Bio 118 Umich Exam 2, Viruses, Measles, Bio 118 Measles, Syphilis, Bio 118 Columbian exchange, The Columbian Exchange, Bio 118 smallpox, Biology 118—Smallpox

Scientific name for syphilis bacterium

Treponema pallidum

mode of transmission of syphilis

-is an STD/STI

-Infection more general than disease.

-Can also be transmitted by blood contact

-Can also be transmitted by direct contact with open chancres

disease related to syphilis

Lyme Disease

disease syphilis evolved from

Yaws (south american form)

-DNA sequencing from ancient bones shows very little difference between the two

-not 100% proved

Year syphilis struck Europe

1493

Stages of Syhphilis

Primary -- mild and goes away

Secondary -- mild and goes away

Latent -- no symptoms, can last for many years

Tertiary -- destruction of tissues

does not go away

often does irreversible damage

Early treatments for syphilis

mercury rubs

malaria

First chemotherapy

-"Dr. Erlich's Magic Bullet"(Paul Erlich)

-Salvarsan (Arsphenamine), an arsenic compound 1910

modern syphilis treatment

single dose of penicillin for active, multiple doses for latent

"dirty disease"

syphilis as "dirty"

-prostitutes

-African Americans

-immigrants

many refused to treat syphilitics

Progressive movement

-social hygiene movement (WW1):

WCTU and the Catholic Church forbade discussion of condoms and even discouraged education about cures

Public health workers argued that sex education and condoms were necessary because moral education had failed

prophylaxis

-action taken to prevent disease, especially by specified means or against a specified disease:

-condoms, post-coital treatments with mercury

-90% effective

The Tuskeegee Study

The Tuskegee Study of Untreated Syphilis in the Negro Male, also known as the Tuskegee Syphilis Study or Tuskegee Syphilis Experiment was an infamous clinical study conducted between 1932 and 1972 by the U.S. Public Health Service

scientific name of smallpox bacterium

Variola major

(also V. minor or V. intermedius)

Smallpox + native americans

-One of the diseases that wipe out as much as 90% of the native populaton of North America

-First disease with vaccination

-First disease eradicated from the planet

pox

any rash with pimples (often becoming pustules)

cause of smallpox

-Caused by a virus

-Inhalation of droplets or dust from pustules

-Contact with contaminated bedding or clothing

-About 50% of susceptible family members became infected

-Contact with corpses too

-Infectious from just before rash until last scab drops off

Smallpox phases

-First 10-12 days: no symptoms, but virus is replicating in lymph nodes

-Day 12-14: fever, aches, malaise, begins to be contagious

-Day 15-30: progression from macules to papules to vesicles to pustules to scabs

-Day 31-32: convalescence (scars for life)

mortality rates for smallpox

-Hemorrhage (95% fatal)

-Confluent irruptions on skin: skin sloughs off, high mortality (about 60% fatal)

-About 30% mortality for naïve populations

-during pregnancy:

About 60-75% -spontaneous abortion

Live births 55% deaths in 1-2 weeks

Mothers 50% death from hemorrhage

origin of smallpox

-Probably from domestication of animals

-Probably not before 10,000 yrs BC

-Oldest documented cases 1000-1500 yrs BC Egyptian mummies

-Probably from Africa

Not established in Europe until after 100AD (Population too thin for maintenance)

Variola major

-The only smallpox known until late 1800's

-Large DNA virus

-Related to other poxviruses of animals

-Humans not generally infected by others

-CHICKENPOX NOT A POX VIRUS

Last cases of smallpox

-Last natural case in Somalia, Oct. 1977

-Last lab case in Birmingham UK Sep. 1978

Lab stocks of smallpox

-Scheduled for destruction on June 30, 1999 (international treaty)

-April 22, 1999: US announced that Soviet Union has weaponized version of smallpox stockpiled and refuses to destroy its stock

defenses against smallpox

-Quarantine (old practice)

-Variolation (inoculation)-use smallpox itself

-Vaccination

variolation (smallpox)

-Introduced into Europe and North America in 1721

-Battle between miasmatists and congationists

-variolation = inoculation

-Entry to blood and lymph slower and gives immune system more time

-lifetime immunity

vaccination of smallpox

-Edward Jenner noticed that milkmaids got cowpox from cow udders

-Milkmaids did not get smallpox

Tried "inoculation" with cowpox

It worked! - works because Vaccinia resembles Variola (fools immune system)

vaccinia

vaccinia disease is a disease and immune lasts only 5-10 years and vaccinia is contagious (a problem)

smallpox eradication

-US stopped vaccination in 1972 (North America was smallpox free (since 1949)

-By 1975, very few countries had smallpox

importance of smallpox today

-Germ warfare

-British sent blankets and handkerchiefs to Pontiac, chief of the Ottawa, as a gift.

germ warfare

-Japanese army (unit 731) experiments (Bubonic plague, tyhoid, cholera, anthrax, smallpox, etc.)

