Download Chapter 13 Viruses General Characteristics of all viruses

Chapter 13
Viruses
General Characteristics of all viruses
• Contain a single type of nucleic acid (DNA
or RNA)
• Contains a protein coat that surrounds the
nucleic acid
– Capsid: most of mass of cell
(subunit=capsomers)
– May be enclosed by envelope (part of host’s
plasma membrane); may be covered with
spikes
Viruses
• Obligate intracellular parasites
– Inert outside of living tissue (host)
– In host Æ nucleic acids active and multiply
• Are viruses the only obligate intracellular
parasites?
• Most viruses infect only specific types of
cells in one host; Host range is determined
by specific host attachment sites and
cellular factors
1
Medical Significance
• Most agents that would interfere with viral
multiplication would also harm the host
cells and would be very toxic
History began with the Tobacco
Mosaic Virus (TMV)
• 1886 Aldolf Mayer
showed that a virus
was transmissable
between plants
• 1892 Iwanowski tried
to isolate it by filtering
with porcelain filter
Sizes of viruses
2
Polyhedral virus
• Capsid coat made of
capsomeres
• Nucleic acid inside
Helical virus with an envelope
• The shape is a long
rod
• Rabies and Ebola are
helical viruses
• Influenzae virus is
helical with an
envelope
Helical Viruses
Figure 13.4a, b
3
Bacteriophage: Complex virus
Bacterial viruses
•
•
Known as bacteriophages or phages
Two different life cycles
1. Lytic cycle-results in lysis of the cell
2. Lysogenic cycle-may result in lysis of the
cell or the virus becomes a permanent part
of the chromosome by integrating
(Lytic Cycle)
• Attachment
• Penetration
• Biosynthesis
• Maturation
• Release
Phage attaches by tail fibers to
host cell
Phage lysozyme opens cell wall,
tail sheath contracts to force tail
core and DNA into cell
Production of phage DNA
and proteins
Assembly of phage particles
Phage lysozyme breaks cell wall
4
Lytic Cycle
• Burst Time: time from phage attachment to
release (about 20 -40 min)
• Burst size: number of new phages
released from a single cell (50 – 200)
Lytic Cycle
Lytic Cycle
5
Growth curve of bacteriophage
Lysogenic Cycle
• Lysogenic (temperate)
– Phage may result in lysis of cell
– Virus may integrate into host chromosome and
become permanent part of cell
• Phage remains inactive within lysogenic host
cells
• Cells then immune to reinfection by same
virus
• Phage conversion: host cell may have new
characteristics due to phage
Lysogenic Cycle
6
Specialized
transduction
Bacterial DNA
Prophage gal gene
1 Prophage exists in galactose-using host
(containing the gal gene).
Galactose-positive
donor cell
gal gene
2 Phage genome excises, carrying
with it the adjacent gal gene from
the host.
gal gene
3 Phage matures and cell lyses, releasing
phage carrying gal gene.
4 Phage infects a cell that cannot utilize
galactose (lacking gal gene).
Galactose-negative
recipient cell
5 Along with the prophage, the bacterial gal
gene becomes integrated into the new
host’s DNA.
6 Lysogenic cell can now metabolize
galactose.
Galactose-positive recombinant cell
Figure 13.13
How can you study
bacteriophages?
• Plaque assay
-pour agar with
bacteria and phage
on top of an agar
plate
-“plaque” develops
where virus infected
bacterial cell
-each plaque is
counted as one virus
Growing Animal Viruses
• Animal
viruses may
be grown in
living animals
or in
embryonated
eggs.
Figure 13.7
7
Growing Viruses
• Animal and plants viruses may be grown
in cell culture.
– Continuous cell lines may be maintained
indefinitely.
Figure 13.8
Virus Identification
• Cytopathic effects(CPE): can count like
plaques
• Serological tests
– Detect antibodies against viruses in a patient
– Use antibodies to identify viruses in
neutralization tests, viral hemagglutination, and
Western blot
• Nucleic acids
Cytopathic Effect of Viruses
Figure 13.9
8
Multiplication of Animal viruses
• Attachment Viruses attaches to cell
membrane (receptors are inherited)
• Penetration By endocytosis or fusion
• Uncoating
By viral or host enzymes
• Biosynthesis Production of nucleic acid and
proteins
• Maturation
Nucleic acid and capsid proteins
assemble
• Release
By budding (enveloped viruses)
or rupture (usually results in cell death)
Attachment, Penetration, and
Uncoating
Figure 13.14
Release of an enveloped virus
by budding
Figure 13.20
9
DNA
Papovavirus
1 Virion attaches to host cell
7 Virions are released
Host cell
DNA
Capsid
2 Virion penetrates
DNA
cell and its DNA is
uncoated
Cytoplasm
6 Virions mature
Capsid proteins
mRNA
5 Late translation;
capsid proteins
are synthesized
4 Late transcription;
DNA is replicated
3 Early transcription and
translation; enzymes are
synthesized
Figure 13.15
RNA Virus Multiplication
• RNA viruses differ in how mRNA produced
+ single stranded RNA can serve as mRNA to code for
proteins
= single stranded RNA does not code for proteins
Retroviruses: reverse transcriptase
RNA
Figure 13.17
10
Retrovirus
Capsid
Reverse
transcriptase
DNA
Virus
Two identical + stands of RNA
1 Retrovirus penetrates
host cell.
