Download DNA viruses - WordPress.com

Document related concepts

Ebola virus disease wikipedia , lookup

Viral phylodynamics wikipedia , lookup

Social history of viruses wikipedia , lookup

Virus wikipedia , lookup

Oncolytic virus wikipedia , lookup

Bacteriophage wikipedia , lookup

DNA virus wikipedia , lookup

HIV wikipedia , lookup

Introduction to viruses wikipedia , lookup

Virus quantification wikipedia , lookup

Endogenous retrovirus wikipedia , lookup

History of virology wikipedia , lookup

Papillomaviridae wikipedia , lookup

Plant virus wikipedia , lookup

Negative-sense single-stranded RNA virus wikipedia , lookup

Virology wikipedia , lookup

Transcript
9.1 General Properties of Viruses
• Virus: genetic element that cannot replicate
independently of a living (host) cell
• Virology: the study of viruses
• Virus particle (virion): extracellular form of a virus
– Exists outside host and facilitates transmission
from one host cell to another
– Contains nucleic acid genome surrounded by a
protein coat and, in some cases, other layers of
material
© 2012 Pearson Education, Inc.
9.1 General Properties of Viruses
• Viral Genomes (Figure 9.1)
– Either DNA or RNA genomes
– Some circular, but most linear
© 2012 Pearson Education, Inc.
Figure 9.1
Viral Class
Viral Genome
DNA viruses
ssDNA
© 2012 Pearson Education, Inc.
dsDNA
RNA viruses
ssRNA
dsRNA
RNA  DNA
viruses
ssRNA
(Retroviruses)
dsDNA
(Hepadnaviruses)
9.2 Nature of the Virion
• Viral Structure
– Capsid: the protein shell that surrounds the
genome of a virus particle (Figure 9.2)
• Composed of a number of protein molecules
arranged in a precise and highly repetitive
pattern around the nucleic acid
– Capsomere: subunit of the capsid
• Smallest morphological unit visible with an
electron microscope
© 2012 Pearson Education, Inc.
Figure 9.2
18 nm
Structural subunits
(capsomeres)
Virus RNA
© 2012 Pearson Education, Inc.
9.2 Nature of the Virion
• Viral Structure (cont’d)
– Nucleocapsid: complete complex of nucleic acid
and protein packaged in the virion (Figure 9.3)
– Enveloped virus: virus that contains additional
layers around the nucleocapsid
© 2012 Pearson Education, Inc.
Figure 9.3
Envelope
Nucleocapsid
Capsid
Nucleic
acid
Nucleic
acid
Capsid
(composed of
capsomeres)
Naked virus
© 2012 Pearson Education, Inc.
Enveloped virus
9.2 Nature of the Virion
• Nucleocapsids constructed in highly symmetric
ways
– Helical symmetry: rod-shaped viruses (e.g.,
tobacco mosaic virus)
• Length of virus determined by length of nucleic
acid
• Width of virus determined by size and packaging
of protein subunits
– Icosahedral symmetry: spherical viruses
(e.g., human papillomavirus; Figure 9.4)
• Most efficient arrangement of subunits in a closed
shell
© 2012 Pearson Education, Inc.
Figure 9.4
5-Fold
3-Fold
Symmetry
Cluster of
5 units
© 2012 Pearson Education, Inc.
2-Fold
9.2 Nature of the Virion
• Enveloped Viruses (Figure 9.5a)
– Have membrane surrounding nucleocapsid
• Lipid bilayer with embedded proteins
– Envelope makes initial contact with host cell
• Complex Viruses (Figure 9.5b)
– Virions composed of several parts, each with
separate shapes and symmetries
– Bacterial viruses contain complicated structures
• Icosahedral heads and helical tails
© 2012 Pearson Education, Inc.
Figure 9.5
Head
Collar
Tail
Tail pins
Endplate
Tail fibers
© 2012 Pearson Education, Inc.
9.2 Nature of the Virion
• Some virions contain enzymes critical to infection
– Lysozyme
• Makes hole in cell wall
