Hi guys! Unfortunately, my document is too big, so i had to split it up in two. This is the second half, consisting of case 5-7 and the practicals. I also made a 'bundle' of the two half docs, so it will consist of the whole document. I hope it will help you guys study. Feel free to contact me if t...
Viruses
1. Icosahedral viruses - made out of equilateral triangles fused
together in a spherical shape that fully encloses the genetic
Viruses are noncellular genetic elements and are obligate1 material. These viruses are released when the cell dies,
intracellular2 parasites as they cannot reproduce outside the host breaks down and lysis. Thus releasing the virions.
cell -> they use a living cell for their replication. 2. Filamentous / helical viruses - have a central cavity or
The simplest viruses consist of a genome of DNA or RNA packaged hollowed tube, which is made by proteins arranged in a
in a protective shell of protein and, for some viruses, a membrane. circular fashion, creating a disc-like shape. The disc shapes
are attached helically, creating room for the nucleic acid in
Viruses differ from bacteria. Bacteria are tiny, single-celled, living
the middle.
organisms that do not depend on a host cell to reproduce. Due to
3. Complex / Head-tail viruses - hybrid between filamentous
these differences, bacterial and viral infections are treated
and icosahedral shapes. These viruses infect bacteria, called
differently. For instance, antibiotics are only helpful against
bacteriophages. They use their tail to attach to the
bacteria, not viruses.
bacterium, create a hole in the cell wall, and insert their DNA.
Structure Virions vs viruses
Certain viruses contain RNA, while other viruses have DNA. The Some virions have a phospholipid membrane with
nucleic acid portion of the virus is known as the viral genome and (glyco)proteins, derived from the host cell, called an envelope,
can be either single-stranded (RNA) or double-stranded (DNA); it which surrounds the nucleocapsid. These viruses are called
may be linear or circular. enveloped viruses. The viruses without an envelope are called
non-enveloped or ‘naked’ viruses (e.g. poliovirus).
The virion (virus in extracellular state (cannot reproduce))
consists of the viral nucleic acid genome packaged into a protein
coat (capsid), which protects the genome and aids in the transfer
between host cells. ● Naked viruses (without envelope)
- are more resistant to extreme conditions: dryness, ranges
Capsid proteins are always encoded by the virus genome,
of pH, different detergents
meaning that it’s the virus (not host cell) that provides instruction
- remain infectious for a longer time on different types of
for making them. -> A capsid is formed from a number of protein molecules
surfaces
called capsomeres, which are arranged in a precise and highly repetitive pattern
around the nucleic acid.
Therefore, these types of viruses are transmitted via surfaces
such as keyboards, toilet seat, public transport, door handles,
Viral adhesion proteins (VAPs) are structures on the surface of
etc.
capsids (and envelope) that mediate the interaction of the virus
● Enveloped viruses (with envelope)
to the target cell. There are two types of VAPs: Hemagglutinin (HA)
- are less resistant to extreme conditions and thus more
and Neuraminidase (NA).
susceptible to these conditions -> because the envelope
The capsid and genome are collectively called the nucleocapsid.
are proteins which are destroyed easy, and the capsid is
The nucleocapsids of viruses often take on of the following shapes
less strong because of the envelope so it is also
(according to the capsid symmetry):
destroyed easy.
Therefore, these types of viruses need to be transmitted
through bodily fluids, sexual intercourse, blood transfusion,
sneezing, needles, etc.
1
Obligate parasites = parasite that depends on the host for nutrition and
reproduction.
Facultative parasites = parasite that only depends on the host for nutrition.
2
Intracellular parasites = are parasites that penetrate the host cells (-> viruses).
Intercellular parasites = parasites present in the extracellular spaces between the
host organism's cells.
, Once inside the cell (intracellular), the capsid
is removed and the virus becomes active. In
this state, the virus exists solely as nucleic
acids. The nucleic acids induce the host to
synthesize viral components, from which
varions are assembled and eventually
released.
In DNA viruses, the viral DNA enters the nucleus of the host cell,
and uses the DNA polymerase (of the host cell) to create more
copies of itself. The virus also uses its host cell to translate viral
mRNA into viral proteins.
In RNA viruses, the viral RNA stays in the cytoplasm and is used by
the host’s ribosome to create viral RNA polymerase protein. These
Classification will help replicate the viral genome -> so more viruses can be
created.
