus spreads through saliva very well (or blood/semen), even from shared drinking glasses or toothbrushes (gross).

– Fun fact: Mono can only be officially diagnosed by the presence of antibodies for the disease.• More next lesson…

http://www.cdc.gov/epstein-barr/about-ebv.html

Viruses in Animals

• Symptoms of a viral infection appear as a result of the virus:– Damaging or killing host cells.

– Causing infected cells to produce toxins.

• The damage caused by viruses may be temporary…– Like from the common cold.

• …or permanent.– Like from polio.

• Often, symptoms felt are your immune system responding to the infection.– You make the fever, in other words.

Viruses in Plants

• There are over 2000 known plant viruses which mostly contain RNA.

• They travel through the plant via plasmodesmata (junctions between cells).

Viruses in Bacteria

• Viruses are equal-opportunity, in that they also will infect bacteria.

• Because a virus is injecting its DNA into a bacterium, this represents the third way that bacteria can gain genetic variation.– Transformation

– Conjugation

– Transduction: infection of a bacterium by a virus, potentially introducing bacterial DNA from another cell.

• Video!– T4 Bacteriophage

Bacteriophages

• Bacteriophages also seem to look suspiciously like NASA’s lunar module:

http://www.theepochtimes.com/news_images/2005-5-30-phage.gif

http://starchild.gsfc.nasa.gov/Images/StarChild/space_level2/apollo11_lem_big.gif

Which prompts a comic:

http://pbfcomics.com/248/

Non-Viruses

• Viroids

– Viroids are pseudo-viruses that are known for infecting plants.

– They’re essentially circular RNA, much like plasmids, and they do not have protein coats.

– They’re the smallest known infectious agents.

Non-Viruses• Prions

– Most famously known as the cause of BSE (bovine spongiform encephalopathy – “mad cow disease”), prions (“pree-ons”) are misshapen proteins (no genetic material).

– They cause other proteins to also become misshapen, spreading like a virus.

http://msnbcmedia.msn.com/j/MSNBC/Components/Video/__NEW/tdy_1_rb_madcow_120425.grid-6x2.jpghttp://upload.wikimedia.org/wikipedia/commons/9/95/Aphis.usda.gov_BSE_3.jpg

Prions

• Prion-caused disorders include:

– Creutzfeldt-Jakob disease

• Can rarely occur spontaneously.

• Affects humans age 50-75.

• Causes dementia, muscle twitching, vision issues.

– Fatal Familial Insomnia

• Must be inherited.

• Strikes humans age 36-61.

• Sleep/wake cycle disruption causes coma, then death.

http://learn.genetics.utah.edu/content/basics/prions/

Prions

• Prion-caused disorders include:– Scrapie (goats and sheep)

– Bovine spongiform encephalopathy (cattle)

– Chronic wasting disease (deer and elk)

– Kuru (cannibals)

• Prions, since they’re not alive, cannot be killed, even with high temperature, alcohol, acid, or radiation.– A decades-old brain in a jar can transmit prions.

http://learn.genetics.utah.edu/content/basics/prions/images/BrainSections.jpg

And now…

• A look at some of the most well-known and/or destructive viruses out there…

– Note: You need not memorize all these details, however HIV comes with a few more terms with which you should become familiar.

HIV

• Retrovirus that leads to AIDS.– Uses RNA and reverse transcriptase.

• HIV “reprograms” cells that are part of the immune system and causes them to create more HIV viruses instead of the normal immune system cells.– Mainly, HIV attacks helper T cells. More to come next

lesson.

• The weakened immune system leads to AIDS.– HIV: Human Immunodeficiency Virus– AIDS: Acquired Immunodeficiency Syndrome

http://student.biology.arizona.edu/honors2000/group15/hiv_virus_info2.html

Wait, retrovirus?

• Retroviruses use RNA (instead of DNA) andreverse transcriptase (an enzyme).

– RNA is converted (reverse-transcribed) to DNA.

• The DNA can then be used to infect the host.

• Retroviruses often use the lysogenic cycle to reproduce.

• HIV is perhaps the most well-known retrovirus.

HIV

• Death from AIDS is caused by infection from some other pathogen because the body can’t fight back.

• Note: HIV mutates so frequently (about once per replication) that over one day an infected person can produce 1,000,000,000 different copies of the virus.

– Vaccines are thus difficult to develop.

Virus Transmission

• HIV has had several high-profile means of transmission. Here are two:

– Africa: AIDS Highway

– Worldwide: Patient Zero

• We’ve discussed Patient Zero before from a population evolution standpoint. Here, we look at it from a viral transmission standpoint.

