INHOUDSOPGAVE
H1: introduction to virology: what are viruses? where do they originate? – classification of viruses –
the virology toolbox – virus structures – replication cycles – virus evolution .................................... 9
what are viruses? ............................................................................................................................. 9
astonishing number of viruses on earth ............................................................................................. 9
all viruses are obligatory parasites .................................................................................................... 9
virus replication ..............................................................................................................................10
viruses have high genome evolution rates .........................................................................................11
are viruses dead or alive? ................................................................................................................11
origin of viruses? .............................................................................................................................12
a typical virus genome .....................................................................................................................12
a chimeric origin of viruses ..............................................................................................................12
five hallmark viral replication genes .................................................................................................13
cellular ancestry of capsids .............................................................................................................13
a brief history of virology ..................................................................................................................13
koch’s postulates to affirm the causes of infectious diseases........................................................ 14
21st century revised version of koch’s postulates .......................................................................... 14
virus classification ..........................................................................................................................14
definitions/rules underlying the Baltimore system......................................................................... 15
viruses with dna genomes ............................................................................................................ 16
viruses with rna genomes ............................................................................................................ 17
ambisense rna genomes .............................................................................................................. 19
summary of 7 genome classes according to baltimore .................................................................. 20
what information is encoded by the viral genome? ............................................................................21
what information is not encoded by the viral genome? ......................................................................21
summary (examen!) ........................................................................................................................21
the virology toolbox .........................................................................................................................21
virus diagnostic methods ............................................................................................................. 21
a typical virus genome .....................................................................................................................27
virus particles are made up from structural proteins ..................................................................... 27
virus structural ............................................................................................................................ 28
virus particles are metastable ...................................................................................................... 28
the viral replication cycle .................................................................................................................34
steps in virus replication .............................................................................................................. 34
step 1: binding to cell receptor ..................................................................................................... 34
step 2: entry and uncoating .......................................................................................................... 36
genome transcription & translation (step 3 and 5) .............................................................................41
some definitions.......................................................................................................................... 41
modifications to the central dogma of molecular biology............................................................... 41
1
, viral mrna’s are capped at the 5’ end ............................................................................................ 44
viral mrna’s are polyadenylated at the 3’ end (poly-a-tale) ............................................................. 45
monocistronic & polycistronic mrna’s .......................................................................................... 46
post-translational modifications .................................................................................................. 47
summary: genome transcription of eukaryotic viruses & transcriptases ......................................... 47
genome replication (step 4) .............................................................................................................49
why genome replication? ............................................................................................................. 49
locations of virus genome replication in eukaryotic cells ............................................................... 50
initiation of genome replication .................................................................................................... 50
dna strand displacement replication ............................................................................................ 51
key enzymes in rna virus genome replication ................................................................................ 51
reverse transcription ................................................................................................................... 52
genome replication according the baltimore classification ............................................................ 53
assembly & exit ...............................................................................................................................53
the structure of a virion determines how it is formed ..................................................................... 53
three strategies for making sub-assemblies .................................................................................. 55
genome packaging ...................................................................................................................... 56
virion exit from the cell ................................................................................................................. 58
virus evolution.................................................................................................................................61
phylogenetics.............................................................................................................................. 61
virus evolution and main drivers of evolution ................................................................................ 61
virus evolution ............................................................................................................................. 66
constraints on virus evolution ...................................................................................................... 67
next series of lectures .....................................................................................................................67
in summary .....................................................................................................................................67
H2: respiratory viral infections ..................................................................................................... 68
the importance of respiratory infections ...........................................................................................68
respiratory tract ..............................................................................................................................68
bronchitis/bronchiolitis ............................................................................................................... 68
pneumonia ................................................................................................................................. 69
other respiratory conditions ......................................................................................................... 69
viral cause of rti ...............................................................................................................................69
general overview .............................................................................................................................70
respiratory virus transmission ..........................................................................................................70
aerosol deposition....................................................................................................................... 71
respiratory virus seasonality ............................................................................................................71
humidity/temperature ................................................................................................................. 72
respiratory syncytial virus ................................................................................................................73
pneumoviridae ............................................................................................................................ 73
