ch13 Flashcards
virus
A virus is a minuscule, acellular, infectious agent usually
having one or several pieces of nucleic acid—either DNA or
RNA
what do viruses lack
- cytoplasmic membrane
- cysotol and functional organelles
- not capable of metabolic activity on their own
Viruses have an extracellular and an intracellular state.
- outside: virion = capsic + nucleic acid (maybe envelope)
- inside: capsid removed, just nucleic acid
capsid
Basically, a virion consists of a protein
coat, called a capsid, surrounding a nucleic acid core.
- The capsid of a virus is
composed of proteinaceous subunits called capsomeres (or capsomers).
Some capsomeres are composed of only a single type of
protein, whereas others are composed of several different kinds
of proteins.
envelope
Some virions have
a phospholipid membrane called an envelope surrounding
the nucleocapsid. The outermost layer of a virion (capsid or
envelope) provides the virus both protection and recognition
sites that bind to complementary chemicals on the surfaces
of their specific host cells.
generalists
By contrast, some viruses are generalists;
they infect many kinds of cells in many different hosts.
An example of a generalist virus is West Nile virus
viruses were first identified
from tobacco plants
fungal viruses
- exist only within cells; that is, they seemingly
have no extracellular state. - Presumably, fungal viruses
cannot penetrate a thick fungal cell wall. However, because
fusion of cells is typically a part of a fungal life cycle, viral infections
can easily be propagated by
nucleocapsid
Together the nucleic acid and its capsid are
also called a nucleocapsid, which in many cases can crystallize
like crystalline chemicals
viral shapes
- helical
- polyhedral (most common: icosahedron - 20 sides)
- complex
matrix proteins
viral proteins called matrix proteins fill the region between
capsid and envelope.
much-studied virus
dsDNA phage of e coli called type 4 (T4). T4 virions are complex, having
the polyhedral heads and helical tails seen in many bacteriophages.
lytic replication cycle
- the cell undergoes lysis near the end of the cycle
- AESAR: attachment, entry, synthesis, assembly, release
attachment
- Because phages, like all virions, are nonmotile, contact with a
bacterium occurs by purely random collision - The structures responsible for the attachment
of T4 to its host bacterium are its tail fibers - Attachment
is dependent on the chemical attraction and precise fit between
attachment proteins on the phage’s tail fibers and complementary
receptor proteins on the surface of the host’s cell wall
entry
- Upon contact with E. coli, T4
releases lysozyme, a protein enzyme carried within
the capsid that weakens the peptidoglycan of the cell wall. - phage’s tail sheath then conctracts, forcing a tube within the tail through the cell wall and membrane
- phage injects genome thru tube and into bacteria
- empty capsid left outside
viral enzymes
are either carried within the capsid or
coded by viral genes and made by the bacterium
synthesis
- viral enzymes degrade bacterial DNA into its constituent nucleotides; As a result, the
bacterium stops synthesizing its own molecules and begins
synthesizing new viruses under control of the viral genome. - Translation by the host cell’s ribosomes results
in viral proteins, including head capsomeres, components of
the tail, viral DNA polymerase (which replicates viral DNA),
and lysozyme (which weakens the bacterial cell wall from
within, enabling the virions to leave the cell once they have
been assembled).
assmelby
- viral assembly is a spontaneous process, requiring little
or no enzymatic activity
transduction
Sometimes a capsid assembles around leftover pieces of
host DNA instead of viral DNA. A virion formed in this manner
is still able to attach to a new host by means of its tail fibers,
but instead of inserting phage DNA, it transfers DNA from the
first host into a new host. This process is known as transduction
release
Newly assembled virions are released from the cell as lysozyme
completes its work on the cell wall and the bacterium disintegrates.
burst time
For any phage undergoing
lytic replication, the period of time required to complete
the entire process, from attachment to release, is called the
burst time
burst size
the number of new virions released from each
lysed bacterial cell is called the burst size
lysogeny
- Some bacteriophages have a modified replication
cycle in which infected host cells grow and reproduce normally
for many generations before they lyse. - temperate / lysogenic phages
much-studied temperate phage
lambda phage
- another e coli parasite
lysogenic conversion
Lysogenic phages can change the phenotype of a bacterium,
for example from a harmless form into a pathogen—a process
called lysogenic conversion.
prophage
temperate phage enters cell and remains inactive. Such an inactive bacteriophage is
called a prophage. A prophage remains inactive by
coding for a protein that suppresses prophage genes. (One prophage gene codes for a protein that prevents transcription
of most of the other prophage genes.) A side effect
of this repressor protein is that it renders the bacterium resistant
to additional infection by other viruses of the same type.