HIV Transmission: AIDS Highway

• Technically called the Kinshasa Highway.

• Stretches across the DR of Congo and Uganda.

• The highway cut through sections of African rainforest that were very dense, previously isolating different populations.

• After opening up travel, prostitution became prevalent and truck drivers served as a frequent vector of disease from rest stop to rest stop.

http://student.biology.arizona.edu/honors2000/group15/hiv_virus_info2.html

Patient Zero

• When HIV became widespread and AIDS came to public attention in the 1980s, the CDC tracked the outbreak to a small group of homosexual men.– Note: HIV/AIDS likely originated early in the 20th century.

• One of these men was identified as a possible “center” of the network and was thus identified as Patient Zero.– Gaëtan Dugas, a flight attendant for Air Canada.

• It remains unclear whether Dugas, who died in 1984, was actually Patient Zero (he probably wasn’t), but it is clear that he continued to have unprotected sex despite knowing he had some form of contagious condition.

http://s12.bdbphotos.com/images/80x80/9/h/9hs68znwu0cb08bn.jpg

Patient Zero Disclaimer

• It’s important to note that Dugas was certainly not the first victim of AIDS.

• In fact, the first victim in the United States (confirmed) was Robert Rayford, who died at the age of 16 in 1969.– He lived outside St. Louis and had no blood transfusions.– How he contracted the disease is unclear.– Dugas, on the other hand, may not be Patient Zero according to

some researchers.

• Recent research suggests the transmission of HIV from primates to humans first occurred in the real Patient Zero in Kinshasa, Congo, in the 1920s.– Adding to the complication: HIV moved to humans 13 times but

the current pandemic is a result of only one of those transmissions.

Influenza• An outbreak of the Spanish flu led to a

pandemic in 1918. Also caused by the H1N1 flu virus, it lasted two and a half years, spreading from pole to pole and across the globe, killing between 50 and 100 million people and infecting around 500 million.– That’s like killing 3+% of the human

population and infecting 27+%.– More were killed than by the bubonic

plague (although the population was higher).

– The U.S. average life span was lowered by 10 years and over 800,000 died.

– In one four-week period in Philadelphia, 12,191 people died and 47,094 cases were reported.

• The pandemic seemed to end nearly as fast as it arrived.

http://www.upenn.edu/gazette/1198/lynch4.htmlhttp://4.bp.blogspot.com/-tQ08DTloWNA/TcH5ZbdjlzI/AAAAAAAAAHs/FPFkgpAZ67g/s1600/1918-flu-pandemic.jpghttp://blog.historians.org/images/406.jpg

Smallpox

• Spread most often by bedsheets, clothing, and droplets of saliva, the smallpox virus had two forms.– Variola Major: Could be deadly.– Variola Minor: Less likely to be deadly.

• Symptoms of both include fatigue, aches, rash, bleeding, and delirium.

• During the 1970s, the WHO (World Health Organization) wiped out smallpox, leaving the only known samples in:– CDC Headquarters, Atlanta, GA– State Research Center of Virology,

Koltsovo, Russia

http://img.medscape.com/

Smallpox

• [Not-so] fun fact:– Lord Jeffrey Amherst, commander of

British forces during the French-Indian War (1756-1763), considered using biological warfare in the form of sending smallpox-infected blankets to Native Americans.

– It’s unknown if it ever actually happened, but it was definitely at least discussed.

– Also, there just so happened to be an outbreak of smallpox in Native American populations shortly thereafter.

http://www.biographi.ca/bioimages/original.5460.jpghttp://www.straightdope.com/columns/read/1088/did-whites-ever-give-native-americans-blankets-infected-with-smallpox

Bastard Lord Jeffrey Amherst

Ebola Virus• Origin in Africa near the Ebola River,

Sudan, in 1976.– Symptoms include weakness, vomiting,

chills, headache, coma, disorientation…– …but typically NOT liquefaction.

• The Hot Zone and the Mythos of Ebola article

• Outbreaks in DR Congo, Uganda, Gabon, Zaire, Sudan, have killed hundreds since then.– Spare lab accidents have killed individuals

in Russia as well.

• Most recent outbreak to kill more than one person was in the 2014 epidemic.– 8800+ deaths.

• Near-outbreak in Reston, VA, in 1989.– Subject of The Hot Zone (and the movie

Outbreak, kinda).

http://upload.wikimedia.org/wikipedia/commons/a/ab/7042_lores-Ebola-Zaire-CDC_Photo.jpg

Ebola Case #3 – Nurse Mayinga

Baculovirus

• Baculovirus infects invertebrates, most notably caterpillars.