epidemiology .............................................................................................................................. 74
treatment .................................................................................................................................... 74
prevention................................................................................................................................... 75
human metapneumovirus ...............................................................................................................75
2
, pneumoviridae ............................................................................................................................ 75
adenovirus ......................................................................................................................................75
adenoviridae ............................................................................................................................... 75
epidemiology .............................................................................................................................. 77
vaccines ..................................................................................................................................... 77
parainfluenzavirus...........................................................................................................................77
paramyxoviridae .......................................................................................................................... 77
epidemiology .............................................................................................................................. 78
treatment and prevention ............................................................................................................ 79
rhinovirus – respiratory enterovirus ..................................................................................................79
picornaviridae ............................................................................................................................. 79
epidemiology .............................................................................................................................. 80
treatment & prevention ................................................................................................................ 81
non-rhinovirus enteroviruses ...........................................................................................................81
taxonomy .................................................................................................................................... 81
EnteroVirus D68 .......................................................................................................................... 81
impact of covid-19 NPI on epidemiology of respiratory viruses ...........................................................81
respiratory syncytial virus ................................................................................................................84
H3: herpesviruses ....................................................................................................................... 85
main characteristics .......................................................................................................................85
classification ..................................................................................................................................85
subfamilies ................................................................................................................................. 85
human herpesviruses .................................................................................................................. 86
viral structure..................................................................................................................................87
genome ..........................................................................................................................................87
hsv-1 – human herpesvirus 1 (hhv-1) ............................................................................................ 87
replication cycle .............................................................................................................................88
entry ........................................................................................................................................... 89
nuclear pore transport ................................................................................................................. 90
assembly & exit ........................................................................................................................... 90
hhv-1 ..............................................................................................................................................91
herpes simplex virus type 1 – HSV-1 – HHV1 ................................................................................. 91
hhv-2 ..............................................................................................................................................92
herpes simplex virus type 2 – HSV-2 – HHV2 ................................................................................. 92
HHV-3 ............................................................................................................................................93
varicella zoster virus – VZV ........................................................................................................... 93
hhv-5 ..............................................................................................................................................94
cytomegalovirus – cmv ................................................................................................................ 94
hhv-4 ..............................................................................................................................................95
epstein barr virus – ebv – hhv-4 ..................................................................................................... 95
hhv6A/B hhv7 ..................................................................................................................................96
3
, rash causing viruses – viral exanthema ......................................................................................... 96
hhv-8 ..............................................................................................................................................97
kaposi sarcoma associated herpes virus (kshv) – HHV-8 ............................................................... 97
H1: emerging & re-emerging viruses: emerging viruses – arboviruses – HIV .................................... 98
who pathogen priority list.................................................................................................................98
major drivers of virus emergence & spread .......................................................................................98
1. demographic changes & urbanisation ................................................................................ 98
2. globalisation of travel & trade ............................................................................................ 98
3. intense agriculture & livestock ........................................................................................... 98
4. bushmeat & animal trade .................................................................................................. 98
5. climate change ................................................................................................................. 98
6. biodiversity loss & habitat destruction (also caused by 3, 4 and 5) ....................................... 98
7. intrinsic viral property of rapid genome evolution................................................................ 99
obligate intracellular parasites with small genomes & high mutation rates .........................................99
zoonotic origin ................................................................................................................................99
major agents of viral hemorrhagic fevers (VHFs).............................................................................. 100
ebola virus ................................................................................................................................ 100
marburg virus: another filovirus causing sporadic outbreaks in humans ....................................... 109
arboviruses ................................................................................................................................... 112
global map of emerging infections in humans since 1998 ............................................................ 112
arboviruses cycle between insects & vertebrate hosts ................................................................ 112
arboviruses in a highly connected, urbanising & warming world ................................................... 112
clinically indistinguishable febrile syndrome & co-circulation ...................................................... 112
classification ............................................................................................................................ 113
risk of aedes albopictus-borne chikungunya virus in europe ........................................................ 113
environmental suitability for dengue occurrence worldwide ........................................................ 113
epidemic drivers ........................................................................................................................ 114
dengue virus.............................................................................................................................. 114
zika virus ................................................................................................................................... 122
other (re)emerging flaviviruses ................................................................................................... 125
(re)emerging neutotropic flaviviruses.......................................................................................... 128
chikungunya ............................................................................................................................. 129
