Microbiology #3
6.1 Viruses in Ecosystems
A virus is a noncellular particle that must infect a host cell, where it reproduces.
It typically subverts the cell’s machinery and directs it to produce viral particles.
The virus particle, or virion, consists of a single nucleic acid (DNA or RNA) contained within a protective protein capsid.
In more complex viruses, the protective protein may be called a head coat.
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Viruses Infect Cells – 1
Different types of viruses infect different specific host cells.
Usually, the hosts are limited to a particular host range of closely related strains or species.
Bacteriophage = Virus that infects bacteria
It forms a plaque of lysed cells on a lawn of bacteria.
An example of a human virus is the measles virus.
An example of a plant virus is the tobacco mosaic virus (TMV).
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Viruses Infect Cells – 2
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FIGURE 6.2 ■ Virus infections and disease. A. Bacteriophage T2 particles pack in a regular array within an E. coli cell (TEM). B. Bacteriophage infection forms plaques of lysed cells on a lawn of bacteria. C. Measles virions bud out of human cells in tissue culture (TEM). D. Child infected with measles shows a rash of red spots. E. Tobacco leaf section is packed with tobacco mosaic virus particles. F. Tomato leaf infected by tobacco mosaic virus shows mottled appearance.
Viruses Infect Cells – 3
But what happens after a virus infects a cell?
A remarkable view of viral replication emerges from fluorescence microscopy.
For an RNA virus, such as hepatitis C virus, virions are assembled within “virus factories,” virus-induced cell compartments called a replication complex.
The complexes move around within the cell.
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FIGURE 6.3 ■ Replication complexes of hepatitis C virus. Membranous replication complexes surround the nucleus of an infected liver cell in tissue culture. The virus expresses replication proteins fused to a fluorescent protein (GFP), shown pink.
Integrated Viral Genomes
Some viruses do more than replicate within a cell; they integrate their genomes into that of the host.
In effect, such viruses become a part of the host organism.
A virus that integrates its genome into the DNA of a bacterial genome is called a prophage.
Within a human cell, an integrated viral genome is called a provirus.
A permanently integrated provirus transmitted via the germ line is called an endogenous virus.
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Dynamic Nature of Viruses – 1
We now know that a virus may interconvert among three very different forms:
Virion, or virus particle – An inert particle that does not carry out any metabolism or energy conversion
Intracellular replication complex – Within a host cell, the viral gene products direct the cell’s enzymes to assemble progeny virions at “virus factories” called replication complexes.
Viral genome integrated within host DNA – This may be a permanent condition.
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Dynamic Nature of Viruses – 2
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FIGURE 6.4 ■ Virus as a subcellular organism. The virion, or virus particle, consists of a nucleic acid genome contained by a protein capsid. A virion may infect a host cell and cause the cell’s enzymes to synthesize progeny virions. Alternatively, infection may lead to integration of the viral genome within the host cell genome. Integration may last indefinitely, or else may lead to production of virions.
Viral Ecology – 1
While viruses are the tiniest of biological entities, they play starring roles in ecosystems.
Acute viruses (which rapidly kill their hosts) act as predators or parasites to limit host population density.
They also recycle nutrients from their host bodies.
Virus-associated mortality may increase the genetic diversity of host species.
Persistent viruses remain in hosts, where they may evolve traits that confer positive benefits in a virus-host mutualism.
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Viral Ecology – 2
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FIGURE 6.5 ■ The relationship of polydnaviruses, wasps, and caterpillars. Parasitoid wasps lay their eggs inside a living insect caterpillar. When a female wasp deposits her eggs inside the caterpillar, she also deposits her symbiogenic polydnavirus virions. The virions express wasp genes in the caterpillar, where they prevent the encapsulation process that would otherwise wall off the wasp egg and kill it.
Viral Disease
Each species of virus infects a particular group of host species, known as its host range.
Some viruses can infect only a single species; for example, HIV infects only humans.
By contrast, West Nile virus, transmitted by mosquitoes, infects many species of birds and mammals.
Chronic viral infections are more common than acute disease.
In contrast to our vast arsenal of antibiotics (effective against bacteria), the number of antiviral drugs remains small.
