Prescott’s Microbiology, 9th Edition
27
Viruses
CHAPTER OVERVIEW
This chapter describes the life cycles of viruses of all types and specificities. Viruses are grouped by the type
of genome they possess and the details of replication for each type is given. Important examples from each
group are used for illustration and to introduce broader concepts such as latency and virulence.
LEARNING OUTCOMES
After reading this chapter you should be able to:
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distinguish between the Baltimore system of grouping viruses and the official taxonomy of viruses
proposed by the International Committee on Taxonomy of Viruses
determine if a virus has a positive- or negative-strand genome
differentiate the Baltimore group of viruses
describe in general terms the strategy used by double-stranded (ds) DNA viruses to synthesize their
nucleic acids and proteins
describe in general terms how bacteriophage lambda regulates the switch between the lytic and lysogenic
cycles
choose one specific bacterial, archaeal, and eukaryal dsDNA virus and outline the major events in their
life cycles, noting, when possible, the specific mechanisms used to accomplish each step
describe in general terms the strategy used by single-stranded (ss) DNA viruses to synthesize their nucleic
acids and proteins
choose one specific bacterial and eukaryal ssDNA virus and illustrate the major events in their life cycles,
noting, when possible, the specific mechanisms used to accomplish each step
identify which RNA viruses use RNA-dependent RNA polymerases and which use DNA-dependent RNA
polymerases to complete their life cycles
describe the different approaches used by RNA viruses to synthesize the proteins they need to complete
their life cycles
propose how a virus with a single RNA molecule as its genome might generate multiple proteins from that
molecule
describe in general terms the strategy used by dsRNA viruses to synthesize their nucleic acids and proteins
describe the major events in the life cycles of and rotaviruses, noting, when possible, the specific
mechanisms used to accomplish each step
describe in general terms the strategy used by plus-strand RNA viruses to synthesize their nucleic acids
and proteins
outline the major events in the life cycles of poliovirus and tobacco mosaic virus, noting, when possible,
the specific mechanisms used to accomplish each step
describe in general terms the strategy used by minus-strand RNA viruses to synthesize their nucleic acids
and proteins
explain how having a segmented genome impacts synthesis of viral mRNA and proteins and the generation
of new strains of a virus
create a flow chart that summarizes the life cycle of influenza virus, noting the specific mechanisms it uses
to accomplish each step of its life cycle
describe in general terms the strategy used by retroviruses to synthesize their nucleic acids and proteins
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Prescott’s Microbiology, 9th Edition
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differentiate a segmented genome from the genome of a retrovirus
describe in general terms the strategy used by reverse transcribing DNA viruses to synthesize their nucleic
acids and proteins
compare the role of reverse transcriptase in the life cycle of a retrovirus to that in the life cycle of a
hepadnavirus
CHAPTER OUTLINE
I.
II.
Virus Taxonomy and Phylogeny
A. Almost 2,000 viral species have been placed in 3 orders, 73 families, and 287 genera; genome type,
capsid structure, and envelope are used for classification
B. Some viruses are known to possess positive- or negative-strand RNA or DNA genomes, while
others have double-stranded DNA or RNA genomes; seven groups of viruses are defined by life
cycle, and this system is used here
C. While some evolutionary relationships are emerging through comparative genomics, it remains
difficult to follow viral phylogenies
Double-Stranded DNA Viruses
A. Largest group of known viruses; mainly bacteriophages with dsDNA genomes; includes
herpesviruses and poxviruses; rely on host DNA and RNA polymerases
B. Bacteriophage T4: A virulent bacteriophage
1. Virulent phages can only undergo the lytic cycle in several stages
a. Attachment (adsorption) and penetration
1) Viruses attach to specific receptor sites on the host cell using tail fibers and
baseplate settles on surface
2) Tail sheath contracts, injecting DNA into the host cell, leaving an empty capsid
outside
b. Synthesis of phage nucleic acids and proteins
1) mRNA molecules transcribed early in the infection (early mRNA) are synthesized
using host RNA polymerase; early proteins, made at the direction of early mRNA
molecules, direct the synthesis of protein factors and enzymes required to take over
the host cell
2) Transcription of viral genes then follows an orderly sequence due to the
modification of the host RNA polymerase and changes in sigma factors
3) Later in the infection viral DNA is replicated using a virus-encoded DNA
polymerase
(i) Synthesis of viral DNA requires the initial synthesis of alternate bases; these are
used to protect the phage DNA from host enzymes (restriction endonucleases) that
would otherwise degrade the viral DNA and thereby protect the host
(ii) T4 can form concatemers (long chains) of the DNA genome are formed; these are
later cleaved during assembly
c. Assembly of phage particles
1) Late mRNA molecules (those made after viral nucleic acid replication) direct the
synthesis of capsid proteins and other proteins involved in assembly (e.g.,
scaffolding proteins) and release of the virus
2) Assembly proceeds sequentially by subassembly lines, which assemble different
structural units (e.g., baseplate, tail tube); these are then put together to make the
complete virion
3) DNA packaging is accomplished with a protein complex called the packasome,
which includes the terminase complex that fills in gaps at the end of concatemers
d. Release of phage particles—host is lysed by damaging the cell wall or the cytoplasmic
membrane with T4 lysozyme and holin enzyme
C. Bacteriophage lambda: A temperate bacteriophage
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Prescott’s Microbiology, 9th Edition
1.
