Viruses and Prions
What is a Virus?
Outline of Lecture
• Viral basics and interesting facts
• Three interactions with host
• Influenza, herpes, genital warts
• HIV-AIDS
• Prions
• Discussion question--can viruses be beneficial?
Questions welcome anytime!
1. Viruses are obligate intracellular,
molecular parasites
2. Very small and infectious
3. The virus genome--either of DNA or RNA
4. Viral genome directs the production of
new virus particles
Fig. 13.2.
Figure 13.3
Fig. 13.03
A. Naked virus
B. Enveloped virus. Many
animal viruses….
Spike proteins are also
often “attachment
proteins” that attach to
specific sites host cell.
Envelope derived from host
plasma membrane…
Specialized
Transduction
Vaccinia Virus
Edward Jenner
First vaccine
Result = horizontal gene transfer
Fig. 13.11
Different Interactions with Host
Influenza
(pp. 586-588)
> Highly mutable virus - changes antigens very
quickly
Fig. 13.4
(modified)
> Many animal reservoirs
1.
Host cell
bursts
2. Host cell
survives, genome
modified,
Viral leakage
3. Host cell survives
genome modified,
new host
characteristics
Influenza
Herpes
HPV
Influenza (flu) virus is a ss, RNA, enveloped virus
(Fig. 23.21) that infects cells of the respiratory
tract.
Continually evolving
The Neuraminidase (N) protein on the viral surface
hydrolyzes the host mucous coating allowing the
Variants (via mutations and genetic
rearrangement) of last year’s virus
Hemagglutinin (H) to bind to protein receptors on
mucosal cells
H changes slightly
New strain(s) every year
H becomes new antigen not recognized by last
year’s antibodies
The virus is taken up and H fuses with the
membrane
New “shot” every year
causing the viral RNA to be released into the
cytoplasm
Influenza--Humanity evolution arms race
Major rearrangements (antigenic shift)
"antigenic drift" = year to year minor
variations (mutations) in the viral membrane
proteins
"antigenic shift" = major changes in these
proteins
Major change was cause of deadly pandemics
(e.g. 1918 and 1957)
-more than one strain of flu
-infect a single cell at the same time
Thus during assembly of the viruses
-eight different segments of the viral genome
-mixed and matched into new viruses
-major new antigenic presentation
See
Possible genetic rearrangement among duck,
swine and human flu viruses (probably in
pigs)
Fig. 23.22
> Influenza caused worst world pandemic in
1918-1919, killing over 20 million people (about
80% of the American casualties during WWI)
Herpes
> Viruses are inhaled or ingested. Spread via
sneezing and coughing
See
Fig. 14.13
!Results in fever, chills, headache, aches
!Most of the symptoms are caused by virus
lysis (bursting) cells of the respiratory tract
!leads to secondary infections by bacteria and
other viruses
> Death occurs due to secondary infections
> 10,000-40,000 deaths due to flu every year
Genital Warts
HPV of genital warts
are related to HPVs that cause cancer
probably most common sexually transmitted
disease. (pp. 654-655)
HPV-16
Cause = human papillomavirus (HPV)
in the USA = 7% of all cancers in females
naked viruses resistant to drying
At least 50 different HPVs cause tumors
(malignant and/or benign)
Warts are benign tumors
--> cervical cancer
(5000
deaths annually). PAP test detects early.
HPVs are ds DNA viruses
incorporated into host chromosome or becomes
plasmid
cause infected cell to multiply more rapidly than
normal --> tumor
HPV Prevention/Treatment
Cancer causing Papillomaviruses code for
proteins that inhibit anti-oncogenes
Worrisome pandemic of genital warts -->
Cancer causing forms just as easily
transmitted as wart-causing
Both often both found in women with
cervical cancer
• No sex with people with warts (duh)
• Condoms
• Avoid sex with people with multiple
partners
• PAP tests regularly
• Wart removal DOES NOT cure cancer
causing infection
HIV
pp. 739-749
The Toll of AIDS
More than 33 million people infected
worldwide
16 million have died
!First described in 1981-83
!Epidemiologists predicted a blood-borne
virus
Fourth leading cause of death in the world.
!1984 - Gallo linked a retrovirus to
immunodeficiency syndrome, AIDS
Fig. 29.1
AIDS pandemic
as of 2001
Fig. 29.9. Percentage of AIDS cases in women in
the USA.
Human Immunodeficieny Viruses
Retrovirus - ss RNA
infect mononuclear phagocytes
HIV targets cells with CD4 receptors
See Fig. 29.3.
Life Cycle of HIV
Fig. 29.6
The Three Phases of HIV Disease
HIV infection--most infected cells show
•no lysis (bursting)
•no latency (integrated genome, no virus
produced)
•accumulating and releasing viral products
(integrated genome)
Fig. 29.8 Blood levels of
•HIV virus--red
•circulating HIV RNA--green
•CD4 cells--blue
Epidemiology of HIV
Transmitted via:
• sexual intercourse
• blood and blood products
• mother to infant
Vaccine?