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6.2 Virus Structure
The structure of a virion keeps the viral genome intact, and it enables infection of the appropriate host cell.
The capsid packages the viral genome and delivers it into the host cell.
Different viruses make different capsid forms.
These can be divided into symmetrical and asymmetrical types.
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Symmetrical Virions – 1
Icosahedral viruses
Are polyhedral with 20 identical triangular faces
Have a structure that exhibits rotational symmetry
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FIGURE 6.7 ■ Herpes: icosahedral capsid symmetry. A. Icosahedral capsid of herpes simplex 1 (HSV-1), with envelope removed. Imaging of the capsid structure is based on computational analysis of cryo-TEM. Images of 146 virus particles were combined digitally to obtain this model of the capsid at 2 nm resolution. B. Icosahedral symmetry includes fivefold, threefold, and twofold axes of rotation. C. The icosahedral capsid contains spooled DNA. Source: A. C. Z. Hong Zhou et al. 1999. J. Virol. 73:3210.
Symmetrical Virions – 2
In some icosahedral viruses, the capsid is enclosed in an envelope, formed from the cell membrane.
The envelope contains glycoprotein spikes, which are encoded by the virus.
Between the envelope and capsid, tegument proteins may be found.
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FIGURE 6.8 ■ Envelope and tegument surround the herpes capsid. A. Section showing envelope and tegument proteins surrounding capsid (cryo-EM). B. Cutaway reconstruction of the herpes virion (cryo-EM tomography).
Symmetrical Virions – 3
Filamentous viruses
The capsid consists of a long tube of protein, with the genome coiled inside.
Vary in length, depending on genome size
Include bacteriophages as well as animal viruses
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FIGURE 6.9 ■ Filamentous viruses. A. Ebola virus filaments (SEM). B. The filamentous bacteriophage M13 has a relatively simple helical capsid that surrounds the genome coiled within (TEM).
Symmetrical Virions – 4
Filamentous viruses show helical symmetry.
The pattern of capsid monomers forms a helical tube around the genome, which usually winds helically within the tube.
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FIGURE 6.10 ■ Tobacco mosaic virus: helical symmetry. A. The helical filament of tobacco mosaic virus (TMV) contains a single-stranded RNA genome coiled inside. B. Components of the TMV virion.
Tailed Viruses
These have complex multipart structures.
T4 bacteriophages
Have an icosahedral “head” and helical “neck”
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FIGURE 6.11 ■ Bacteriophage T4 capsid. A. Phage T4 particle with protein capsid containing packaged double-stranded DNA genome. The capsid has a sheath with tail fibers that facilitate attachment to the surface of the host cell. After attachment, the sheath contracts and the core penetrates the cell surface, injecting the phage genome. B. E. coli infected by phage T4 (colorized blue, TEM).
Asymmetrical Virions – 1
Influenza viruses are RNA viruses that lack capsid symmetry.
Instead, the RNA segments are coated with nucleocapsid proteins.
Poxviruses
Their genome is surrounded by several layers.
A core envelope studded with spike proteins
An outer membrane
Also contain a large number of accessory proteins
These are needed early in viral infection.
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Asymmetrical Virions – 2
Large asymmetrical viruses contain so many enzymes that they appear to have evolved from degenerate cells.
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FIGURE 6.12 ■ Vaccinia poxvirus. A. Vaccinia virion observed in aqueous medium by atomic force microscopy (AFM). B. A pox virion includes an outer membrane and a core envelope membrane containing envelope proteins enclosing the double-stranded DNA genome and accessory proteins. The DNA is stabilized by a hairpin loop at each end.
Viroids
Viroids are RNA molecules that infect plants.
They have no protein capsid.
They are replicated by host RNA polymerase.
Some have catalytic ability.
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FIGURE 6.13 ■ Viroids: infective RNA. Potato spindle tuber viroid consists of a circular single stranded RNA (ssRNA) that hybridizes internally.
Prions
Prions are proteins that infect animals.
They have no nucleic acid component.
They have an abnormal structure that alters the conformation of other normal proteins.
