Download Lecture 13 Virus and Simple Cells

Lecture 11:
STD’s and Viruses in Cells
Basic Structural Organization
• Membrane
• Cytoplasm
• Nucleus
Cell Membrane
Fluid Mosaic Model
-Fluid- kind of like a bubble
-Mosaic- Full of “Stuff”
1. Phospholipids (of course)
2. Protein (Oh no not again!)
3. Sterols- Structurally Important
-Not long chains
-Add flexibility to membrane
Receptors and Recognition
Receptors are sensors on the cell
-Nutrient levels
-Status of surrounding cells
-Divide or Die
-Activate or Suppress
Recognition
-ID tags
-Immune surveillance
Cell Membrane
Key Concepts
The membrane is an organelle
The membrane is dynamic
Membranes play a key role in cell function
• More than just a filmy covering
• Not just on the outside
Inside the Cell
More Membranes!
Organelles
Few Empty Spaces
Cytoplasm is the Desert in the Cell
Endomembrane System
1. Nuclear Membrane
2. Endoplasmic Reticulum (ER)
Rough ER
Smooth ER
3. The Golgi Body
4. Vessicles
5. Sarcoplasmic Reticulum
Endomembrane System
Nuclear Membrane
– Inner nuclear membrane
– Outter nuclear membrane
• Continuous with ER
• Nuclear Membrane Proteins
– Nuclear Lamina- Inner membrane
• Structure
• Role in Division
– Nuclear pores- Transport
Nuclear Pore Function
Endomembrane System
Endoplasmic Reticulum
• Site of Protein Synthesis
– Ribosomes- attached vs. “free”
– Protein tags for trafficking:
• Outside, Inside or in the Middle
• Inside the ER
– Post-Transcriptional Modification
• Glycosylation- sugar additions
• Glycosylation labels proteins for transport
– Transport
• New proteins shuttled to Golgi or Vessicles
Endomembrane System
Golgi Apparatus
• More post-transcriptional
modification
• Sorting and transport
– Default transport and Direction
• If in doubt secrete it
• Carbohydrate Synthesis
– Polysaccharides
• Pectin and hemicellulose
• Glycosaminoglycans
Endomembrane System
Vessicles
Secretory Vessicles
-Fuse with membrane and dump
contents
Lysosome and Peroxisome
-Degrade and recycle
Vacuoles
-Storage containers
Protein Traffic
• Protein made in the ER is folded
• Bits of the ER are transported to
theER
Golgi
Golgi and sorts
• The Golgi labels
proteins
• Bits of the Golgi are transported
to “vessicles”
– Secretory vessicles
– Lysosome
Recognizing
cells with viral
infections
Recognition
Endomembrane System
What Happens in Each Compartment
1. ER
2. Golgi
3. Vessicles
– Follow the protein
Basic Structural Organization
• Membrane
• Cytoplasm
• Nucleus
Membrane-bound Organelles
Nucleus
Mitochondria
Chloroplast
Sexually Transmitted Disease
Chlamydia
Gonorrhea
Syphillis
Trichomonas
Genital Warts
Herpes Virus
HIV/AIDS
Chlamydia
Cause
Intracellular bacteria
Symptoms (M):
Urethritis, epididymitis,
prostitis (mild to severe
burning)
Symptoms (F):
Urethritis, cervicitis
and PID.
Key features
Important cause of
infertility
No external sores
Asymptomatic:
Up to 20%
Incubation:
1-3 weeks
Treatment:
Antibiotics
Chlamydia
•Most prevalent of all
STDs
•Infection can facilitate
the transmission of HIV
infection
•A major cause of
infertility, ectopic
pregnancy, and chronic
pelvic pain
•pregnant women
infected with chlamydia
pass infection to infants
during delivery, results
in neonatal ophthalmia
(eyes) and pneumonia
(lungs)
CDC STD survalience 2002 http://www.cdc.gov/std/stats/chlamydia.htm
Gonorrhea
Cause
Intracellular bacteria
Symptoms (M):
Urethritis (mild to severe
burning)
Symptoms (F):
Urethritis, cervicidis and
PID.