• Lyses bacterial cell
– Nucleic acid polymerases
– Neuraminidases
• Enzymes that cleave glycosidic bonds
• Allows liberation of viruses from cell
© 2012 Pearson Education, Inc.
9.3 The Virus Host
• Viruses replicate only in certain types of cells or
in whole organisms
• Bacterial viruses are easiest to grow; model
systems
• Animal viruses (and some plant viruses) can be
cultivated in tissue or cell cultures
• Plant viruses typically are most difficult because
study often requires growth of whole plant
© 2012 Pearson Education, Inc.
9.4 Quantification of Viruses
• Titer: number of infectious units per volume
of fluid
• Plaque assay: analogous to the bacterial colony;
one way to measure virus infectivity (Figure 9.6)
– Plaques are clear zones that develop on lawns of
host cells
• Lawn can be bacterial or tissue culture (Figure 9.7)
• Each plaque results from infection by a single virus
particle
© 2012 Pearson Education, Inc.
Figure 9.6
Pour mixture onto
solidified nutrient
agar plate
Mixture containing
molten top agar,
bacterial cells, and
diluted phage
suspension
Nutrient agar
plate
Let solidify
Sandwich of top
agar and
nutrient agar
Incubate
Phage
plaques
© 2012 Pearson Education, Inc.
Lawn of host
cells
Plaques
9.5 General Features of Virus Replication
• Phases of Viral Replication (Figure 9.8)
– Attachment (adsorption) of the virus to a
susceptible host cell
– Entry (penetration) of the virion or its nucleic acid
– Synthesis of virus nucleic acid and protein by cell
metabolism as redirected by virus
– Assembly of capsids and packaging of viral
genomes into new virions (maturation)
– Release of mature virions from host cell
© 2012 Pearson Education, Inc.
Figure 9.8
Protein coat
remains outside
Virion
DNA Attachment
(adsorption)
Cell (host)
Penetration
(injection)
Viral DNA enters
Synthesis of
nucleic acid
and protein
Assembly and
packaging
Release
(lysis)
Virions
© 2012 Pearson Education, Inc.
9.5 General Features of Virus Replication
• Virus replication typically characterized by a
one-step growth curve (Figure 9.9)
• Latent period: eclipse + maturation
• Burst size: number of virions released
© 2012 Pearson Education, Inc.
Figure 9.9
Maturation
Relative virus count
(plaque-forming units)
Eclipse
Early
enzymes
Nucleic
acid
Virus
added
Latent period
Time
© 2012 Pearson Education, Inc.
Protein
coats
Assembly
and
release
9.6 Viral Attachment and Penetration
• Attachment of virion to host cell is highly specific
– Requires complementary receptors on the
surface of a susceptible host and its infecting
virus
– Receptors on host cell carry out normal functions
for cell (e.g., uptake proteins, cell to cell
interaction)
– Receptors include proteins, carbohydrates,
glycoproteins, lipids, lipoproteins, or complexes
© 2012 Pearson Education, Inc.
9.6 Viral Attachment and Penetration
• The attachment of a virus to its host cell
results in changes to both virus and cell
surface that facilitate penetration
• Permissive cell: host cell that allows the
complete replication cycle of a virus to occur
© 2012 Pearson Education, Inc.
9.6 Viral Attachment and Penetration
• Bacteriophage T4: virus of E. coli; one of the most
complex penetration mechanisms (Figure 9.10)
– Virions attach to cells via tail fibers that interact
with polysaccharides on E. coli cell envelope
– Tail fibers retract and tail core makes contact with
E. coli cell wall
– Lysozyme-like enzyme forms small pore in
peptidoglycan
– Tail sheath contracts and viral DNA passes into