-Minimal prosecution after war

Americans and allies needed the expertise!

scientific name of measles virus

Morbillivirus

complications of measles

-Pneumonia

-Swelling of the brain: deafness,

intellectual disability, seizures

-Eye infections (blindness)

why is measles a "childhood disease"?

-Reproductive index (Ro), which Ro is about 15-20 (From a single person, 15-20 people can also get infected, then spread to 15-20 more each, etc.)

-if Ro less than 1, epidemic will die out. greater than 1, epidemic will continue

Origin of measles

-Rinderpest: highly contagious for ungulates (cattle, etc)-related cow disease

-Mortality approaching 100%

-Rinderpest epidemic by 10,000 yrs. Ago (same time as herding), animal to human transmission

-became human plague 1,000 to 1,500 years ago (needs large populations - enough newborns from survivors while virus still around)

Post-vaccine era of measles

-US: 50-500 cases a year

Usually from a single source (outbreak)

-Europe: about 10,000 cases a year

Often where vaccine can be avoided

-Japan: in 2000, there were 200,000 cases with 88 deaths (Vaccine problem)

Herd immunity

Maintenance of plague:

-How long are the infected still infectious

-How many people does an infected one contact

-What is the probability per contact that there will be a transmission

(herd immunity targets number 3)

reduce any of these, disease dies out

-if everyone else vaccinates, i wont have to

coverage limit of measles

-High Ro means high coverage required

-For measles, need at least 95% coverage to keep out of a population

MMR

-MMR = measles, mumps, and rubella

-vaccine

-Mumps = salivary glands swell, hurts to swallow, especially acidic things like OJ or pickles. As adult, it will often affect glands in groin

R0 for mumps and rubella = about 6 or 7

Wakefield

wrote fradulent paper about MMR vaccine and autism:

Certain kind of bowel disorder, claims was able to detect some of the MMR virus. people who had this "special colitis" were generally suffering from various levels of autism. No such thing as this kind of colitis; thought he saw something on X-Ray, but xrays were fake.

Richard Barr

lawyer that hired andrew wakefield to write paper on MMR

New World in 1940

-human settlement ca. 30,000 BC

-Isolation from Old World since about 10,000 years ago (was it really "new"?)

-General lack of large animals (died out in ice ages)

-All useful domesticatable animals died out between 40,000 and 10,000 years ago only LLAMAS remained

-Ice age accounts for lots of extinction, but not all—therefore, it is also due to hunting AND ice age

Transatlantic crossing of smallpox

-Many diseases didn't exist in north america until people brought them from other countries

-Took 2 cycles of smallpox to get across atlantic, so people died on the way

Santo Domingo

-smallpox reached Santo Domingo by 1519

-about 1/3 to 1/2 of the native population died (no spaniards died)

-then on to Puerto Rico, Antilles, and Mexico

Cortez

-Defeats a greatly weakened Aztec army

-Smallpox breaks out in the Aztec camp (not the Spanish) and decimates the army

-Cortez kidnaps Montezuma - killed

Crisis of Incan Succession

-great Incan emperor dies of smallpox and many others in royal family and in bureaucracy

-Nobles risk everything and find another candidate who dies of smallpox before crowned

-Two other sons began a great civil war of succession that divided the empire

Conquest of Incas

-Pedro Pizzaro arrived after the civil war weakened the empire

-came the Spaniards: horses, steel swords, guns, and immunity to Smallpox => No choice but to surrender

Verrazzano

-Verrazzano = puerto rican explorer

-1532 Sailed North from NC to RI

-By 1600, a lively British trade

-Trade = between british and north america

Smallpox epidemics

-A plague broke out (hepatitis A?) that raged for 3 years and probably killed 90% of the population of Northern New England!

