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Volledige samenvatting Human Infectious Diseases
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- Wageningen University (WUR)
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[Meer zien]Voorbeeld 4 van de 45 pagina's
Voorbeeld 4 van de 45 pagina's
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Lecture 1 + 2: Introduction to VirologyExamples of viruses:
The Spanish flu (1918) death toll estimated at 50 million to 100 million worldwide,
caused by an H1N1 flu virus
Smallpox virus due to vaccination programs
Poliovirus eradication ongoing (> 2020)
Measles due to poor vaccination
Herpes simplex virus (HSV)
Human papillomavirus (HPV) genital warts mostly a benign virus, sexually
transmitted, some variants cause cancer
AIDS (HIV) Acquired ImmunoDeficiency Syndrome; virus breaks down the immune
system
Routes of virus transmission:
- Air influenza, SARS
- Water polio, diarrhea
- Contact HIV, ebola, herpes
- Food norovirus
- Vertical, germ line
- Mosquito vectors West Nile, Zika
Viruses are the smallest genetic entities and their presence often causes infectious disease.
Several characteristics of viruses:
1) Infectivity (=ability to enter host cells, to
multiply inside these cells, and to spread to
other cells)
2) Obligate, intracellular parasite need a cell
to live and to replicate
- No protein synthesizing machinery
- No energy producing machinery
3) Ability to survive in an extracellular state survive outside a living cell in an inert
state or via carrier
Virus = a piece of genetic information (RNA or DNA), protected by a protein coat and
sometimes a lipid membrane, which – upon infection of a living cell – will replicate to vast
amounts, coinciding with pathological effects on the host
LET OP! When a virus particle is enlarged 10 million times, it becomes as large as a soccer
ball.
1
,A virus is composed of:
- Nucleic acid RNA or DNA, ss or ds, segmented or non-segmented
- Protein shell assembled from smaller subunits: coat proteins
- Lipid membrane some viruses
Viral genomes are smaller than the genomes of cellular organisms. Viroids occur in plants
and their genomes are even smaller than viral genome lack essential information and can
only replicate with the help of host cell components or another virus.
Viruses are the only living entities on earth that may have a genome composed of RNA.
Hence, viruses can be divided into RNA and DNA.
What does a virus need?
Basically it only needs 2 genes. However, most complex viruses have 100 – 500 genes on 10 6
bp DNA genome.
First gene needed for replication.
Second gene is to capsule the virus, so
the virus can be recognised.
LET OP! RNA viruses mutate quicker
than viruses with a DNA genome. DNA polymerases have proofreading ability (to check) and
RNA polymerases don’t, so this takes more time this explains why most emerging viruses
that threaten human health are RNA viruses!
Among the single-stranded RNA viruses a further distinction can be made:
Most viruses are found in surface waters
- Oceans and fresh water lakes contain 5 – 150.106 viruses per ml
- Hosts: cyanobacteria and phytoplankton
- This corresponds with 1027 virus particles in total
- If you make a single string of these viruses they would cover a distance of 400.000
light years, spanning 16 times the milky way route
- Total organic mass corresponds with that of 75 million whales
2
,Functions of protein coat:
- Protection of the genetic material
- Recognition and penetration of the host cell with their surface they can recognize
receptors
- Escape from the immune / defense system (=minimizing antigenic determinants)
- Therefore: pursuing maximal symmetry (=in state of minimal energy)
- The viral coat is built up by smaller subunits; saving space on the genome
In certain viruses, the viral coat is surrounded by a lipid membrane = envelope
Lipid membrane contains proteins with complex sugar groups (glycans)
haemagglutinin and neuraminidase
Nearly all negative-stranded RNA viruses lack a clear protein coat, although a nucleoprotein
(N) protects the RNA. These viruses also have a viral envelope that surrounds and protects
the genome.
The surrounding protein coat and/or lipid envelope are needed for:
Forming the interface between the virus particle and the host cell surface
Needed for protection of the viral genome during the extracellular state of the virus
avoiding recognition and inactivation by the immune system of the host; achieved
by having a protein coat or lipid envelope with maximal symmetry and minimal
variation at the surface in this way, the number of antigenic determinants is kept
to a minimum (the more antigenic determinants, the higher the risk of recognition)
Structural proteins proteins that are present in the virus particle (=virion)
Non-structural proteins not present in the virus particle, but are produced after the virus
has entered the cell (are also encoded by the viral genome, but are not integrated in the
virions)
Architecture of viral coats
Viral coat proteins are small to achieve symmetry and avoid immune attack. Small genes also
increase the genetic stability; the risk of introducing undesired/lethal mutations is smaller
when the open reading frame is smaller limits the length of the coding sequence in the
genome and limits the space needed inside the virus particle to package the genome =
genetic space reduction.
Assembling a virus coat from smaller proteins, makes self-assembly possible.
3
, Rod-shaped viruses
Built up by a growing spiral in which all subunits are placed in equivalent positions relative to
each other viral genome is encapsidated as a spiral or helix. In this case, the size of the
rod-shaped particles can freely vary with the size of the genome to be encapsidated.
Spherical viruses
Even more symmetrical than rod-shaped viruses icosahedral symmetry. An icosahedron is
composed of 20 equilateral triangles. 3 coat proteins per triangle so 60 coat proteins can be
arranged in fully equivalent positions. In this way, the basic virion is formed, which can be
regarded as being composed of 12 pentamers of coat proteins; arranged around the 5-fold
symmetry axes.
More DNA or RNA? Triangulation will continue. 20 original triangles are subdivided into
smaller triangles.
LET OP! Even if all proteins are chemically identical, some will be in
an environment of 5 neighbours (pentamers) and other with 6
(hexamers). As the position between subunits is different for
pentameric and hexameric arrangements, the term quasi-
equivalency has been introduced for triangulated virus particles.
For T=3 the original triangles are divided
in 3 smaller triangles. There are 12
pentameric and 20 hexameric capsomers,
made from a total of 180 coat protein
molecules.
So, some rules:
• The number of pentamers is always 12
• The number of coat protein molecules divided by 60 gives the triangulation number
(T)
• The number of hexamers increases when T increases, and can be calculated as 10 *
(T-1)
Coat protein contains a large hydrophobic core eight-stranded anti-parallel ß-barrel. Part
of the isometric viruses are built up by a single type of coat protein, while others are built up
by 2 or even 3 types of coat proteins with different primary structures, but all sharing a
similar tertiary structure, the ß-barrel core.
4
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