• An infected caterpillar is “reprogrammed” to climb to the top of a tree where it usually dies.

• The virus, having reproduced via the lytic cycle, then liquefies the caterpillar so that the next rain sends virus copies down throughout the leaves other caterpillars are eating, infecting them.– Not a virus: Snail Zombies video!

http://www.trevorwilliams.info/images/ODVs_in_OB.jpg

Rabies• Rabies is considered the most

lethal virus on the planet.– The mortality rate is effectively

100%. That’s higher than ebola.

• The rabies virus (Lyssavirus) contains RNA, which ultimately interferes with RNA used by neurons/brain cells.

• Late stages of the disease are characterized by mouth foaming.

http://osp.mans.edu.eg/elsawalhy/Inf-Dis/Rabies.htmhttp://2.bp.blogspot.com/_F_sB-JFHT2Q/SXrE1pwPcdI/AAAAAAAAANc/maZtjmlnylw/s400/rabies.jpg

http://hlazyl.com/Rabies.htmlhttp://www.virology.net/big_virology/Special/Rabies1/Virions.JPG

Just to lighten the mood…

Understanding Viruses

• Cue the video!

Emerging Viruses

• Viruses that first appear in a population, or that exhibit large changes in incidence or range, are known as emerging viruses.

• This can lead to a:– Epidemic – widespread disease outbreak.

– Pandemic – nationwide/worldwide disease outbreak.

• Influenza, ebola, and HIV have all been or are emerging viruses.

• Here are some other examples…– *Quick note: Endemic means “specific to,” as in, “orangutans

are endemic to Borneo and Sumatra” or “the disease is no longer endemic to the United States.”

2009: H1N1

• Unfairly called swine flu(pigs are a mixing vessel but are by no means the source of the virus), H1N1 was a pandemic.

• It spread to 207 countries (that’s most of them), infecting 600,000 people and killing 8000.

• Cue the stupid…

2012: Hantavirus• Hantavirus had a minor outbreak in Yosemite

National Park, leading to 10 cases.

• The virus is spread by rodent urine/droppings/saliva.

• Symptoms include fever, fatigue, and muscle aches, followed by coughing, shortness of breath, and fluid-filled lungs.

– Mortality rate = 38%.

2015: Measles

• Measles was eliminated from the United States in 2000.– Not from the world. Thus, travelers to the United States

represent, in a way, a measles vector, and the vast majority of cases have been imported from other countries.

• The incidence of measles has risen since 2000, with outbreaks in 2008 (91% unvaccinated), 2011 (89% unvaccinated), 2013 (82% unvaccinated), 2014 (unvaccinated Amish communities), and 2015 (82% unvaccinated).

• In 2015, 84(+?) people contracted measles from Disneyland in California.

http://www.cdc.gov/measles/cases-outbreaks.html

Measles

• Measles is caused by morbillivirus (AKA measles virus – MeV).

– Negative single-strand RNA virus – Class V.

• Symptoms of measles include rash, high fever, cough, runny nose, and watery eyes.

– However, it’s also the most deadly childhood disease.

http://www.cdc.gov/measles/cases-outbreaks.html http://phil.cdc.gov/phil/details.asp?pid=132

Measles Vaccine

http://www.historyofvaccines.org/content/timelines/measleshttp://www.cdc.gov/mmwr/preview/mmwrhtml/figures/r6204a1f1.gif

First Vaccine Licensed

Basic Reproduction Number: R0

• The basic reproduction number is given by R0 (“r-nought”) and indicates how many new cases of a certain disease can be generated by one case of a disease.– In other words, if I’m sick, how many of my students will

likely come down with my illness as a result of being around me before I get better?

• Let’s take a look at some R0 values for well-known diseases, courtesy the World Health Organization (WHO).– Side note: The R0 value for diseases spreading through

immunized (or partially immunized) populations is called RE (the effective reproduction number). It’s lower.

R0 ValuesDisease R0 Transmission Mode

Ebola (2014) 1.5-2.5 Body fluids

Influenza (Spanish Flu, 1918) 2-3 Aerosol/Airborne

SARS (respiratory disease from ‘02-’03) 2-5 Aerosol/Airborne

HIV 2-5 Sex

Mumps 4-7 Aerosol/Airborne

Rubella (German Measles) 5-7 Aerosol/Airborne

Polio 5-7 Fecal-oral

Smallpox 5-7 Aerosol/Airborne

Diphtheria 6-7 Saliva

Pertussis (Whooping Cough) 12-17 Aerosol/Airborne

Measles 12-18 Aerosol/Airborne

Video

• Vaccine-Preventable Disease Outbreaks Around the World

One more outbreak…

• Zika virus, 2016:– Spread by mosquito and leads to fever, rash, and joint pain.