cytoplasm
© 2012 Pearson Education, Inc.
Figure 9.10
Tail
fibers
Tail pins
Outer
membrane
Tail
lysozyme
Peptidoglycan
Cytoplasmic
membrane
Cytoplasm
T4 genome
© 2012 Pearson Education, Inc.
9.6 Viral Attachment and Penetration
• Many eukaryotes possess mechanisms to
diminish viral infections
– For example, immune defense mechanisms,
RNA interference
• Prokaryotes also possess mechanisms
– CRISPR
• Similar to RNA interference
– Restriction modification system
© 2012 Pearson Education, Inc.
9.6 Viral Attachment and Penetration
• Restriction modification systems (cont’d)
– DNA destruction system; only effective
against double-stranded DNA viruses
– Restriction enzymes (restriction
endonucleases) cleave DNA at specific
sequences
– Modification of host’s own DNA at restriction
enzyme recognition sites prevents cleavage
of own DNA
© 2012 Pearson Education, Inc.
9.6 Viral Attachment and Penetration
• Viral mechanisms to evade bacterial restriction
systems
– Chemical modification of viral DNA (glycosylation
or methylation)
– Production of proteins that inhibit host cell
restriction system
© 2012 Pearson Education, Inc.
Figure 9.11
dsDNA () virus
Class I
Class VII
ssDNA ()
virus
dsRNA ()
virus
ssRNA ()
virus
ssRNA ()
virus
ssRNA ()
retrovirus
Class II
Class III
Class IV
Class V
Class VI
Synthesis of
other strand
dsDNA intermediate
Transcription
of minus strand
Used directly
as mRNA
Transcription
of minus strand
Reverse
transcription
Transcription
of minus strand
Transcription
of minus strand
mRNA ()
mRNA ()
Genome
replication: Class I, classical semiconservative
Class II, classical semiconservative,
discard () strand
Class VII, transcription followed by
DNA viruses
reverse transcription
© 2012 Pearson Education, Inc.
dsDNA intermediate
Genome
replication: Class III, make ssRNA () and transcribe from this to give ssRNA () partner
Class IV, make ssRNA () and transcribe from this to give ssRNA () genome
Class V, make ssRNA () and transcribe from this to give ssRNA () genome
Class VI, make ssRNA () genome by transcription of () strand of dsDNA
RNA viruses
9.7 Production of Viral Nucleic Acid
and Protein
• Once a host has been infected, new copies of the
viral genome must be made and virus-specific
proteins synthesized in order for the virus to
replicate
• Generation of messenger RNA (mRNA) occurs
first
• Viral genome serves as template for viral mRNA
• In some RNA viruses, viral RNA itself is the mRNA
• In some cases essential transcriptional enzymes
are contained in the virion
© 2012 Pearson Education, Inc.
9.7 Production of Viral Nucleic Acid
and Protein
• Nomenclature used to describe mRNA is used to
describe the configuration of the genome of a
single-stranded DNA or RNA virus (mRNA is said
to be in plus (+) configuration; its complement is
in minus () configuration)
– Positive-strand RNA virus: single-stranded RNA
genome with same orientation as its mRNA
– Negative-strand RNA virus: single-stranded RNA
genome with orientation complementary to its
mRNA
© 2012 Pearson Education, Inc.
9.7 Production of Viral Nucleic Acid
and Protein
• Retroviruses: animal viruses responsible for
causing certain types of cancers and
acquired immunodeficiency syndrome (AIDS)
– Class VI and VII viruses
– Require reverse transcriptase
© 2012 Pearson Education, Inc.
9.7 Production of Viral Nucleic Acid
and Protein
• Viral Proteins
– Production follows synthesis of viral mRNA
• Early proteins
– synthesized soon after infection
– necessary for replication of virus nucleic acid