- the prophage is inserted into the DNA of the bacterium, becoming
a physical part of the bacterial chromosome
induction
when the lambda genome is induced to exit the bacterial chromosome (by recombination?)
and initiate a lytic cycle. Inductive
agents are typically the same physical and chemical agents
that damage DNA molecules, including ultraviolet light, X rays,
and carcinogenic chemicals.
- After induction, the lytic steps of synthesis, assembly,
and release resume from the point at which they stopped. The
cell becomes filled with virions and breaks open.
lysogenic vs lytic
lysogenic: The viral DNA enters the cell, just as occurs with phage
T4, but the host cell’s DNA is not destroyed, and the phage’s genome
does not immediately assume control of the cell.
bacteriophages vs animal viruses: structure
Unlike the bacteriophages we have examined, animal
viruses lack both tails and tail fibers. Instead, animal viruses
typically have glycoprotein spikes or other attachment molecules
on their capsids or envelopes.
animal virus entry mechanisms
at least three different
mechanisms: direct penetration, membrane fusion, and
endocytosis.
direct penetration
Some naked viruses enter their hosts’ cells by direct
penetration—a process in which the viral capsid attaches and
sinks into the cytoplasmic membrane, creating a pore through
which the genome alone enters the cell.
membrane fusion
- the entire capsid
and its contents (including the genome) enter the host cell - viral envelope and the
host cell membrane fuse, releasing the capsid into the cell’s
cytoplasm and leaving the envelope glycoproteins as part of the
cell membrane
endocytosis
- the entire capsid
and its contents (including the genome) enter the host cell - Attachment of the virus to receptor
molecules on the cell’s surface stimulates the cell to endocytize
the entire virus
uncoating
For those viruses that penetrate a host cell with their capsids
intact, the capsids must be removed to release their genomes
before the viruses can continue to replicate. The removal of a
viral capsid within a host cell is called uncoating, a process that
remains poorly understood. (membrane fusion and endocytosis)
DNA vs RNA animal viruses
DNA viruses typically enter the nucleus,
whereas most RNA viruses are replicated in the cytoplasm.
animal dsDNA virus synthesis
After messenger RNA is transcribed from viral DNA in the nucleus
and capsomere proteins are made in the cytoplasm by host
ribosomes, capsomeres enter the nucleus, where new virions
spontaneously assemble.
animal ssDNA virus synthesis
Cells do not use
ssDNA, so when a parvovirus enters the nucleus of a host cell,
host enzymes produce a new strand of DNA complementary
to the viral genome. This complementary strand binds to the
ssDNA of the virus to form a dsDNA molecule. everything else same
parvovirus
- A human virus with a genome composed of
single-stranded DNA (ssDNA) is a parvovirus. - prominent one: causes contagious disease in dogs
types of rna viruses
There are four types of RNA viruses:
positive-sense, single-stranded RNA (designated +ssRNA);
retroviruses (a kind of +ssRNA virus); negative-sense, singlestranded
RNA (−ssRNA); and double-stranded RNA (dsRNA).
+RNA
Single-stranded viral RNA that can
act directly as mRNA is called positive-strand RNA (+RNA). Ribosomes translate polypeptides using the codons of such
RNA.