oropouche ................................................................................................................................ 134
why is there a need to diagnose? ................................................................................................ 136
summary ...................................................................................................................................... 139
h2: the human immunodeficiency virus (hiv) ............................................................................... 140
baltimore classification ................................................................................................................. 140
hiv – more than just one virus ......................................................................................................... 140
zoonotic origin of hiv-1 groups m, n, o and p ............................................................................... 140
zoonotic origin of hiv-2 ............................................................................................................... 140
hiv particle .................................................................................................................................... 141
hiv genomic structure .................................................................................................................... 141
4
H1: introduction to virology: what are viruses? where do they originate? – classification of viruses –
the virology toolbox – virus structures – replication cycles – virus evolution .................................... 9
what are viruses? ............................................................................................................................. 9
astonishing number of viruses on earth ............................................................................................. 9
all viruses are obligatory parasites .................................................................................................... 9
virus replication ..............................................................................................................................10
viruses have high genome evolution rates .........................................................................................11
are viruses dead or alive? ................................................................................................................11
origin of viruses? .............................................................................................................................12
a typical virus genome .....................................................................................................................12
a chimeric origin of viruses ..............................................................................................................12
five hallmark viral replication genes .................................................................................................13
cellular ancestry of capsids .............................................................................................................13
a brief history of virology ..................................................................................................................13
koch’s postulates to affirm the causes of infectious diseases........................................................ 14
21st century revised version of koch’s postulates .......................................................................... 14
virus classification ..........................................................................................................................14
definitions/rules underlying the Baltimore system......................................................................... 15
viruses with dna genomes ............................................................................................................ 16
viruses with rna genomes ............................................................................................................ 17
ambisense rna genomes .............................................................................................................. 19
summary of 7 genome classes according to baltimore .................................................................. 20
what information is encoded by the viral genome? ............................................................................21
what information is not encoded by the viral genome? ......................................................................21
summary (examen!) ........................................................................................................................21
the virology toolbox .........................................................................................................................21
virus diagnostic methods ............................................................................................................. 21
a typical virus genome .....................................................................................................................27
virus particles are made up from structural proteins ..................................................................... 27
virus structural ............................................................................................................................ 28
virus particles are metastable ...................................................................................................... 28
the viral replication cycle .................................................................................................................34
steps in virus replication .............................................................................................................. 34
step 1: binding to cell receptor ..................................................................................................... 34
step 2: entry and uncoating .......................................................................................................... 36
genome transcription & translation (step 3 and 5) .............................................................................41
some definitions.......................................................................................................................... 41
modifications to the central dogma of molecular biology............................................................... 41
1
, viral mrna’s are capped at the 5’ end ............................................................................................ 44
viral mrna’s are polyadenylated at the 3’ end (poly-a-tale) ............................................................. 45
monocistronic & polycistronic mrna’s .......................................................................................... 46
post-translational modifications .................................................................................................. 47
summary: genome transcription of eukaryotic viruses & transcriptases ......................................... 47
genome replication (step 4) .............................................................................................................49
why genome replication? ............................................................................................................. 49
locations of virus genome replication in eukaryotic cells ............................................................... 50
initiation of genome replication .................................................................................................... 50
dna strand displacement replication ............................................................................................ 51
key enzymes in rna virus genome replication ................................................................................ 51
reverse transcription ................................................................................................................... 52
genome replication according the baltimore classification ............................................................ 53
assembly & exit ...............................................................................................................................53
the structure of a virion determines how it is formed ..................................................................... 53
three strategies for making sub-assemblies .................................................................................. 55
genome packaging ...................................................................................................................... 56
virion exit from the cell ................................................................................................................. 58
virus evolution.................................................................................................................................61
phylogenetics.............................................................................................................................. 61
virus evolution and main drivers of evolution ................................................................................ 61
virus evolution ............................................................................................................................. 66
constraints on virus evolution ...................................................................................................... 67
next series of lectures .....................................................................................................................67
in summary .....................................................................................................................................67
H2: respiratory viral infections ..................................................................................................... 68
the importance of respiratory infections ...........................................................................................68
respiratory tract ..............................................................................................................................68
bronchitis/bronchiolitis ............................................................................................................... 68