– typically act catalytically
– synthesized in smaller amounts
© 2012 Pearson Education, Inc.
9.7 Production of Viral Nucleic Acid
and Protein
• Production of Viral Proteins (cont’d)
– Late proteins
•
•
•
•
Synthesized later
Include proteins of virus coat
Typically structural components
Synthesized in larger amounts
© 2012 Pearson Education, Inc.
9.8 Overview of Bacterial Viruses
• Bacteriophages are very diverse (Figure 9.12)
• Best-studied bacteriophages infect enteric
bacteria
– Examples of hosts: E. coli, Salmonella enterica
• Most phages contain dsDNA genomes
• Most are naked, but some possess lipid
envelopes
• They are structurally complex, containing heads,
tails, and other components
© 2012 Pearson Education, Inc.
Figure 9.12
RNA
ss
MS2
ds
6
ssDNA
174
fd, M13
dsDNA
T3, T7
Mu
Lambda
© 2012 Pearson Education, Inc.
T2, T4
9.10 Temperate Bacteriophages, Lambda,
and P1
• Temperate viruses: can undergo a stable genetic
relationship within the host (Figure 9.16)
– But can also kill cells through lytic cycle
• Lysogeny: state where most virus genes are not
expressed and virus genome (prophage) is
replicated in synchrony with host chromosome
• Lysogen: a bacterium containing a prophage
• Under certain conditions lysogenic viruses may
revert to the lytic pathway and begin to produce
virions
© 2012 Pearson Education, Inc.
Figure 9.16
Temperate virus
Host DNA
Viral DNA
Attachment
Cell (host)
Injection
Lytic pathway
Lysogenic pathway
Viral DNA
replicates
Induction
Coat proteins
synthesized;
virus particles
assembled
Viral DNA
is integrated
into host DNA
Lysogenized cell
Prophage
Lysis
© 2012 Pearson Education, Inc.
Cell
division
Figure 9.17
Capsid
Tail
© 2012 Pearson Education, Inc.
9.11 Overview of Animal Viruses
• Entire virion enters the animal cell, unlike in
prokaryotes
• Eukaryotic cells contain a nucleus, the site of
replication for many animal viruses
• Animal viruses contain all known modes of viral
genome replication (Figure 9.21)
• Many more kinds of enveloped animal viruses
than enveloped bacterial viruses exist
– As animal viruses leave host cell, they can
remove part of host cell’s lipid bilayer for their
envelope
© 2012 Pearson Education, Inc.
Figure 9.21
Nonenveloped
Enveloped
ssDNA
Parvovirus
Nonenveloped
Enveloped all ssRNA
partially
dsDNA
Hepadnavirus
dsDNA
Papovavirus
dsDNA
ssRNA
Picornavirus
Rhabdovirus
Togavirus
Orthomyxovirus
dsDNA
Poxvirus
Adenovirus
dsRNA
dsDNA
Bunyavirus Coronavirus
Reovirus
100 nm
dsDNA
Herpesvirus
Iridovirus
DNA viruses
© 2012 Pearson Education, Inc.
Paramyxovirus
100 nm
Arenavirus Retrovirus
RNA viruses
9.11 Overview of Animal Viruses
• Consequences of Virus Infection in Animal Cells
(Figure 9.22)
– Persistent infections: release of virions from host
cell does not result in cell lysis
• Infected cell remains alive and continues to
produce virus
– Latent infections: delay between infection by the
virus and lytic events
– Transformation: conversion of normal cell into
tumor cell
– Cell fusion: two or more cells become one cell
with many nuclei
© 2012 Pearson Education, Inc.
Figure 9.22
Tumor
Transformation
cell
division
Transformation
into tumor cell
Lysis
Cell
Death of
cell and
release
of virus
Attachment
and penetration
Persistent
infection
Virus
multiplication
Cell
fusion
Slow release
of virus without
cell death
Latent
infection
Virus present
but not replicating
© 2012 Pearson Education, Inc.
May revert to lytic infection
Virus
9.12 Retroviruses
• Retroviruses: RNA viruses that replicate