– For pregnant women, zika can cause microcephaly in the fetus (a birth defect that leads to underdevelopment of the skull and brain).

– Vox – Zika Virus Explainedhttps://www.cdc.gov/zika/geo/active-countries.html#modalIdString_CDCImage_0

Virus Treatment

• We’ve been talking a bit about vaccination.

• Let’s explore that further, starting with one of the most unethical experiments ever performed (but let’s be thankful it was).

– P.S. Maybe now’s a good time to remind you that viruses do not respond to antibiotics.

– It’s like zombies. How do you kill that which is not alive?

– That said, there are antiviral drugs out there…

Vaccines

• In 1796, Edward Jenner injected an eight-year-old boy (James Phipps) with pus from cowpox.

• He then INJECTED THE SAME KID WITH SMALLPOX! and found that he was immune.

• He also injected several other children, including his own (at 11 months), and referred to the medicine as “vaccine” from vaccafor cow (Latin).

http://www.bbc.co.uk/history/historic_figures/jenner_edward.shtml

Edward Jenner

Vaccines

• For the record, people had been practicing “vaccination” in the most casual sense prior to Jenner’s experiment, but he was the first to formalize it in an experiment.

• Since Jenner, vaccines are similarly created by isolating the virus, sometimes from a single patient, and then developing a vaccine.– Case-in-point: The measles vaccine was developed

from a virus isolated in David Edmonston, a 13-year-old student in Boston, MA.

Types of Vaccines

• Similar Pathogen [Live]– Use a virus that’s close enough to the target virus.– Example: Cowpox used to vaccinate against smallpox.

• Live-Attenuated [Live]– Create a strain that is weakened by growing it in cells or

under conditions where it doesn’t thrive.• Eventually, mutations cause it to lose its potency.

– Example: Measles virus.

• Killed– Use heat, radiation, or chemicals to disable the virus.

• Killed vaccines don’t produce a full immune response and need boosters.

– Example: Polio virus.

Types of Vaccines

• Toxoid– Isolate the toxin produced by the pathogen and weaken it

chemically.• Often, an adjuvant (usually aluminum salts) is added to boost the

immune response.

– Example: Tetanus [bacterium]

• Subunit– Use a small part of the virus to create an immune response,

like maybe just a piece of the capsid.• Since it’s just a piece of the pathogen, there is no risk of infection.

– Example: Anthrax [US version – former USSR countries use an attenuated version]

Types of Vaccines

• Naked DNA

– Use PCR to generate many copies of a gene, then use restriction enzymes to transform a bacterial plasmid.

– The vector (transformed plasmid) is amplified further and introduced to the body.

• Not much of the vector actually gets into cells, but the ones that do (~1%) stimulate an immune response.

– Example: Experimental HIV vaccines.

Here’s this.

• I must acknowledge the anti-vaccination “debate.”

• Vaccines – An Unhealthy Skepticism

Some Other Things to Consider

• “If everyone is vaccinated, how can someone that is not vaccinated pose a threat?”– No vaccine is 100% effective.

– As an example, the MMR vaccine (measles, mumps, rubella) is 93% effective if you’ve had one dose; 97% effective if you’ve had two.• That’s if you’re even exposed to the virus.

– The CDC aims for a 90% vaccination rate.• While no single vaccination is 100% effective, if at least 90%

of a group is vaccinated, the risk of the disease even being present is vastly reduced, making the exposure rate go down and thus making the vaccine more effective.

http://www.cdc.gov/

Some Other Things to Consider

• “If I choose not to vaccinate, how is there a risk to anyone but me?”

– See previous slide.

– Oh, and remember that there are others that cannotbe vaccinated due to already compromised immune systems.

– A child with leukemia is unable to be vaccinated but is quite obviously still at risk for disease.

• That includes diseases that can be prevented by vaccinating everyone around that child.

http://www.cdc.gov/

Some Other Things to Consider

• “Aren’t there side effects?”

– Sure. Any medication has side effects.

– In the case of MMR again, the only side effects that were serious included fever and possible seizures, at a rate of 1 in 3000 patients.

– You know what else has bad side effects?

• Measles, mumps and rubella.

• For individuals under five years old, measles has a substantial risk of causing brain swelling and death.

http://www.cdc.gov/

Some Other Things to Consider

• “Can’t you pass a disease on even if you’re vaccinated?”