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FIGURE 6.14 ■ Prion disease. A. The normal conformation of a prion, compared to the abnormal conformation. The abnormal form “recruits” normally folded proteins and changes their conformation into the abnormal form. (PDB code: 1AG2) B. Section of a human brain showing “spongiform” holes typical of Creutzfeldt-Jakob disease.
6.3 Viral Genomes and Classification
Viral genomes can be:
DNA or RNA
Single- or double-stranded (ss or ds)
Linear or circular
The form of the genome has key consequences for the mode of infection, and for the course of a viral disease.
Viral genomes are used as the basis of virus classification.
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Viral Genomes: Small
Small viruses commonly have a small genome, encoding under ten genes.
The genes may actually overlap in sequence.
Many small viral genomes consist of RNA.
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FIGURE 6.15 ■ Simple viral genomes. A. Cauliflower mosaic virus has a circular genome of double stranded DNA, whose strands are interrupted by nicks. The genome encodes seven overlapping genes. B. Avian leukosis virus, a single-stranded RNA retrovirus resembling eukaryotic mRNA. Three genes (gag, pol, and env) encode polypeptides that are eventually cleaved to form a total of nine functional products. LTR = long terminal repeat.
Viral Genomes: Large – 1
The “giant viruses” have genomes of double-stranded DNA comprising 500–2,500 genes.
The mimivirus, which infects amoebas, is as large as some bacteria.
It can actually become infected by smaller viruses called virophages.
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FIGURE 6.16 ■ Giant virus infecting an ameba. A. Mimivirus is larger than some bacteria (TEM). B. Sputnik virophage infects Mamavirus, a relative of Mimivirus (TEM).
Viral Genomes: Large – 2
A surprising source of giant viruses is the frozen environments of the Arctic and Antarctic regions.
The Siberian tundra reveals even more remarkable viruses.
Pithovirus
Mollivirus sibericum
Contains parts of a ribosome
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FIGURE 6.17 ■ Giant virus from Siberia. A. The Siberian tundra is melting. B. Pithovirus, a virus as large as E. coli, was isolated from tundra frozen for 30,000 years (TEM).
Viral Genomes: Large – 3
Giant viruses have genomes that specify so many enzymes with housekeeping cell functions.
Such large cell-like genomes suggest the likelihood that a virus evolved from a parasitic cell.
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FIGURE 6.18 ■ Genome of Mimivirus. The genome of this giant virus specifies numerous enzymes with cell functions.
Source: Didier Raoult, et al. Figure from “The 1.2-Megabase Genome Sequence of Mimivirus" Science, 19 Nov 2004: Vol. 306, Issue 5700, pp. 1344-1350. Copyright © 2004, The American Association for the Advancement of Science. Reprinted with permission from AAAS.
The International Committee on Taxonomy of Viruses
The International Committee on Taxonomy of Viruses (ICTV) has devised a classification system, based on several criteria:
Genome composition
Capsid symmetry
Envelope
Size of the virion
Host range
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The Baltimore Virus Classification – 1
In 1971, David Baltimore proposed that the main distinctions among classes of viruses be:
The genome composition (RNA or DNA)
The route used to express messenger RNA (mRNA)
Baltimore would go on to share the 1975 Nobel Prize in Physiology or Medicine for his work
on retroviruses.
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FIGURE 6.19 ■ Baltimore classification of viral genomes. B. David Baltimore (left), with a graduate student at the California Institute of Technology. Baltimore won the 1975 Nobel Prize in Physiology or Medicine for his work on retroviruses; co-winners were Renato Dulbecco and Howard Temin.
The Baltimore Virus Classification – 2
So far, the genome composition and mechanisms of replication and mRNA expression define seven fundamental groups of viral species:
Group I: Double-stranded DNA viruses
Group II: Single-stranded DNA viruses
Group III: Double-stranded RNA viruses
Group IV: (+) single-stranded RNA viruses
Group V: (–) single-stranded RNA viruses
Group VI: RNA retroviruses
Group VII: DNA pararetroviruses
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The Baltimore Virus Classification – 3
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FIGURE 6.19 ■ Baltimore classification of viral genomes. A. Seven categories of viral genome composition and replication mechanism.