through a DNA intermediate
– Enveloped viruses (Figure 9.23a)
– Contain a reverse transcriptase (copies
information from its RNA genome into DNA),
integrase, and protease
– Virion contains specific tRNA molecules
© 2012 Pearson Education, Inc.
Figure 9.23a
Surface envelope protein
RNA
Enzymes
(reverse
transcriptase,
integrase,
protease)
Lipid
membrane
bilayer
Core shell
protein
Core protein
© 2012 Pearson Education, Inc.
Transmembrane
envelope protein
9.12 Retroviruses
• Retroviruses have a unique genome
– Two identical ssRNA molecules of the plus (+)
orientation
– Contain specific genes (Figure 9.23b)
• gag: encode structural proteins
• pol: encode reverse transcriptase and
integrase
• env: encode envelope proteins
© 2012 Pearson Education, Inc.
9.12 Retroviruses
• Process of Replication of a Retrovirus (Figure
9.24)
– Entrance into the cell
– Removal of virion envelope at the membrane
– Reverse transcription of one of the two RNA
genomes
– Integration of retroviral DNA into host genome
– Transcription of retroviral DNA
– Assembly and packaging of genomic RNA
– Budding of enveloped virions; release from cell
© 2012 Pearson Education, Inc.
Figure 9.24
Retrovirus virion
containing ssRNA
(two copies)
Entrance
Uncoating
R
R
ssRNA
Reverse transcription
LTR
dsDNA
LTR
Travel to nucleus and
integration into host DNA
Host DNA
LTR Provirus
LTR
Transcription
R
R Viral mRNA and
genomic RNA
ssRNA
Encapsidation
ssRNA
Nucleocapsid
Budding
Host cytoplasmic
membrane
Release
Progeny
retrovirus virions
© 2012 Pearson Education, Inc.
IV. Subviral Entities
• 9.13 Defective Viruses
• 9.14 Viroids
• 9.15 Prions
© 2012 Pearson Education, Inc.
9.13 Defective Viruses
• Defective viruses: viruses that are parasitic
on other viruses
– Require other virus (helper virus) to provide
some function
• Some rely on intact virus of same type
• Satellite viruses: defective viruses for which
no intact version exists; rely on unrelated
viruses as helpers
© 2012 Pearson Education, Inc.
9.14 Viroids
• Viroids: infectious RNA molecules that lack a
protein coat
– Smallest known pathogens (246–399 bp)
– Cause a number of important plant diseases
(Figure 9.25)
– Small, circular, ssRNA molecules (Figure 9.26)
– Do not encode proteins; completely dependent
on host-encoded enzymes
© 2012 Pearson Education, Inc.
Figure 9.25
© 2012 Pearson Education, Inc.
Figure 9.26
© 2012 Pearson Education, Inc.
9.15 Prions
• Prions: infectious proteins whose extracellular
form contains no nucleic acid
– Known to cause disease in animals (transmissible
spongiform encephalopathies)
– Host cell contains gene (PrnP) that encodes
native form of prion protein that is found in healthy
animals (Figure 9.28)
– Prion misfolding results in neurological symptoms
of disease (e.g., resistance to proteases,
insolubility, and aggregation)
© 2012 Pearson Education, Inc.
Figure 9.28
Neuronal cell
Nucleus
Prnp
DNA
Transcription
Translation
Normal
function
PrPc
(normal prion)
PrPSc-induced
misfolding
PrPSc
(misfolded prion)
© 2012 Pearson Education, Inc.
Abnormal
function
9.15 Prions
• Prion disease occurs by three distinct
mechanisms:
– Infectious prion disease: pathogenic form of
prion protein is transmitted between animals
or humans
– Sporadic prion disease: random misfolding of
a normal, healthy prion protein in an
uninfected individual
– Inherited prion disease: mutation in prion
gene yields a protein that changes more often
into disease-causing form
© 2012 Pearson Education, Inc.