Viral classification can be based on:
RNA polymerases are more likely to
1. Difference in genome (DNA or RNA)
make errors than DNA polymerases
In case of DNA viruses, there is a subdivision in double-stranded
(due to lack of proofreading ability). This is
and single-stranded DNA; linear and circular DNA.
why mutations in RNA viruses occur
In case of RNA viruses, they could be: more frequently than in DNA viruses.
● (+)RNA (ssRNA) = RNA virus that has the same form as mRNA.
● (-)RNA (ssRNA) = RNA virus that is complementary to mRNA
Common features of (+)ssRNA viruses:
● (+/-)RNA (dsRNA) = RNA virus that has double-stranded RNA
➢ They have a + polarity, so they can act directly as mRNA, and
● (+)RNA (ssRNA) via DNA (dsDNA) = RNA virus whose replication
therefore, they can be directly translated into viral proteins.
goes from RNA to DNA, instead of the other way around =
➢ This means that naked genomic RNA is directly infectious
retrovirus
and does not need anything else.
Common features of (-)ssRNA viruses:
➢ They are the complementary strand of mRNA, and therefore,
not directly infectious.
➢ They need to carry their own RNA-dependent
RNA-polymerase in their virion, since we humans do not
have this.
➢ So far, all (-)RNA viruses that are known have an envelope.
Common features of dsDNA viruses:
➢ Before they can translate into viral proteins, they first follow
the central dogma of biology (DNA -> mRNA -> proteins).
➢ They either use host proteins or encode their own to
transcribe the DNA into RNA.
➢ The ds-DNA viruses genomes often encode for more viral
genes to manipulate host cells and defences -> more
complex strategies and various evasion strategies.
2. Presence of an envelope
The larger the genome, the more information (genes) the virus
can carry, the larger the capsid or envelope structure is to contain
the genome.
, The way viruses can interact with the host and different types of
host cells is defined as host/tissue tropism, which is determined
by VAPs or glycoproteins (in case of enveloped viruses).
Host/tissue tropism refers to how various viruses/pathogens have
evolved to preferentially target particular host organisms, tissues,
or cell types inside those species.
e.g. the enveloped HIV virus has VAP gp120 that
binds to CD4 receptors on T-helper cells, dendritic
cells, or macrophages, which means that HIV can
attach and invade T-helper cells.
2. Penetration/entry
Interactions between multiple VAPs and cellular receptors initiate
the internalization of the virus into the cell. The mechanism of
internalization depends on the virion structure and cell type.
Viral replication
Most naked viruses enter the cell by receptor-mediated
For viral replication, the general goal is to replicate itself inside a
endocytosis or by viropexis:
suitable host cell. This is done in an orderly series of events during
● Endocytosis is a normal process used by the cell for the
infection, however, every virus has its own replication mechanism.
uptake of receptor-bound molecules, such as hormones,
Lytic & lysogenic cycles low-density proteins, and transferrin.
A virus undergoes lytic and lysogenic cycles to reproduce. ● Viropexis is the way most viruses enter the cell.
->do not have an envelope, so don’t have glycoproteins ->
The lytic cycle is relatively more common, wherein a virus infects a
Hydrophobic structures (capsid proteins) may be exposed
host cell, uses its metabolism to multiply, and then destroys the
after viral binding -> allow the virus/viral genome to slip
cell completely.
through (direct penetration) the membrane (also called
The lysogenic cycle depends largely upon the lytic cycle. Here, the
pinocytosis).
virus integrates its genetic information with that of the host
Enveloped viruses mostly enter the host cell through fusion
(instead of the virus destroying the host DNA) and then becomes
(budding): they fuse their membranes with cellular membranes to
dormant, letting the host cell multiply and continue its normal
deliver the nucleocapsid or genome directly into the cytoplasm
activities. The viral DNA is carried from generation to generation.
(neutral pH).
At some point, the virus is triggered, and it thereafter goes on to
the lytic cycle: it multiplies and ultimately, destroys the host cell. When there is a low pH, the virus has to fuse with an endosome
(endocytosis).
There are some general rules (/steps) for viral replication. -> only
have to remember the few exceptions.