No vaccine for HIV (yet)
HIV constantly changing its proteins
(evolution)
“Sloppy” reverse transcriptase-->high
mutation rates-->high evolution rate
Problems with HAART
Treatment
Antiviral “cocktails”
Drug toxicity and inconvenience.
HAART = “highly active anti-retroviral therapy” =
Expense.
Mixture of inhibitors:
Viral Drug Resistance.
-reverse transcriptase (e.g. AZT)
Residual Virus Replication. HIV continues to replicate
because drugs do not penetrate all
tissues/compartments.
PLUS
Long-Lived Reservoirs of Virus Infection.
-protease
Combined therapy especially effective. Why?
Prions
- infectious protein particles
- cause diseases in animals and humans
- Prions--the only infectious agents that do NOT
contain any nucleic acids
- Cause brain diseases in
-sheep (scrapie)
-cows (mad cow disease, BSE)
-humans (Kuru and Creutzfeld-Jakob disease)
-elk/deer (Chronic Wasting Disease)
(see Table 14.12).
- Result of prion diseases = holes in brain tissue,
sponge-like appearance (thus "spongiform
encephalitis")
- All caused by exposure to brains
- Kuru was figured out by Gajdusek
- spread via burial ceremonies
- people smeared brains of dead relatives on
their bodies
Mad Cow Disease
BSE
-bovine spongiform encephalopathy (BSE)
-British added ground up sheep & cows to cattle feed
latent period up to 15 years
-cattle then ground up and fed to humans (burgers!)
? long time before full impact on people in
Britain is known
-Prions are not destroyed by cooking
detected recently (2003) in a cow in the USA
-incidence of Creutzfeld-Jakob disease in humans
recently increased in Britain
Clin Lab Med. 2002 Dec; 22(4):849-862
Emerging Infectious Diseases
Vol. 10, Number 6, June 2004
Variant Creutzfeldt-Jakob disease and bovine
spongiform encephalopathy.
Belay, E.D., and L.B. Schonberger.
Abstract:
Strong epidemiologic and laboratory evidence indicate that a novel,
variant form of Creutzfeldt-Jakob disease (vCJD) first reported in
the United Kingdom in 1996 is causally linked with bovine
spongiform encephalopathy (BSE). BSE was first identified in the
early 1980s in the United Kingdom, and has since spread to other
European countries and recently to Japan and Israel. Although the
United Kingdom BSE epizootic is on the decline, widespread
exposure of humans to infected cattle products may have
already occurred, raising concerns about the ultimate magnitude of
the vCJD outbreak which, as of October 2002, has already affected
138 patients worldwide, including 128 patients in the United Kingdom.
Chronic Wasting Disease and Potential Transmission to Humans
E.D. Belay, R. A. Maddox, E.S. Williams, M. W. Miller, P. Gambetti, and L.B. Schonberger
Chronic wasting disease (CWD) of deer and elk is endemic in a tri-corner area
of Colorado, Wyoming, and Nebraska, and new foci of CWD have been
detected in other parts of the United States. Although detection in some areas
may be related to increased surveillance, introduction of CWD due to
translocation or natural migration of animals may account for some new foci of
infection. Increasing spread of CWD has raised concerns about the potential for
increasing human exposure to the CWD agent. The foodborne transmission
of bovine spongiform encephalopathy to humans indicates that the
species barrier may not completely protect humans from animal prion
diseases. Conversion of human prion protein by CWD-associated prions
has been demonstrated in an in-vitro cell-free experiment, but limited
investigations have not identified strong evidence for CWD transmission to
humans. More epidemiologic and laboratory studies are needed to monitor the
possibility of such transmissions.
Figure. Chronic wasting disease among free-ranging
deer and elk by county, United States.
How do prions cause disease and replicate
without nucleic acids?
First idea--inducers or repressors of gene
expression
The latest theory--recruit proteins similar to
themselves in the membranes of brain cells
From: E.D. Belay, R. A. Maddox, E.S. Williams, M. W. Miller, P. Gambetti, and
L.B. Schonberger. 2004. Chronic Wasting Disease and Potential Transmission
to Humans Emerging Infectious Diseases 10(6), June 2004
Proposed
mechanism for
prion replication
Beneficial Microbes
- prions line up next to similar
proteins that line brain cells
- cause a shift in their tertiary
structure to the prion form
- causes the outer lining of brain
cells to become rigid and cavity
forming…….
•
•
•
•
•
•
Cyanobacteria--atmospheric O2
Rhizobium--N fixation, soil fertility
Rumen flora--digest cellulose in horses
E.coli and others--protective intestinal flora
Mitochondrion--ATP
Etc.
Fig 14.22
Discussion Question
Are viruses always harmful?
Are they ever beneficial?
Brainstorm ideas
•Small groups
•3 to 5 people per group
•5 minutes to meet
•Compile group’s ideas--spokesperson
QUESTION: in what ways could
viruses be beneficial?
Ideas
• Protection against disease
– Vaccinia
• Ecological
– Australian rabbits and viral eco-control
• Host modification
– Turn on anti-oncogenes
– Manipulate gene expression
• As vectors
– Transfer useful genes to other hosts
– Gene therapy
• Target viruses to kill tumor cells