Human infectious disease
Lecture 1 + 2
Protozoa, bacteria and viruses can cause human infectious diseases.
Virus examples are sars-cov-2, q-fever, influenza, malaria, zika and aids.
The poxvirus, HIV and sars-coV2 changed the course of history.
The Spanish flu in 1918 had 50 to 100 million worldwide deaths. It had the highest rate
among young, healthy adults. It was caused by an H1N1 flu virus.
Measles is often mild due to vaccination but can cause severe and long-term complications.
HPV is mostly a benign viruses. Is sexually transmitted and can cause cervical cancer (in
2009 vaccination programme)
HSV (Herpes simplex virus) is usually in the winter. Once you become infected, the virus will
stay with you. It is often reactivated by low immune system.
Chicken pox and shingles (gurdle herpes) is relatively benign. It is caused by varicella
zoster virus (a herpesvirus). Sometimes can be reactivated later in life. Asymmetrical, often
on one side of CNS.
HIV-infection can lead to AIDS: breaks down the immune system: opportunistic infections
such as by Candida which will lead to 100% mortality. It replicated in the CD4 helper cells
and kills them, so at the end you will have no CD4 helper cells left (no immune system left)
Foot-and-Mouth Disease Virus (FMDV) is an extremely picornavirus (Pico=small)
Virus infections often dictate population dynamics. In 2002 almost 50 percent of the seals
were killed by the measles.
Routes of virus transmission
- Air (influenza, SARS-CoV-2)
- Water (polio, diarrhoea)
- Contact (HIV, Ebola, herpes)
- Food (norovirus)
- Vertical (plant virus), germ line (via offspring)
- Mosquito vectors (West Nile, Chikungunya, Zika)
- Bats as virus reservois hosts: SARS, Hendra, Rabies
and Ebola
Viruses are the smallest genetic entities.
It is nothing more than genetic material (RNA or DNA genome)
that is protected by a protein coat (or sometimes a lipid
membrane). Once it enters a cell it releases the genetic
material, which will take over the cell. After this you get progeny virus (many virus particles) .
The presence of this often causes infectious disease.
Characteristics of viruses
1. Infectivity (property to penetrate a cell, to multiply within this cell and to leave the cell)
2. Obligate, intracellular parasite (cannot multiply without entering a living host cell)
, o No protein synthesizing machinery
o No energy producing machinery
3. Property to survive outside a living cell (in an inert state or via carrier)
Historical connotation
It all started in Wageningen with the tobacco mosaic virus by Adolf Mayer. Later it was
Martinus Beijerinck who found out that is was not a bacterial disease but a virus. This was
the first start of virology.
The “minimal” virus is 2 genes; one is the DNA/RNA polymerase and the other one is a
coat protein. With this you can build a virus.
Most viruses are found in surface waters.
Oceans and fresh water lakes contain 5-150 x 106 viruses per ml. Most of them are
cyanobacteria and phytoplankton. In total it is abound 1027 viruses particles in total.
There is a lot of biodiversity of viruses. The most common one is the bacteriophage.
Classification of viruses according to genome type (nucleic acid, replication strategy) can
been shown in a virosphere.
Functions of the protein coat
- Protection of the genetic material
- Recognition and penetration of the host cell (“host range”, “tissue tropism”)
- Escape from the immune / defense system (=minimizing antigenic determinants)
- Therefore: pursuing maximal symmetry (= minimal energy)
The viral coat is built up by smaller subunits for saving space on the genome, genetic
stability, possibility to self-assembly and structural requirement: assembly symmetric particle
from asymmetric proteins.
A spherical virion has 2-, 3- and 5-fold symmetry-axes and therefore reaches a minimal
energy state. This protect the nucleic acid. All spherical viruses have an icosahedrical
building plan, but some viruses are bigger than other -> further “triangulation”
T=1 icosahedral capsid protein: 12 pentameric capsomeres and 60 capsid proteins
T = 3 icosahedral capsid protein: 3x60=180 capsid proteins, 12 pentameric and 20
hexametric capsomeres
T=16 icosahedral capsid protein: 16x60=960 capsid proteins, 12 pentameric and 150
hexametric
T=25 icosahedral capsid protein: 25x60=1500 capsid proteins, 12 pentameric and 240
hexametric capsomeres
Triangulation number: smallest (T=1), bigger (T=16,25) and giant (T>1000) viruses. It
always had 12 pentamers, and the rest is hexamers (capsid proteins – 60) : 6 = hexamers.
E-module 1+2
Viruses are inert, (dead particles), as soon as they infect a host cell they might start to
multiply rapidly. This is paralleled by pathological effects (diseases).
, The sub microscopic dimension of viruses was the main reason why it took very long
before they were identified. Due to the development of electron microscopy and later DNA
technology a large number of viruses have been studied in detail. However, new viruses are
constantly being discovered. Viruses have a
large variety in morphological, functional and
structural characteristics.
Viral genome are smaller than genomes of
cellular organisms. Viroids occur in plants and
are even smaller than viral genomes.
Viruses are the only living entities on earth that
may have a genome composed of RNA.
Viruses and viroids also have a higher
mutation rate. In the figure can also been
seen that RNA viruses mutate quicker than
viruses with a DNA genome. This is because
DNA polymerase have a proofreading ability. RNA polymerase does not have this and
makes therefore more mistakes.
Viral DNA genomes may be linear or circular. All viral RNA genomes are linear, except the
genomes of viroids
Among the single-stranded RNA viruses also a distinction between positive and negative-
stranded RNA viruses can be made.
Virions (virus particles of positive-stranded RNA) carry an RNA genome that is translatable
by ribosomes into functional proteins. First the positive sense RNA viruses make a copy of
negative polarity (replication intermediate) which is then used as a template. It is of
“messenger-sense” and infectious when introduced to a suitable host cell. Poliovirus is an
example of this.
The negative-stranded RNA viruses cannot be translated by ribosomes, because the
antisense strand is encapsidated in the virions. Therefore, they carry RNA-dependent RNA
polymerase (RdRP). This promotes synthesis of the coding strand when the virus has
entered a cell. It will not initiate an infection and makes “reverse-genetics” systems
complicated. An example is the influenza virus.
The virus families end on viridae and names of the genera end on virus. Virus families,
genus and species names are all written in italics.
The viral coat can be protein or lipids, its also called the viral envelope. Nearly all negative-
stranded RNA viruses lack a clear protein coat, but a nucleoprotein (N) protects the RNA.
The viral-encoded proteins that are present in the virus particle (virion) are called structural
proteins. Non-structural proteins are not present in the virus particle but are produced after
the virus has entered a host cell. These have a crucial role in the virus replication cycle.
When the outermost layer of a virus particle is a lipid membrane the envelope contains one
or more glycoproteins. These are proteins with complex sugar groups (glycans) attached.
This is for example with influenza virus, which carries haemagglutinin (HA or H) and
neuraminidase (NA or N).
The outerlayer of a virus forms the interface between the virus particle and the host cell
surface. This has specific functions for recognizing and binding.