Host
cell
DNA of one of the host
cell’s chromosomes
5 Mature
retrovirus
leaves host
cell, acquiring
an envelope as
it buds out.
Reverse
transcriptase
Viral RNA
Identical
strands of
RNA
2 Virion penetrates
cell and its DNA is
uncoated
4 Transcription of the
provirus may also occur,
producing RNA for new
retrovirus genomes and
RNA that codes for the
retrovirus capsid and
envelope proteins.
Viral proteins
RNA
Provirus
3 The new viral DNA is
tranported into the host cell’s
nucleus and integrated as a
provirus. The provirus may
divide indefinitely with the
host cell DNA.
Figure 13.19
• Latent Viral Infections
– Virus remains in asymptomatic host cell for long
periods
• Cold sores, shingles
• Persistent Viral Infections
– Disease processes occurs over a long period,
generally fatal
• Subacute sclerosing panencephalitis (measles virus)
Virus Families
• Single-stranded DNA,
nonenveloped viruses
– Parvoviridae
• Human parvovirus
• Fifth disease
– Anemia in
immunocompromised
patients
11
Double-stranded DNA,
nonenveloped viruses
• Mastadenovirus
– Respiratory
infections in
humans
– First isolated in
adenoids
– Tumors in
animals
Double-stranded DNA,
nonenveloped viruses
• Papillomavirus
(human wart
virus)
• Polyomavirus
– Cause tumors,
some cause
cancer
Double-stranded DNA,
nonenveloped viruses
• Orthopoxvirus
(vaccinia and
smallpox viruses/
variola)
• Molluscipoxvirus
– Smallpox,
molluscum
contagiosum,
cowpox
12
DNA Animal Viruses
• Poxviridae
– dsDNA, enveloped
– small pox virus
(variola)
• Simplexvirus (HHV1 and
HHV 2)
• Varicellavirus (HHV 3)
• Lymphocryptovirus (HHV 4)
• Cytomegalovirus (HHV 5)
• Roseolovirus (HHV 6)
• HHV 7
• Kaposi's sarcoma (HHV 8)
– Some herpesviruses can
remain latent in host cells
Herpes simplex-1
• HHV-1 causes fever
blisters, HHV-2
genital herpes
• Symptoms: fluid filled
skin lesions
• Treatment: Acyclovir
13
Varicella (chickenpox) and
Herpes Zoster (Shingles)
• HHV-3 causes
chicken pox and
latent activation
known as shingles
• Acquired by
respiratory route, 2
weeks later see
vesicles on skin
• Vaccine established
in 1995 for
chickenpox
Epstein Barr
• Causes infectious
mononucleosis
• Acquire by saliva,
incubation period is 4-7
weeks
• Identify by
-lobed lymphocytes
-heterophile antibodies
-fluorescent antibody
tests
Double-stranded DNA,
nonenveloped viruses
• Hepadnavirus
(Hepatitis B virus)
– Use reverse
transcriptase to
produce DNA
from mRNA
14
Hepadnaviridae
• dsDNA, enveloped
• Hepatitis B
-passes through
intermediate stage (RNA)
-three particles in blood
Dane
filamentous
sphericle
-exposure through
blood/body fluids
Hepatitis B
• Incubation period is ~12 weeks
• 10% of cases become chronic, mortality
rate is less than 1%
• About 40% of the chronic cases die of liver
cirrhosis
RNA animal viruses
• Is there an enzyme in animal cells to
replicate RNA?
• What does RNA polymerase do?