D.
E.
F.
Temperate phages are capable of lysogeny, a nonlytic relationship with their hosts (virulent
phages lyse their hosts)
a. In lysogeny, the viral genome (called a prophage) remains in the host (usually integrated
into the host chromosome) but does not kill (lyse) the host cell; the cells are said to be
lysogenic (or are called lysogens)
b. It may switch to the lytic cycle at some later time; this process is called induction
2. Most bacteriophages are temperate; it is thought that being able to lysogenize bacteria is
advantageous; supporting this is the observation that certain conditions favor the establishment
of lysogeny
3. Lysogenic conversion is a change that is induced in the host phenotype by the presence of a
prophage, and that is not directly related to the completion of the viral life cycle; examples
include:
a. Modification of lipopolysaccharide structure in infected Salmonella
b. Production of diphtheria toxin only by lysogenized strains of Corynebacterium
diphtheriae
4. Establishment of lysogeny
a. Two sets of viral promoters are available to host RNA polymerase
b. A repressor protein (lambda repressor) may be made from genes adjacent to one of these
promoters
c. If the lambda repressor binds to its target operator before the other promoter is used, that
promoter is blocked and lysogeny is established
d. If genes associated with that second promoter (Cro protein) are expressed before the
lambda repressor can bind to the operator, the lytic cycle is established
e. Induction (the termination of lysogeny and entry into the lytic cycle) will occur if the
level of lambda repressor protein decreases; this is usually in response to environmental
damage to host DNA
f.
For lambda and most temperate phages, if lysogeny is established, the viral genome
integrates into the host chromosome; however, some temperate phages can establish
lysogeny without integration
Archaeal viruses
1. All known archaeal viruses have dsDNA genomes; some have unusual morphologies
2. Some archaeal viruses are virulent, while others are temperate
3. Many Archeae and eubacteria have developed a mechansim to defend against viruses known
as the CRISPR/Cas system
a. Clustered regularly interspaced short palindromic repeats (CRISPR)
b. Regions between repeats have homology to viral genes and may act similar to RNA
silencers to future infections
Herpesviruses
1. Family of human pathogens with dsDNA genome; cause chicken pox, shingles, genital herpes,
cold sores; include cytomegalovirus and Epstein-Barr virus
2. Enveloped pleomorphic virus with spikes; genome contains 50 to 100 genes in an icosahedral
capsid
3. First exposure leads to productive herpes infections that generate many new virions leading to
host cell death; infected neurons develop latent infections that can be reactivated
4. Receptor-mediated viral binding to host cell herpesvirus entry mediators (HVEMs) leads to
capsid penetration and movement of the viral particle to the nucleus; the viral genome is
expressed using host cell machinery and produce early gene products required for replication;
late gene expression directs production of viral proteins
5. Exit from the cell starts with viral budding through the inner nuclear membrane; the virus
moves to the plasma membrane for exocytosis in an vesicle derived from the Golgi
Nucleo-cytoplasmic large DNA (NCLD) viruses
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Prescott’s Microbiology, 9th Edition
1.
A group of large enveloped icosahedral virions with a large dsDNA genome that includes
members from several virus families (e.g., Poxviridae and Phycodnaviridae); some are the size
of small bacteria
2. Large genome houses many genes needed for viral replication and assembly
3. Poxviruses are large brick-shaped virions with a dumbbell-shaped core; enter through
receptor-mediated endocytosis; early and late genes are expressed during the life cycle
III. Single-Stranded DNA Viruses
A. Bacteriophages X174 and fd
1. X174 is plus-strand DNA virus—virus genome that has the same sequence as the viral
mRNA
a. The single-stranded genome is converted to a double-stranded replicative form (RF) by
the host DNA polymerase
b. The RF directs synthesis of more RF, RNA, and +strand DNA genome
c. Phages are released by lysis of host cell
2. Filamentous phage fd—plus-strand DNA virus
a. Phage DNA enters via the host cell’s sex pilus and an RF is synthesized
b. The RF directs mRNA synthesis and DNA replication via the rolling-circle method
c. Phages are released without lysing the host cell; instead they are released by a secretory
process
B. Parvoviruses
1. Group of viruses of eukaryotic cells, including Human parvovirus B19
2. Naked icosahedral virions with mainly negative-strand DNA genomes; among simplest DNA
viruses, codes for no enzymatic proteins
3. Enter by receptor-mediated endocytosis and move to the nucleus; viral genomes have
palindromic ends that act as sites for DNA polymerase binding and rolling-circle replication
IV. RNA Viruses: Unity Amidst Diversity
A. Many viruses with RNA genomes carry RNA-dependent RNA polymerase (replicase), an enzyme
not found in host cells
V. Double-Stranded RNA Viruses
A. Bacteriophage 6
1. Enveloped dsRNA virus with segmented genome; uses pilus for entry through fusion with the
outer membrane, viral enzymes degrade peptidoglycan allowing entry
2. Inside host, viral RNA polymerase generates mRNA and viral genomes; host cells are lysed to
release mature virions
B. Rotaviruses
1. Human pathogens causing severe diarrhea; survive in the environment
2. Naked dsRNA viruses with a segmented genome and a wheel-like capsid with three-layers of
proteins
3. Outer protein layer lost during penetration releasing double-layered particle (DLP); viral genes
expressed and viral proteins accumulate in cytoplasmic inclusions called viroplasm; viral
envelope arises from endoplasmic reticulum
VI. Plus-Strand RNA Viruses
A. Replicate in host cell cytoplasm using viral RNA-dependent RNA polymerase to generate
replicative form; progeny viruses assembled in replication complexes; includes most plant viruses
and some human pathogens
B. Bacteriophages MS2 and Q—small, tailless, icosahedral virions with very simple genomes; use
pili to reach cell membrane and then insert genome; uses viral RNA polymerase to generative
replicative form and produce new virions that are released by host cell lysis
C. Poliovirus
1. Naked plus-strand RNA virus causes polio in humans
2. Enters host cell by ingestion; genome acts as mRNA but without a 5' cap an internal ribosome
binding site mediates recognition
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Prescott’s Microbiology, 9th Edition
3.