Symptoms (M/F):
30-50% rectal infection
Pharyngitis, isolated from
pharynx (throat)
Important cause of infertility
Key features
Scaring in falopian tubes
increases chance of ectopic
pregnancy
No external sores
Asymptomatic:
Up to 20%
Incubation:
3 days to 3 weeks
Treatment:
Antibiotics
Increasing incidence of
bacterial resistance to
effective antibiotics
Gonorrhea
•Major cause of pelvic
inflammatory disease
(PID) in the US
•PID leads to serious
outcomes:
•tubal infertility
•ectopic pregnancy
•chronic pelvic pain
•Strong evidence that
gonococcal infections
facilitate the
transmission of HIV
infection
CDC STD survalience 2002 http://www.cdc.gov/std/stats/chlamydia.htm
Syphilis
Cause:
Key Features
Bacteria, spirochete
Symptoms (M/F)
Primary: Chancre (painless)
Secondary: Headache, fever,
sore throat, rash- trunk to
palms and soles.
Tertiary: Nervous system and
cardiovascular damage.
Leads to: meningitis,
dementia, neuropathy and
heart attack
Incubation: 21 days
Primary symptoms: 3-6
weeks,
Secondary symptoms: for
3-6 weeks, 3-6 weeks
after primary,
spontaneously resolve
Tertiary symptoms: years
after infection
Treatment: most
successful in first and
secondary stages
Trichomonas
Cause:
Flagellated protozoan
Symptoms (M):
Asymptomatic,
sporadic urethritis
Symptoms (F):
Vaginosis with
discharge (frothy
green) and
abdominal pain
Key Features:
Non-bacterial
parasite
Incubation:
3 to 28 days
Trichomonas
•Trichomoniasis is one
of the most common
sexually transmitted
diseases
•Mainly affects 16-to-35year old women.
•In the United States, it
is estimated that 2
million women become
infected each year.
http://www.cdc.gov/ncidod/dpd/parasites/trichomonas/factsht_trichomonas.htm
Genital Warts
Cause:
Human papilloma virus
(HPV =DNA virus)
Symptoms (M/F)
Painless
Coalesced condylomate
may cause discomfort
from size and location
A appear as flat,
smooth, small bumps,
or quite large, pink,
cauliflower-like lumps.
Key Features
Correlated with cancer
Treatment:
Cryotherapy
Difficult to distinguished
Asymtomatic (F) detection
with PAP smear
Asymtomatic (M) no HPV
test for men
Genital Warts
HPV infects the
genital area and is
spread through
genital contact.
Most HPV infections
have no signs or
symptoms;
therefore, most
infected persons are
unaware they are
infected, yet they
can transmit the
virus to a sex
partner
Initial visits to physicians’ offices:
United States, 1966–2002
Herpes Virus
Cause
Key Features
Herpes Virus (DNA virus)
Lifelong recurrent episodes
of painful genital lesions,
4 or 5 each year
Increased likelihood of HIV
transmission and
acquisition
Women who acquire genital
herpes in pregnancy:
potentially fatal neonatal
infection
Symptoms (M/F)
Fever, headache,
retention, swollen
lymphnodes. Genital
sores
Incubation: 8 to 16 days
Herpes Virus
Herpes simplex I and II: Cold sores vs. STDs
Herpes can make people more susceptible to
HIV infection, and it can make HIV-infected
individuals more infectious.
There is no treatment
that can cure herpes
Epidemic?
– Nationwide,
one out of five
– Between the late
1970s and the early
1990s, increased
by 30%
Herpes simplex virus type 2 infections — Percent seroprevalence according to age in NHANES II (1976-1980) and NHANES III (1988-1994)
AIDS (Acquired Immune
Deficiency Syndrome)
- Cause: Human Immunodeficiency Virus (HIV)
-Symptoms: fever, weakness, multiple infections, cancer
-Reported AIDS cases in Michigan: 13,500
An estimated 850,000 people in the US have HIV
Approximately 40,000 new HIV infections occur every year
One-third of infected Americans have not been tested and
are unaware of their status.