-A smallpox epidemic in 1637 decimated Southern New England

DeSoto

-desoto = explorer

-led expedition from 1640-43 in searh of gold and fountain of youth

-Marched through Fl, GA, NC, SC, TN, AL, MS, AK, TX, and LA.

-He was a slaver

-Died along the way, but left a trail of disease and death behind.

-along mississippi: almost deserted in 1680s, Probable cause = disease carried by spanish pigs

Syphilis + Columbian Exchange

-First appear in Europe ca. 1493

-historians suggest syphilis couldve been part of the exchange

-Most likely derived from a South American form of Yaws

Syphilis Epidemiology

-Slow spread from 1493

-In 1494-5 Charles VIII of France invaded Italy and France

-India by 1498

Changing of Syphilis

-1494-1516: first small genital ulcers, then bad rash, then spread through body especially mouth, then deterioration and death

-Early days, syphilis was a rapidly moving disease

-1516-1526z: bone inflammation and degeneration, sometimes hard genital warts or corns

-1526-1540: general decrease in symptoms and sequellae

-1540-1560: decrease in the more spectacular symptoms, Gonorrhea symptoms become dominant

-1560-1610

continued decline in symptoms, add "noise in the ears" *this is the modern form we know today*

Treatment for Syphilis

-Old treatment: mercury, gaiacum wood

Malthusian Deadlock

-You will keep having kids until people are starving(Malthusian Deadlock), then you have to grow more food/expand (to break deadlock)

Potatoes vs Maize

-Potatoes: Milk plus potatoes is balanced nutrition, And the only foodstuff for most of the Irish population in the early 1800s, domestication easy

-Maize (like wheat): Deficient in several amino acids, Needs supplementation with beans or meat, maize domestication impossible

Columbian Exchange

-coined to describe the transfer of things found only on one side of the Atlantic to the other

-began with the voyages of Columbus in 1492

-continues to this day

-epidemic of diseases like smallpox and measles from europe led to death of about 90% of pre-Columbian population (native americans)

-led to massive pop decrease in Americas, but massive increase in Europe

Lack of large animals in Americas

-used to have horses, camels, mammoths

-sometime between 40,000-10,000 years ago most became extinct

-corresponds to approx time humans entered Americas

-climate change, killing

Smallpox at time of Columbus

-smallpox was endemic during this time in most of Europe

-death rate was 3-10%

-death rate in naive pops was 30%

Bones + syphilis

Diseases caused by T. pallidum exhibit pitted regions or large lesions in the bones of skeletons, especially on skull

-hard to distinguish yaws lesions from syphilis lesions

Conquest of Mexico and the Aztecs

-Mexico and Cortes joined to attack Aztec empire

-kidnapped king, who was killed eventually in a standoff

-Aztecs drove Spaniards out

-while Cortes looked for more soldiers, smallpox spread

-killed 1/3 of the pop

-battle left Aztecs in ruins

-conquered land became New Spain

-overview: smallpox came with Spaniards and enabled victory in Mexico

Conquest of Peru and the Inca

-before Pizarro left Mexico (starting point), smallpox had already reached Incan homeland

-death toll = catastrophe for Incas

-Spaniards easily defeated empire

-*smallpox was spreading in New World without European presence*

characteristics of viruses

-Obligatory intracellular parasites

-Contain DNA or RNA

-Contain a protein coat

-Some are enclosed by an envelope

-Some viruses have spikes

-Most viruses infect only specific types of cells in one host

antigenic

recognizable by immune response

viral genes

-Can be DNA or RNA

-Can be single or double stranded

-Can be linear or circular

viral receptors

-Usually proteins or parts of proteins on the outside of the virus (capsid or envelope)

-Fit some cellular surface molecule like a lock and key

-Interaction triggers a cellular response

life cycle of a virus

-Entry into a host cell

-Production of new viral genetic material

-Production of new viral genetic proteins

-Assembly of new virus particles

-Exit from the infected host cell

DNA vs RNA

-DNA = Library copy. Book of instructions. Stored and carefully edited

-RNA = messenger (tells the builders what to do)

retrovirus

any of a group of RNA viruses that insert a DNA copy of their genome into the host cell in order to replicate, e.g., HIV.

entry for viruses without envelopes

-first must attach using receptors (specific)

