Samenvatting
Summary infectious diseases (NWI-BB097)
- Instelling
- Radboud Universiteit Nijmegen (RU)
Uitgebreide samenvatting van de stof voor het vak infectious diseases.
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Voorbeeld van de inhoud
Summary infectious diseases,Chapter 1 viruses: background and
diagnostic tests
Infectious diseases infect their hosts and need them for nutrients and multiplication. Infectious
diseases life cycle roughly looks as follows:
• Infection → host invasion → immune evasion → multiplication and shedding → spread
• A lot of disease symptoms help the transmission of the disease (e.g. fluid filled bumps of
herpes simplex)
There are different routes of transmission known for infectious diseases, the most important ones of
which are:
• Horizontal: adult-adult
• Vertical: adult-next generation → mother to child
• zoonotic diseases are diseases which reservoir of replication are animals → zoonoses
Viruses and their replication
Viruses where first identified by the fact that diseased tobacco plants’ that were filtered could still
infect other tobacco plants → conclusion that the infectious agent was smaller than a bacterium,
then it was regarded as ‘a living fluid’. Later, it was also observed that the blood of animals with Foot
and Mouth disease was still infectious after it passed through a Chamberland filter and that the host
was necessary for replication.
A virus is a small, obligatory intracellular, infectious agent
• replication only in the host, not in medium → host makes nutrients
for multiplication and has multiplication machinery
− full host dependence for energy metabolism, lipid biogenesis and protein synthesis
• no growth or division: they are an de novo assembly of pre-formed building blocks
• protein coat and their own genetic material → no complete translation system or membrane
apparatus
• not all viruses cause disease
• all organisms are infected by a certain set of viruses
• viruses are everywhere
A virus is comprised of different components → these components, their composition and
arrangement differs for each type of virus
• Virion: complete virus particle
• Capsid: protein shell that surrounds the viral nucleic acids → this capsid
may be bound directly to the nucleic acids, but this is not always the case
− contains proteins that mediate viral entry of the cells
• Nucleocapsid: is the term used to refer to the capsid including the nucleic
acid
• Envelope: a lipid coat that surrounds the capsid
− serves a role in immune evasion as B cells make less potent antibodies to lipids than
to proteins
The replication of viruses is comparable for each virus type, however there are certain differences.
Below is given a general scheme of the viral replication cycle.
1. first the virus infects the host
, 2. Then it attaches to cells of a certain tissue that bears
receptors to which the virus specifically attaches
3. Then the virus penetrates into the cell → envelopes lost
during entry
4. Uncoating of the virus when in the endosomes → low pH
induces a conformational change in the nucleocapsid that
causes uncoating and release of the genetic material into the
cell cytoplasm → capsid shed
5. Replication of the viral genetic material, as well as translation
6. Assembly of newly formed capsids around the multiplied
genetic material
7. Release of newly formed viruses after budding of the capsid
into the cell membrane may form an envelope
Viral infection dissemination by:
• killing of infected cells by CTL-mediated lysis
• prevention of viral infection by anti-virion antibodies, as well as induced antiviral state of
cells surrounding infected cells
→ more of this in a later chapter
Classification of viruses
Viruses are very diverse, as they can differ in size, shape, components, nucleic acid type, sequence
and much more. A classification of viruses has been developed by mister
Baltimore known as the Baltimore classification.
• This classification is based on the genome types of the viruses, as
this is not that diverse → for as far as we know there are only seven
genome types
− dsDNA viruses: deposit both (-)DNA and (+)DNA strand →
translated into mRNA by RNA polymerase
− (+) strand ssRNA viruses: (+)RNA is sense RNA that can be
directly translated by the host ribosomes → RNA dependent
RNA polymerase encoded for RNA replication
− (-) strand ssRNA viruses: (-)RNA is anti-sense RNA that cannot be directly translated
by the host ribosomes → RNA dependent RNA polymerase (RDRP) accompanied in
virion
− retroviruses: (+)RNA that is reverse transcribed by reverse transcriptase (RT) into
(-)DNA → transcribed in more (+)RNA: translated by ribosomes
− gapped dsDNA viruses
− dsRNA viruses: both (-) and (+)RNA wrapped around each other
, • Assumes that all viruses make mRNA that can be read by the host ribosomes
• Note that viruses of the same taxa share their replication mechanism
• Viruses of the same family does by no means mean that they cause similar disease and have
the same transmission routes
• Family of a virus does not explain its tissue tropism or pathogenesis
Physical classification of viruses is applied overarching the Baltimore classification → until very
recently this classification required isolation of the virion
• Nature (and sequence) of nucleic acid in virion
• symmetry of the capsid
• presence or absence of an envelope
• Dimensions of virion and capsid
Virus detection and diagnostics
There are various methods to detect viral infections and quantify the viral load. These methods can
be divided in direct and indirect methods.
• With direct detection one detects real (parts of) the virus, this can be for example:
− the whole infectious particle
− structural components: viral proteins, genetic material
− their products e.g. toxins → although most relevant for bacteria and fungi
• With indirect detection one detects the consequences of the virus so to speak
− IgM; more or less 3 days after infection
− seroconversion to IgG; more or less 10 days after infection
Amongst the direct detection methods are:
• Detection of (infectious) viral particles via
− Culture based methods
o cytopathic effect (CPE): observe structural changes in monolayer of
susceptible cells as an effect of an applied patient/research sample
▪ Confirmation of the presence of a virus
▪ Sometimes observed CPE is characteristic for a certain virus (e.g.
‘owls eye’ for CMV) → allows for identification
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