1 in 100 college students has HIV
The AIDS epidemic is shifting toward women. Women account
for 28 percent of HIV cases reported since 1981, they
accounted for 32 percent of those reported between July 1999
and June 2000
Human Immunodeficiency
Virus (HIV)
Cause:
Key Features
Retro virus (RNA virus)
• Virus that causes
Acquired Immune
Difency Syndrome
(AIDS)
No cure
No Immune system
Sexually transmitted
Blood transmission
Needles, and
transfusions
Adults and children living
with HIV/AIDS as of end 2003
Western Europe
North America
790 000 – 1.2
million
Caribbean
350 000 – 590
000
Latin America
1.3 – 1.9
million
520 000 – 680
000
North Africa &
Middle East
470 000 – 730
000
Eastern
Europe
& Central Asia
1.2 – 1.8
million
East Asia & Pacific
700 000 – 1.3
South
million
& South-East
Asia
4.6 – 8.2
million
Sub-Saharan
Africa
25.0 – 28.2
million
Australia
& New Zealand
12 000 – 18
000
Total: 34 – 46 million
Estimated adult and child deaths
from HIV/AIDS during 2003
Eastern Europe
& Central Asia
North America
Western Europe
12 000 – 18 000
Caribbean
23 000 – 37 000
2 600 – 3 400
North Africa & Middle East
30 000 – 50 000
35 000 – 50 000
Sub-Saharan Africa
Latin America
49 000 – 70 000
2.2 – 2.4
million
East Asia & Pacific
32 000 – 58 000
South
& South-East Asia
330 000 – 590 000
Australia
& New Zealand
<100
Total: 2.5 – 3.5 million
Estimated number of children
(<15 years) newly infected with HIV during 2003
North America
< 500
Caribbean
5 000 – 9 000
Western Europe
< 500
Eastern Europe &
Central Asia
800 – 1 200
East Asia & Pacific
North Africa
& Middle East
2 500 – 5 000
8 000 – 12 000
Sub-Saharan Africa
32 000 – 58 000
580 000 – 660 000
Latin America
8 000 – 12 000
South
& South-East Asia
Australia
& New Zealand
< 100
Total: 590 000 – 810 000
About 14 000 new HIV infections
a day in 2003
• More than 95% are in low and middle
income countries
• Almost 2000 are in children under 15 years
of age
• About 12 000 are in persons aged 15 to 49
years, of whom:
— almost 50% are women
— about 50% are 15–24 year olds
Global summary of the HIV/AIDS epidemic,
December 2003
Number of people
Total
40 million (34 – 46 million)
living with HIV/AIDS
Adults
37 million (31 – 43 million)
Children under 15
2.5 million (2.1 – 2.9 million)
People newly infected
Total
5 million (4.2 – 5.8 million)
with HIV in 2003
Adults
4.2 million (3.6 – 4.8 million)
Children under 15
700 000 (590 000 – 810 000)
Total
3 million (2.5 – 3.5 million)
Adults
2.5 million (2.1 – 2.9 million)
Children under 15
500 000 (420 000 – 580 000)
AIDS deaths in 2003
The ranges around the estimates in this table define the boundaries within which the actual numbers lie, based on the best available
information. These ranges are more precise than those of previous years, and work is under way to increase even further the precision of the
estimates that will be published mid-2004.
Occurrence of AIDS
among different races
Global HIV Epidemic
Lifetime Risk of AIDS Death for 15-year-old Boys, Selected Countries
Life expectancy in African
countries with high rates of HIV
20 year decrease in 10 years
What we’ve learned about therapy
Bad News
• Can’t Cure HIV
• Viral replication even with NO Detectable
Virus (<20 c/ml)
• Long term toxicity and intolerance
• Virologic failure leads to resistance
– Variables: Time, Load, Agent
• Resistant strains are transmitted
• Adherence (>80-95%) critical for virologic
suppression
• Good care requires experts
HIV = Death
Where does this leave a virus?
