Transcript Viruses

Section R – Bacteriophages
and eukaryotic viruses
For example---
Human diseases caused by virus:
AIDS,polio, influenza,cold sores, measles,and
a few types of cancer,…
Plant disease by virus:
tobacco mosaic virus(TMV)
Virion(毒粒，病毒体):
Virus outside of a living cell, exists as
a particle
General features
• Different shapes ,sizes,and
constructions.
• Comprising coat proteins and
nucleotides.
• Obligatory intracellular parasites.
• Containing a small amount of genetic
material( single/double-stranded RNA or
DNA)
Contents
R1 Introduction to viruses
Viruses, Virus genomes, Replication strategies, Virus
virulence
R2 Bacteriophages
General properties, Lytic and lysogenic infection,
Bacteriophage M13, Bacteriophage lambda(λ), Transposable
phages
R3 DNA viruses
DNA genomes: replication and transcription, Small DNA
viruses, Large DNA viruses, Herpes simplex virus-1
R4 RNA viruses
RNA genomes: general features, Viral reverse transcription,
Retroviruses, Oncogenic retroviruses, Retroviral genome
structure and expression, Retroviral mutation rates
R1 Introduction to viruses —
Viruses
• A virus is a sub-microscopic infectious agent
that is unable to grow or reproduce outside a
host cell.
Adenovirus
（腺病毒）
T-even bacteriophage
（T型噬菌体）
Human immunodeficiency
virus(HIV)
Fig. 1. (a) Icosahedral virion (b) Complex bacteriophage with icosahedral
head, and tail (c) Helical virion (d) Enveloped icosahedral virion (e) a
rhabdovirus’ s typical bulletshaped, helical, enveloped icosahedral
R1 Introduction to viruses —
Virus genomes
• Viruses can have genomes consisting of
either RNA or DNA, which may be doublestrand or single-strand, and, for singlestranded genomes, positive, negative or
ambi-sense( defined relative to the mRNA
sequence).
• The genomes vary in size from around 1
kb to nearly 300 kb, and replicate using
combinations of viral and cellular enzyme.
R1 Introduction to viruses —
Replication strategies
•
Viral replication strategies depend largely
on the type and size of genome.
E.g.
1.
2.
3.
Small DNA viruses may make more use of cellular
replication machinery than large DNA viruses,
which often encode their own polymerases.
RNA virus require virus-encoded RNA-dependent
polymerases for their replication.
Some RNA viruses use an RNA-dependent DNA
polymerase( reverse transcriptase) to replicate via
a DNA intermediate.
R1 Introduction to viruses —
Virus virulence
• Many viruses do not cause any cause any
disease, and often the mechanisms of ciral
virulence are accidental to the viral life
cycle, although some may enhance
transmission.
The virulence mechanisms of
viruses fall into six main categories
a. Accidental damage to cellular metabolism
b. Damage to the cell membrane during
transmission between cells.
c. Disease signs important for transmission
between hosts
d. Evasion of the host’s immune system
e. Accidental induction of deleterious immune
responses directed at viral antigens
f. Transformation of cells and tumor formation
R2 Bacteriophages —
General properties
• Bacteriophages infect bacteria.
• In 1915, British bacteriologist Frederick
Twort, superintendent of the Brown
Institution of London, discovered a small
agent that infected and killed bacteria.
R2 Bacteriophages —
Lytic and lysogenic infection
• In lytic infection, virions are released from
the cell by lysis.
• However, in lysogenic viruses integrate
their genomes into that of the host cell,
and may be stably inherited through
several generations before returning to
lytic infection.
R2 Bacteriophages —
Bacteriophage M13
• Bacteriophage M13 has a small singlestranded DNA genomes, replicates via a
double-stranded DNA replicative form, and
can infect cells without causing lysis.
• Modified M13 phage has been used
extensively as a cloning vector.
R2 Bacteriophages —
Bacteriophage lambda(λ)
• Probably the best-studied lysogenic phage
is bactriophageλ.
• Temporally regulated expression of
various groups of genes enables the virus
to either undergo rapid lytic infections, or,
if environmental conditiona are adverse,
undergo lysogeny as a prophage
integrated into the host cell’s genome.
R2 Bacteriophages —
Transposable phages
• Some phage, for example bacteriophage
Mu, routinely integrate into the host cell
and replicative transposition.
R3 DNA viruses —
DNA genomes:
replication and transcription
• DNA virus genomes can be double-stranded .
• Almost all eukaryotic DNA viruses replicate in
the host cell’s nucleus and make use of host
cellular replication and transcription as well as
translation.
• Large dsDNA viruses often have more complex
life cycles, including temporal control of
transcription, translation and replication of both
the virus and the cell.
Viruses with small DNA genome may be more
dependent on the host cell for replication.
R3 DNA viruses —
Small DNA viruses
• One example of a small DNA virus family is the
papovaviridae(乳头多瘤空泡病毒科).
• Papovaciruses, such as SV40 and polyoma(多瘤)
rely on overlapping genes and splicing to
encode six genes in a small, 5kb doublestranded genome.
• These viruses can transactivate cellular
replicative processes which mediate not only
viral but cellar replication; hence they can cause
tumors in their hosts.