-RNA
in many +ssRNA viruses, a complementary negative-strand RNA (−RNA)
is transcribed from the +ssRNA genome by viral RNA polymerase;
-RNA then serves as the template for the transcription of
multiple +ssRNA genomes. Such transcription of RNA from RNA
is unique to viruses; no cell transcribes RNA from RNA.
retroviruses
- a kind of +ssRNA virus
- don’t use their genome as mRNA
- use reverse transcriptase (carried in capsid) to synthesize DNA from +RNA
- this DNA serves as the template for more +RNA molecules, which act both as mRNA
for protein synthesis and as genomes for new virions - HIV
-ssRNA
In order to synthesize a protein, a ribosome can use only mRNA
(i.e., +RNA) because −RNA is not recognized by ribosomes. The
virus overcomes this problem by carrying within its capsid an
enzyme, RNA-dependent RNA transcriptase, which is released into
the host cell’s cytoplasm during uncoating and then transcribes
+RNA molecules from the virus’s −RNA genome. Translation of
proteins can then occur as usual. The newly transcribed +RNA
also serves as a template for transcription of additional copies of −
RNA
dsRNA
The positive strand of the molecule
serves as mRNA for the translation of proteins, one of which
is an RNA polymerase that transcribes dsRNA. Each strand of
RNA acts as a template for transcription of its opposite, which is
reminiscent of DNA replication in cells
persistent infectioin graph
!!!!!!
persistent infections
Infections with enveloped viruses in which
host cells shed viruses slowly and relatively steadily are called
persistent infections; a curve showing virus abundance over time
during a persistent infection lacks the burst of new virions seen
in lytic replication cycles
budding
Enveloped animal viruses are often released via a process
called budding. As virions are assembled, they
are extruded through one of the cell’s membranes—the nuclear,
endoplasmic reticulum, or the cytoplasmic membrane. Each
virion acquires a portion of membrane, which becomes the
viral envelope.
- During synthesis, some viral glycoproteins are inserted into cellular membranes, and these proteins become
the glycoprotein spikes on the surface of the viral envelope.
- Because the host cell is not quickly lysed, as occurs in bacteriophage
replication, budding allows an infected cell to remain
alive for some time
releasing naked animal viruses
Naked animal viruses may be released in one of two ways:
Either they may be extruded from the cell by exocytosis, in a
manner similar to budding but without the acquisition of an
envelope, or they may cause lysis and death of the cell, reminiscent
of bacteriophage release.
one reason it is difficult to treat viral diseases
Because viral replication uses cellular structures and pathways
involved in the growth and maintenance of healthy cells,
any strategy for the treatment of viral diseases that involves
disrupting viral replication may disrupt normal cellular processes
as well.
latency
Some animal viruses, including chicken pox and herpes viruses,
may remain dormant in cells in a process known as latency; the
viruses involved in latency are called latent viruses or proviruses.
Latency may be prolonged for years with no viral activity,
signs, or symptoms. Though latency is similar to lysogeny
as seen with bacteriophages, there are differences. Some latent
viruses do not become incorporated into the chromosomes of
their host cells, whereas lysogenic phages always do.
provirus
On the other hand, some animal viruses (e.g., HIV) are more
like lysogenic phages in that they do become integrated into a
host chromosome as a provirus. However, when a provirus is incorporated
into its host DNA, the condition is permanent; induction
does not occur in eukaryotes
neoplasia
if something upsets the genetic control, cells begin to divide uncontrollably.
This phenomenon of uncontrolled cell division in a multicellular animal is called neoplasia.
tumor
a mass of
neoplastic cells is a tumor.
benign
Some tumors are benign; that is, they remain in one place
and are not generally harmful, although occasionally such noninvasive
tumors are painful and rob adjacent normal cells of
space and nutrients.
malignant
Other tumors are malignant, invading
neighboring tissues and even traveling throughout the body to
invade other organs and tissues to produce new tumors—a process
called metastasis. Malignant tumors are also
called cancers. Cancers rob normal cells of space and nutrients
and cause pain; in some kinds of cancer, malignant cells derange
the function of the affected tissues, until eventually the body can
no longer withstand the loss of normal function and dies.
protooncogenes
genes that play a role in cell division. As long as protooncogenes
are repressed, no cancer results. However, activity of oncogenes
(their name when they are active) or inactivation of oncogene
repressors can cause cancer to develop.