– It’s possible, but highly unlikely.

– Case-in-point: Measles. Measles is spread through moisture in the air, usually propelled by a cough from the infected person.

– If a droplet/sputum were to land on a vaccinated person, they would somehow need to pass that droplet on to someone else, who in turn would still only be 3-7% likely to catch it if they were vaccinated.

• Vaccinate enough people and the germ really has nowhere to go.

http://www.cdc.gov/

Some Other Things to Consider

• “What about the mercury?”– What about the chlorine in table salt?

– The mercury in vaccines (which has been removed in most of them anyway), was still not the same mercury compound that builds in seafood. In fact, you’re more likely to get mercury poisoning that way.• FYI, this is the compound known as thimerosol.

– The same goes for aluminum (more in baby formula than in vaccines).

http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/UCM096228

Some Other Things to Consider

• “In the past, didn’t people used to encourage chicken pox spreading among children? That’s clearly safe – why can’t we just do that?”– You could, but now you’re arguing to have the disease

instead of…what? The possibility you may have a side effect that’s showing up in a small fraction of patients? Does that make sense?

– By the way, having chickenpox as a child may prevent you from getting chickenpox again, but it guarantees you a risk of shingles when you get older.• So there’s that.

http://www.cdc.gov/

Some Other Things to Consider

• “I heard vaccines cause [insert disease here].”– “Hearing something” is known as an anecdote.

• Not to mention, correlation ≠ causality.

– As I said, there are side effects to vaccines, but nothing on the scale of what people are saying (and definitely not autism).• No peer-reviewed scientific paper has ever found a link to autism.

Ever.

• You need statistics and a large enough sample size.

– Not to mention, we don’t have polio or smallpox in this country because of vaccines, and that’s not just correlation.• Those vaccines prevented the deaths of millions and have never

been linked to other side effects. They were new once too.http://www.cdc.gov/

Some Other Things to Consider

• “Can’t I just quarantine myself if I become ill with [insert disease here], thus preventing its spread?”

– You could, but it’s unrealistic to think it would be as safe as vaccination. Here’s why:

• For the vast majority of diseases, it’s possible to spread the pathogen without having any symptoms. You’re a disease vector even before you know it.

• How likely is it you can really quarantine yourself? Could you cut yourself off from friends, family, work, school, grocery shopping, neighbors… the list goes on.

http://www.cdc.gov/

Anyway…

• Do you have questions?

• Disclaimer: Remember that I’m not a doctor, but I do have evidence.

Antiviral DrugsInfluenza

• Let’s use influenza as an example.

• There are relatively few anti-influenza drugs on the market right now.

• Two common ones include:– Tamiflu® (oseltamivir)

– Relenza® (zanamivir – inhaled)

• So how do they work?– In the case of the above drugs, they inhibit

neuraminidase.• Let’s talk about this one.

What’s the swine flu’s official name again?

• Swine flu is officially known as H1N1.– The H stands for hemagglutinin.

– The N stands for neuraminidase.

– The numbers are for variants on those molecules.

• Hemagglutinin is a glycoprotein helps the virus’s capsid attach to the polysaccharide chains on the outside of the cell membrane before injecting its genetic material.

• Neuraminidase is an enzyme that cuts the ends of the polysaccharide chains as the viruses exit the cell to avoid them getting stuck.

Antiviral DrugsInfluenza

• The drugs mentioned are neuraminidase inhibitors and serve to stop the virus from exiting cells.

– As you can guess, it doesn’t stop infection but significantly hinders its ability to spread.

• Drugs targeted at hemagglutinin attempt to prevent attachment of the virus to the cell.

– The body may also utilize antibodies (next lesson) to do the same thing.

For more on H and N…

• Technical:

– Influenza Virus Mechanism video

• Not-so-technical:

– NPR – Flu Attack – How A Virus Invades Your Body

Antiviral DrugsHIV

• AZT (azidothymidine, known commercially as Retrovir®) is an anti-retroviral drug targeted at HIV.

• Specifically, it’s a nucleoside reverse transcriptase inhibitor (NRTI).

• As the name suggests, NRTI drugs inhibit the ability of the virus to replicate by preventing it from reverse-transcribing RNA to DNA.

Viral Redemption?

• Viruses don’t really do much in the way of good for organisms.

– Either they don’t make them sick…or they do.

• However, their incredible ability to infect is starting to be turned around and viruses are being engineered as DNA delivery mechanisms.

– Doctors Using HIV to Treat Cancer video

Closure

• Giant Microbes!

• http://www.giantmicrobes.com

Closure

• Pandemic II