1. Recognition of the target cell + attachment
Viruses lack the capacity to make energy or substrate, they
cannot make their own proteins and cannot replicate their
genome independently of the host cell. This is all due the fact that
3. Uncoating
they do not have the organelles required for these things.
Once internalized, the nucleocapsid must be delivered to the site
So for replication to happen, viruses first need to encounter a of replication within the cell (cytosol for RNA, nucleus for DNA), so
susceptible host or tissue (living cell). the capsid and/or envelope must be removed.
Then, the virus has to attach to the host. The viral attachment The uncoating process may be initiated by attachment to the
structure may be part of the capsid or a protein that extends from receptor or promoted by the acidic environment of proteases
the capsid. Specific glycoproteins are the VAPs of enveloped found in an endosome or lysosome. The released proteins in this
viruses, which bind to receptors on the target (host) cell. stage are non-structural, enzymes, and nucleic acid binding
proteins.
, 4. Macromolecular synthesis 6. Budding of enveloped viruses
Once the genome floats freely inside the cell, the genome must Budding is only for enveloped viruses!
direct the synthesis of viral mRNA and structural proteins. It also The glycoproteins stick into the cytoplasmic membrane of the
must generate identical copies of itself. host cell. The viral proteins align against the inner side
The genome is useless unless it can be transcribed into functional (cytoplasmic membrane) of the host clel, where they
mRNAs capable of binding to ribosomes and being translated ultimately assemble.
into proteins. The means by which each virus accomplishes these These viral particles are budded off from the membrane of the
steps depends on the structure of the genome: host cell, and in that way they ‘take’ the membrane of the host
● (+)ssRNA is the same form as mRNA so this can directly bind cell with them. This piece of membrane surrounds the
ribosomes and translate into proteins :) nucleocapsid, thereby forming the envelope.
● (-)ssRNA needs RNA polymerase (from the virus itself) for The budding of enveloped viruses happens without killing the host
the transcription of the genome into mRNA (+ssRNA), which cell. This survival of the host allows continual production and
can then translate into proteins release of viruses.
● dsDNA is transcribed into (+)ssRNA (mRNA) like always
● ssDNA first needs to be converted into dsDNA and then, as
7. Exit/release of virus
normal, is transcribed into (+)ssRNA (mRNA).
The three mechanisms of release are:
● (+)ssRNA (retro) become dsDNA (retro=replication from RNA
1. lysis of the cell (breaking down of the
to DNA), then it is transcribed into (+ss)RNA (mRNA) as
membrane of a cell by viral mechanisms)
normal. 2. exocytosis (vesicles containing the virus are
secreted out of the infected cell)
To make it easier: 3. budding from the plasma membrane
(cell membrane is budded off and taken by the virus)
- know that dsDNA -> mRNA -> proteins
- remember (+)ssRNA = mRNA Some enveloped viruses are released through lysis of the cell or
through exocytosis.
Naked viruses are mainly released through lysis.
So enveloped viruses enter the bacterial cell by budding or
endocytosis and they leave the cell by budding of, exocytosis, or
5. Assembly of virus
lysis of the cell.
Reproduction of viruses occurs by assembly of individual
Naked viruses enter the bacterial cell by endocytosis or viropexis
components rather than by binary fission (like bacteria).
and leave the cell through lysis.
The assembly process begins when the necessary pieces are
synthesized and the concentration of structural proteins in the cell
is sufficient to drive the process thermodynamically.
Each part of the virion has recognition structures that allow the
virus to form the appropriate protein-protein, protein-nucleic acid,
and (for enveloped viruses) protein-membrane interactions
needed to assemble into the final structure.
The assembly process may be facilitated by scaffolding proteins
or other proteins.
The site and mechanism of virion assembly in the cell depends on
where genome replication occurs and whether the final structure
is a naked virus or an enveloped virus.
● Naked viruses may be assembled as empty
structures/shells (procapsids) to be filled with the genome,
or they may be assembled around the genome.
● For enveloped viruses, newly synthesized and processed viral
glycoproteins are delivered to cellular membranes by Viral replication cycle
vesicular transport. A single round of the viral replication cycle can be separated into
several phases:
1. Early phase: step 1-3 (from recognizing an appropriate target cell to the
release of its genome into the cytoplasm (uncoating))
2. Late phase: step 4 (begins with the start of genome replication and viral
macromolecular synthesis and proceeds through viral assembly and release)
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