-if a match, then engulfment -- looks like phagocytosis

-capsid then in the cytoplasm but within a vacuole

-virus must uncoat without the genes being degraded

entry for viruses with envelopes

-first must attach to cell membrane using receptors -- quite specific

-if a match, then fusion -- like two soap bubbles

-that leaves the capsid free in the cytoplasm

how we fight viruses

-immune system is our best defense

(Vaccines can "prime" it)

-drugs are rare because "viruses are us"(most drugs that kill viruses, kill us too (remember that they use our machinery), even those that are "specific" for viruses can have side effects.)

best evasive actions for a virus

-Stop viral replication: hide genome in host genome but don't make anything; no antigens, no immune response

-Get from cell to cell quickly

as soon as "free" virus around, immune response will see it an begin to clear it

-for HIV, kill the immune response

viral disease examples

-Flu

-Smallpox and measles

-HIV

-Colds (hundreds of different viruses)

-Herpes (chickenpox, cold sores, genital herpes)

-Hepatitis

viruses vs bacteria

-bacterial are complete organisms

-bacterial evolution was separate from animals (so many functions are different, making them targets for drug therapy)

-bacteria are bigger

the smallest bacteria are about the size of the largest viruses

origin of viruses

*unsure*

-Escaped-genes hypothesis: clusters of genes physically escaped from bacterial or eukaryotic chromosomes long ago

Degeneration Hypothesis: organisms slowly lost genes required to make nucleic acids and proteins

Intracellular communication

Communication within one cell

Parasite

lives at expense of something else

General characteristics of viruses

-Contain DNA or RNA

-Contain protein coat

-Some enclosed in envelope

-Some have spikes

-Most only infect certain types of cells in host

Host Range

determined by specific host attachment sites and cellular factors

In the human body, nearly every system, tissue, and cell can be infected by one or more kinds of viruses. (True/False)

True

Viruses are large compared to eukaryotic and bacterial cells (true/false)

false (they are much smaller)

Capsid shape

usually icosahedral symmetry or helical tube

"bullet"

"cone"

antigenic

recognizable by immune response

Capsids characteristics

-proteins on outer surface can interact with host cell surface proteins

-often many copies of one or a small number of different proteins

Envelopes

-surround the capsid

-richly studded with proteins (antigenic, interact w host cell surface proteins)

-fuse with cell membrane during infection

What are envelopes made of

membrane lipids (fats)

Viral genes

-Can be DNA or RNA

-Can be single or double stranded

-Can be linear or circular

-Genome=thousands of nucleotides long (millions for bacteria, billions for eukaryotes)

Where are viral receptors

usually proteins or parts of proteins on the outside of the virus or envelope

How do viral receptors work?

Fit some cellular surface molecule like a lock and key, which triggers cellular response (engulfment/fusion)

Give virus primary host range

Life Cycle of Virus

1. Entry into host cell

2. Produce new viral genetic material

3. Produce new viral genetic proteins

4. Exit from the infected host cell

DNA

Library copy. Book of instructions. Stored and carefully edited

RNA

Messenger

ssRNA=one messenger

dsRNA=two messengers

Always like playing "telephone"

Retrovirus example

HIV

Retrovirus Entry (non-enveloped)

-Must attach using receptors

-if a match, then engulfment -- looks like phagocytosis

-capsid then in the cytoplasm but within a vacuole

-virus must uncoat without the genes being degraded

Entry (enveloped)

-First must attach to cell membrane using receptors -- quite specific

-If a match, then fusion -- like two soap bubbles

-That leaves the capsid free in the cytoplasm

RV Production of new viral genetic material

-Can be in nucleus or cytoplasm (depends on type of viral genetic material)

-Some do direct copies of DNA --> or RNA -->DNA conversation

-Others use "reverse transcriptase" to do RNA--> DNA convo

RV production of viral proteins

-Occurs in host cytoplasm

-Uses host machinery

RV Assembly of new virus particles--capsid

-proteins made in cytoplasm

-DNA/RNA get from nucleus to empty capsid

-capsid fills

-final modification to capsid (block DNA entry/mature outer proteins)

RV Assembly of new virus particles--attaching envelope

-capsid to inner surface of membrane

-viral protein accumulate in cell membrane

-bleb forms and surrounds virus

-eventually bleb contains capsid and breaks off as vesicle

-opposite of engulfment

RV exit from host cell

-enveloped viruses keep blebbing

-non-en less understood