R3 DNA viruses —
Large DNA viruses
• Example of large DNA viruses include the
family Herpesviridae(疱疹病毒科).
• Herpesviruses infect a range of
vertebrates(脊椎动物), causing a variety of
important diseases.
R3 DNA viruses —
Herpes simplex virus-1
• Herpes simplex cirus-1(hsv-1) has over 70 open reading
frames (ORFs) and a genome of around 150 kb.
• After infection of a permissive cell, three classes of
genes, the immediate-early (α), early(β) and late(γ)
genes are expressed in a defined temporal sequence.
• These genes express a cascade(串联) of trans-activating
factors which regulate viral transcription and activation.
• This virus has the ability to undergo latent infection(潜伏
性感染).
R4 RNA viruses —
RNA genomes: general features
• Viral RNA genomes may be single- or doublestranded, positive or negative sense, and have a
wide variety of mechanisms of replication.
• All however, rely on virus-encode RNAdependent polymerases, the inaccuracy of
which in terms of making complementary RNA is
much higher than of DNA-dependent
polymerases.
• This significantly affects the evolution of RNA
viruses by increasing their ability to adapt, but
limits their size.
R4 RNA viruses —
Viral reverse transcription
• The use of virus-derived reverse
transcriptases (RTs,逆转录酶) has
revolutionized molecular biology.
3D model of HIV reverse transcriptase
R4 RNA viruses —
Retroviruses
• Reteoviruses have diploid, positive sense
RNA genomes, and replicate via a dsDNA
intermediate.
• This intermediate, called the provirus, is
inserted into the host cell’s genome.
• Retroviruses share many properties with
eukaryotic retrotransposons(反转录转座子)
such as the yeast Ty elements.
Phylogeny of Retroviruses
R4 RNA viruses —
Oncogenic retroviruses
• Insertion of the retrocirus into the host genome
may cause either de-regulation of host cell
genes or, occasionally, may cause
recombination with host cell genes (and the
acquisition of those genes into the viral genome).
• This may give rise to cancer if the retrovirus
alters the expression or activity of a critical cellar
regulatory gene called an oncogene.
R4 RNA viruses —
Retroviral genome
structure and expression
• Retroviral have a basic structure of gag,
pol and env genes flanked by 5’- and 3’long terminal repeats (LTRs).
• The retroviral promoter is found in the U3
region of the 5’LTR and this promoter is
responsible foe all retroviral human
immunodeficiency virus (HIV).
R4 RNA viruses —
Retroviral mutation rates
• The RTs of some retroviruses can have a
high error rate of up to one mutation per
10000 nt.
• Defective genomes may be
complementation and recombination.
• This, combined with the rapid turnover of
virus (109-1010 new virions per day in the
case of HIV), enable it to adapt to
selective pressure.
Multiple choice questions
1. Which one of the following statements about viruses is false?
A viruses can only replicate in a host cell.
B some viral envelopes contain host cell proteins.
C viral genomes may be double stranded or single stranded DNA or RNA.
D replication-defective viruses may be replicated through complementation.
E all viruses are dependent on the host cell replication and transcription machinery.
F some viruses use disease symptoms to aid their transmission between hosts.
2． Which one of the following statements about M13 bacteriophage is true?
A bacterophage M13 has a double stranded DNA genome.
B the M13 phage particle enters the E. coli host cell following binding to the sex pili.
C multiple copies of the M13 replicative form (RF) are produced by normal double
stranded DNA replication using RNA priming.
D M13 phage particles are released by cell lysis.
F there is a highly variable amount of DNA in different M13 phage particles.
3． Which three of the following statements about bacteriophage λ are true?
A the bacteriophage λ has a double stranded DNA genome.
B λ phage particles bind to receptors on the E. coli outer membrane and inject the viral
DNA into the cell.
C the lytic life cycle requires integration of the bacteriophage λ genome into the host cell
genome.
D termination of the N and Cro genes is rho-independent.
E λ repressor acts to repress lysogeny.
F host cell stress tends to switch on the lytic cycle.
4． Which one of the following statements about DNA viruses is false?
A there is often sequence similarity between the promoters of DNA viruses and those of
the host cell.
B the SV40 genome has overlapping reading frames.
C SV40 large T -antigen regulates both viral and host cell transcription and replication.
D the ability of DNA viruses to regulate host cell replication may cause tumors in host
cells.
E SV40 proteins VP1, VP2 and VP3 are important for the tumorigenic properties of the
virus.
5． Which one of the following statements about herpes viruses is true?
A herpes viruses are not associated with tumorigenesis.
B genes are only found on one strand of the herpes virus genome.
C HSV-1 encodes its own DNA polymerase.
D HSV-1 has a single origin of replication.
E latent infection by herpes viruses requires chromosomal integration of the
viral genome.
F all of the herpes viral genes are required for viral replication.
6． Which one of the following statements about retroviruses is false?
A RNA-dependent polymerases are not as accurate as DNA-dependent
polymerases.
B like retroviruses yeast Ty transposons encode a reverse transcriptase
enzyme.
C retroviruses have a single stranded RNA genome.
D the Rev protein of HIV regulates viral transcription.
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