15
RNA animal viruses
• (+) single stranded RNA viruses
– RNA serves as mRNA to code for proteins
• (-) single stranded RNA viruses
– RNA does not code for proteins
RNA
Figure 13.17
Single-stranded RNA, + strand,
nonenveloped
• Enterovirus
– Enteroviruses
include poliovirus
and
coxsackievirus
• Rhinovirus
• Hepatitis A virus
16
Picornaviridae (+) ssRNA
• Poliovirus
• Virus ingested then travels throughout the body
• In some cases it impairs the upper motor neurons,
less than 1% of all cases
• Vaccines
– Salk vaccine (IPV)
– Enhanced-inactivated polio (E-IPV)
– Sabin vaccine
Cases of Poliomyelitis in US
Picornaviridae (+) ssRNA
• Rhinovirus
-causes the common cold
-100 or more serological types
-virus grows best in the nose and
conjunctiva
17
Picornaviridae (+) ssRNA
• Enterovirus responsible for 90% of viral
gastroenteritis
– Rotavirus
• Most common cause of viral gastroenteritis
– Norwalk-like virus
• Responsible for local epidemics
Rotavirus
• Note the shape which
gave it the name
rota=wheel
Picornaviridae (+) ssRNA
• Hepatitis A
-obtain through fecal-oral route, enters GI tract
and multiplies
-incubation period is ~4 weeks
-symptoms include: anorexia, malaise, nausea,
diarrhea, abdominal discomfort, fever, and chills
lasting 2-21 days
18
Single-stranded RNA, + strand,
nonenveloped
• Arboviruses can
replicate in
arthropods; include
yellow fever, dengue,
SLE, and West Nile
viruses
• Hepatitis C virus
Flaviviridae (+) ssRNA, enveloped
• Hepatitis C virus
– Obtain from blood/body fluids
– Incubation period averages 6 weeks
– Hard to screen blood for the virus
– 85% of all cases become chronic
Single-stranded RNA, – strand,
one RNA strand
• Vesiculovirus
• Lyssavirus
(rabies virus)
– Cause numerous
animal diseases
19
Rhabdoviridae (-)ssRNA,
enveloped
• Rabies virus
-enters the skin and multiplies in skeletal
muscle and connective tissue
-virus travels along nerves to the CNS
causing encephalitis
Pathology of rabies
Single-stranded RNA, – strand,
one RNA strand
• Filovirus
– Enveloped,
helical viruses
– Ebola and
Marburg
viruses
20
Single-stranded RNA, – strand,
one RNA strand
• Paramyxovirus
• Morbillivirus
– Paramyxovirus
causes
parainfluenza,
mumps and
Newcastle
disease
• Influenzavirus
(Influenza viruses
A and B)
• Influenza C virus
– Envelope spikes
can agglutinate
RBCs
Orthomyxoviridae-multiple
strands of (-)RNA
• Influenza virus
– Consists of 8 segments of RNA
– Envelope has H spikes (hemagglutinin) and N
spikes (neuraminidase)
– Incubation is 1-3 days
– Symptoms include: chills, fever, headache,
muscle aches, may lead to cold-like
symptoms
21
Influenza virus
Identical (+) strands RNA
• Lentivirus (HIV)
• Oncogenic
viruses
– Use reverse
transcriptase to
produce DNA
from viral
genome
– Includes all RNA
tumor viruses
Retroviridae-multiple strands of
(+)RNA
• HIV
22
Retroviruses
• HIV, Hepatitis B
• Reverse
Transcriptase
Retrovirus
Capsid
Reverse
transcriptase
DNA
Virus
Two identical + stands of RNA
1 Retrovirus penetrates
host cell.
Host
cell
DNA of one of the host
cell’s chromosomes
5 Mature
retrovirus
leaves host
cell, acquiring
an envelope as
it buds out.
Reverse
transcriptase
Viral RNA
Identical
strands of
RNA
2 Virion penetrates
cell and its DNA is
uncoated
4 Transcription of the
Viral proteins
RNA
provirus may also occur,
producing RNA for new
retrovirus genomes and
RNA that codes for the
retrovirus capsid and
envelope proteins.
Provirus
3 The new viral DNA is
tranported into the host cell’s
nucleus and integrated as a
provirus. The provirus may
divide indefinitely with the
host cell DNA.
Figure 13.19
Cancer
• Activated oncogenes transform normal cells
into cancerous cells.
• Transformed cells have increased growth,
loss of contact inhibition, tumor specific
transplant and T antigens.
• The genetic material of oncogenic viruses
becomes integrated into the host cell's DNA.
23
Oncogenic Viruses
• Oncogenic RNA
viruses
• Oncogenic DNA
Viruses
– Retroviridae
– Adenoviridae
– Heresviridae
– Poxviridae
– Papovaviridae
– Hepadnaviridae
• Viral RNA is
transcribed to DNA
which can integrate
into host DNA
• HTLV 1
• HTLV 2
Prions
• Infectious proteins
• Inherited and transmissible by ingestion,
transplant, & surgical instruments
• Spongiform encephalopathies: Sheep scrapie,
Creutzfeldt-Jakob disease, GerstmannSträussler-Scheinker syndrome, fatal familial
insomnia, mad cow disease
• PrPC, normal cellular prion protein, on cell
surface
• PrPSc, scrapie protein, accumulate in brain
cells forming plaques
Prions
PrPSc
PrPc
1
2
3
4
Lysosome
Endosome
5
6
7
8
Figure 13.21
24