Viruses cause __% to __% of human cancers in several
ways:
20 - 25
Some viruses carry copies of oncogenes as part of their
genomes, other viruses promote oncogenes already present in
the host, and still other viruses interfere with normal tumor repression
when they insert (as proviruses) into repressor genes.
Virologists have developed three types of media
for culturing viruses:
media consisting of mature organisms
(bacteria, plants, or animals), embryonated (fertilized) eggs, and
cell cultures.
culturing viruses in bacteria
Phages can be grown in bacteria maintained either in liquid cultures
or on agar plates. In the latter case, bacteria and phages
are mixed with warm (liquid) nutrient agar and poured in a
thin layer across the surface of an agar plate. During incubation,
bacteria infected by phages lyse and release new phages
that infect nearby bacteria, while uninfected bacteria grow and
reproduce normally
plaques
After incubation, the appearance of the
plate includes a uniform bacterial lawn interrupted by clear
zones called plaques, which are areas where phages have lysed
the bacteria.
plaque assay
Such plates enable the estimation of
phage numbers via a technique called plaque assay, in which
virologists assume that each plaque corresponds to a single
phage in the original bacterium-virus mixture.
Culturing Viruses in Chicken Eggs
Chicken eggs are a useful culture medium for viruses because
they are inexpensive, are among the largest of cells, are free of
contaminating microbes, and contain a nourishing yolk (which
makes them self-sufficient). Most suitable for culturing viruses
are chicken eggs that have been fertilized and thus contain a
developing embryo. Embroyonic tissues (called membrans) provide
ideal inoculation sites for growing viruses.
2 types of cell cultures
diploid and continuous
diploid cell cultures
are created from embryonic animal, plant, or human
cells that have been isolated and provided appropriate growth
conditions. The cells in diploid cell culture generally last no
more than about 100 generations (cell divisions) before they die.
continuous cell cultures
are
longer lasting because they are derived from tumor cells.
viroids
Viroids are extremely small, circular pieces of RNA that are infectious
and pathogenic in plants. Viroids are similar to
RNA viruses except that they lack capsids. Even though they are
circular, viroids may appear linear because of hydrogen bonding
within the molecule.
viroidlike agents
Viroidlike agents—infectious, pathogenic RNA particles that
lack capsids but do not infect plants—affect some fungi.
prions
a proteinaceous infectious
agent that was different from any other known infectious
agent in that it lacked instructional nucleic acid.
PrP
All mammals make a cytoplasmic membrane protein
called PrP. PrP is anchored in lipid rafts and plays a role in
the normal activity of the brain, though the exact function of
PrP is unknown. The amino acid sequence in PrP is such that
the protein can fold into two stable tertiary structures: The normal, functional structure of cellular PrP has several prominent
α-helices, whereas a disease-causing form—prion PrP—is
characterized by β-pleated sheets.
how
can prions carry the information required to replicate themselves?
Scientists have determined that prion PrP acts like a bad influence
in a crowd of teenagers, encouraging molecules of normal,
cellular PrP to misbehave by refolding into prion PrP molecules,
which then clump together.
prion diseases
As clumps of prion PrP propagate
throughout the brain, neurons stop working properly and eventually
die, leaving holes and a spongy appearance.
Because of this characteristic, clinicians call prion diseases spongiform encephalopathies.
Why don’t prions develop in all mammals, given that all
mammals have PrP?
Under normal circumstances, it appears
that other nearby proteins and polysaccharides in lipid rafts
force PrP into the correct (cellular) shape. Mutations in the PrP
gene can result in the initial formation of prion PrP, but human
cellular PrP visually misfolds only if it contains methionine as
the 129th amino acid.
Prions are associated with several diseases:
including bovine
spongiform encephalitis (BSE, so-called mad cow disease),
scrapie in sheep, kuru (a human disease that has been eliminated),
chronic wasting disease (CWD) in deer and elk, and variant
Creutzfeldt-Jakob disease (vCJD) in humans.
deactivating prions
Normal cooking or sterilization procedures do not deactivate
prions, though they are destroyed by incineration or by
autoclaving in concentrated sodium hydroxide.