A polyprotein is produced that self-cleaves into capsid proteins, RNA polymerase, and others;
mature virions are released through host cell lysis
D. Tobacco mosaic virus (TMV)
1. Plant viruses are mainly plus-strand RNA viruses
2. TMV is a helical filamentous virion that resembles animal viruses and bacteriophages
a. Penetration through the plant cuticle through wounds or by the action of biting insects
b. The virus uses either a cellular or a virus-specific RNA-dependent RNA polymerase
c. The virus produces proteins, which then spontaneously assemble
d. Viral spread is through the plant vascular system or to adjacent cells through
plasmodesmata
e. The virus causes many cytological changes, such as the formation of inclusion bodies and
the degeneration of chloroplasts
VII. Minus-Strand RNA Viruses
A. Spherical or pleomorphic, enveloped virions having segmented or unsegmented genomes; includes
Rabies virus, Ebola virus, influenza viruses, and Measles virus
B. Must carry RNA-dependent RNA polymerase to generate mRNA from minus-strand RNA genome
C. Influenza
1. Causes three major types of flu; has segmented genome
2. Uses surface neuraminidase and hemagglutinin spikes to enter cells through receptor-mediated
endocytosis; membrane fusion with endosome releases capsid to cytoplasm; mature virions
released through cell lysis
VIII. Retroviruses
A. Contain positive-strand RNA genomes that do not act as mRNA; ssRNA genome converted to
dsDNA using reverse transcriptase; dsDNA genome can then integrate into the host cell
chromosome
B. Human immunodeficiency virus (HIV)
1. Causative agent of AIDS; enveloped virion with two RNA genomes and enzymes including
reverse transcriptase and integrase
2. Surface GP120 protein binds to host CD4+ T-helper cells and other immune cells; entrance is
by receptor-mediated endocytosis
3. Reverse transcriptase copies the RNA genome into dsDNA that integrates as a provirus into
the host cell chromosome; mature viruses bud from host cell surface; eventually the host cell is
killed
IX. Reverse Transcribing DNA Viruses
A. Hepadnaviruses include Hepatitis B virus, a spherical virion with a circular genome
B. One strand of the dsDNA genome is nicked, while the complementary strand has a large gap which
is repaired by host cell enzymes; viral replication involves reverse transcription of progenome RNA
formed from the minus-strand DNA
CRITICAL THINKING
1.
Describe the life cycle of the HIV viruses being sure to include the replication process. Why do you think
that a retrovirus like HIV might be difficult to treat? What features of the viral replication cycle are
unique to the virus and hence could make good targets to anti-HIV drugs?
2.
Describe the differences between temperate and virulent phages. What survival advantages are offered by
each life cycle? How might you expect human disease caused by each class of virus to differ from each
other?
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Prescott’s Microbiology, 9th Edition
3.
Why might an RNA virus like influenza be such a prevalent viral infection in humans?
4.
Would it be advantageous for a virus to damage host cells? if not, then why isn’t damage to the host
avoided? Is it possible that a virus might become less pathogenic when it has been associated with the
host population for a longer time?
CONCEPT MAPPING CHALLENGE
Construct a concept map that illustrates which enzymes are involved in the life cycles of each of the Baltimore
groups of viruses and how those enzymes are used. Use the concepts that follow or any other concepts or
terms needed to link the concepts in your map. Provide examples of the viruses that utilize each of these
enzymes.
DNA-dependent DNA polymerase Transcriptase
DNA-dependent RNA polymerase
Replicase
RNA dependent RNA polymerase
Integrase
RNA-dependent DNA polymerase
Protease
Excisionase
Reverse transcriptase
RNAseH
Recombinase
Lysozyme
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in any manner. This document may not be copied, scanned, duplicated, forwarded, distributed, or posted on a website, in whole or part.