• Not able to replicate alone
• Not able to metabolize alone
• Not a life form
Vi´rus
Noun, virus - (virology) ultramicroscopic
infectious agent that replicates itself only
within cells of living hosts; many are
pathogenic; a piece of nucleic acid (DNA
or RNA) wrapped in a thin coat of protein
Classification
Eukaryotes
The Kingdoms
• Anamalia- Multicellular, consumers
• Plantae- Multicellular, consumers
• Fungi- Mostly decomposers
• Protista- One-celled, producers and
consumers
• Eubacteria- Normal bacteria
• Archaebacteria- Extreme bacteria
Prokaryotes
Virus Structure
Understanding a Virus
Components
Nucleic acid
Proteins
Life Cycle
Host Range
Types of Virus
HIV
Herpes Simplex
Baculovirus
Virus
General Description
1. Non-cellular infectious
agent
2. Protein coat wrapped
around nucleic acids
3. Cell dependent
replication
General Features
• Genetic material
– RNA or DNA
• Viral envelope
– Viral coat protein
– Glycoproteins
– Plasma membrane
from previous host
• Specialized Proteins
Virus Structure
Retrovirus
DNA Virus
Contains DNA or RNA but not both
Host Range
and Types of
viruses
Wide range
of hosts
Host Range
Bacterial Virus Model
•
1917, Discovery of
Bacteriophage
–
–
•
Why doesn’t everyone die
of bacterial dysentary?
What’s eating the bacteria?
The MSU story
–
–
1950, Harold Sadoff U of Ill:
Micro aerosols
1952, Hershey and Chase
Experiment
Bacteriophage
The Hershey and Chase Experiment
1.
2.
3.
4.
5.
Label protein or
DNA with radio
isotopes
Infect bacteria
with phage
particles
Sheer off the
phage (blender)
Separate bacteria
and phage
protein
Progeny of the
phage
The Hershey and Chase
Experiment
Bacteriophage
DNA is the infective material not protein
Bacteriophage are an example of a DNA
virus
DNA Virus Life Cycle
1. Attach and
Enter
2. Integration
3. Transcription
and
Translation
4. Assembly
5. Release
Baculovirus
Double-strand DNA
Virus
Two Morphologies
1. Polyhedryl
inclusion bodiesinsect to insect
2. Single viron
derived from
plasma membrane
of host
Very important tool
for molecular biology
DNA Virus Life Cycle
1. Attach and Enter
2. Integration
3. Transcription and
Translation
4. Assembly
5. Release
Retrovirus Life Cycle
1.
2.
3.
4.
Attach and Enter
Reverse Transcription
Integration
Transcription and
Translation
5. Assembly
6. Release
Retrovirus Life Cycle
1.Attach and Enter
2.Reverse Transcription
3.Integration
4.Transcription and Translation
5.Assembly
6.Release
Retrovirus Life Cycle
1.Attach and Enter
2.Reverse Transcription
3.Integration
4.Transcription and Translation
5.Assembly
6.Release
Retrovirus Life Cycle
1.Attach and Enter
2.Reverse Transcription
3.Integration
4.Transcription and Translation
5.Assembly
6.Release
STRUCTURE OF HIV
lipid
envelope
(proteins
span it, line
its inner
surface,
spike out
above it)
viral genes are integrated
into the host DNA
strands of
viral RNA
(two)
a strand of
viral RNA
undergoes
reverse
transcription
viral coat
(proteins)
intergrase
1.
2.
3.
4.
5.
6.
DNA is transcribed
viral RNA
enters cell
reverse
transcriptase
Attach and Enter
Retro transcription
Integration
Transcription and Translation
Assembly
Release
viral DNA
host cell
viral RNA
viral
proteins
budding
HIV Picture
HIV Transmission
How HIV causes AIDS
The Immune System
Programmed Cell Death
Proteins in HIV