pneumonia ................................................................................................................................. 69
other respiratory conditions ......................................................................................................... 69
viral cause of rti ...............................................................................................................................69
general overview .............................................................................................................................70
respiratory virus transmission ..........................................................................................................70
aerosol deposition....................................................................................................................... 71
respiratory virus seasonality ............................................................................................................71
humidity/temperature ................................................................................................................. 72
respiratory syncytial virus ................................................................................................................73
pneumoviridae ............................................................................................................................ 73
epidemiology .............................................................................................................................. 74
treatment .................................................................................................................................... 74
prevention................................................................................................................................... 75
human metapneumovirus ...............................................................................................................75
2
, pneumoviridae ............................................................................................................................ 75
adenovirus ......................................................................................................................................75
adenoviridae ............................................................................................................................... 75
epidemiology .............................................................................................................................. 77
vaccines ..................................................................................................................................... 77
parainfluenzavirus...........................................................................................................................77
paramyxoviridae .......................................................................................................................... 77
epidemiology .............................................................................................................................. 78
treatment and prevention ............................................................................................................ 79
rhinovirus – respiratory enterovirus ..................................................................................................79
picornaviridae ............................................................................................................................. 79
epidemiology .............................................................................................................................. 80
treatment & prevention ................................................................................................................ 81
non-rhinovirus enteroviruses ...........................................................................................................81
taxonomy .................................................................................................................................... 81
EnteroVirus D68 .......................................................................................................................... 81
impact of covid-19 NPI on epidemiology of respiratory viruses ...........................................................81
respiratory syncytial virus ................................................................................................................84
H3: herpesviruses ....................................................................................................................... 85
main characteristics .......................................................................................................................85
classification ..................................................................................................................................85
subfamilies ................................................................................................................................. 85
human herpesviruses .................................................................................................................. 86
viral structure..................................................................................................................................87
genome ..........................................................................................................................................87
hsv-1 – human herpesvirus 1 (hhv-1) ............................................................................................ 87
replication cycle .............................................................................................................................88
entry ........................................................................................................................................... 89
nuclear pore transport ................................................................................................................. 90
assembly & exit ........................................................................................................................... 90
hhv-1 ..............................................................................................................................................91
herpes simplex virus type 1 – HSV-1 – HHV1 ................................................................................. 91
hhv-2 ..............................................................................................................................................92
herpes simplex virus type 2 – HSV-2 – HHV2 ................................................................................. 92
HHV-3 ............................................................................................................................................93
varicella zoster virus – VZV ........................................................................................................... 93
hhv-5 ..............................................................................................................................................94
cytomegalovirus – cmv ................................................................................................................ 94
hhv-4 ..............................................................................................................................................95
epstein barr virus – ebv – hhv-4 ..................................................................................................... 95
hhv6A/B hhv7 ..................................................................................................................................96
3
, rash causing viruses – viral exanthema ......................................................................................... 96
hhv-8 ..............................................................................................................................................97
kaposi sarcoma associated herpes virus (kshv) – HHV-8 ............................................................... 97
H1: emerging & re-emerging viruses: emerging viruses – arboviruses – HIV .................................... 98
who pathogen priority list.................................................................................................................98
major drivers of virus emergence & spread .......................................................................................98
1. demographic changes & urbanisation ................................................................................ 98
2. globalisation of travel & trade ............................................................................................ 98
3. intense agriculture & livestock ........................................................................................... 98
4. bushmeat & animal trade .................................................................................................. 98
5. climate change ................................................................................................................. 98
6. biodiversity loss & habitat destruction (also caused by 3, 4 and 5) ....................................... 98
7. intrinsic viral property of rapid genome evolution................................................................ 99
obligate intracellular parasites with small genomes & high mutation rates .........................................99
zoonotic origin ................................................................................................................................99
major agents of viral hemorrhagic fevers (VHFs).............................................................................. 100
ebola virus ................................................................................................................................ 100
marburg virus: another filovirus causing sporadic outbreaks in humans ....................................... 109
arboviruses ................................................................................................................................... 112
global map of emerging infections in humans since 1998 ............................................................ 112
arboviruses cycle between insects & vertebrate hosts ................................................................ 112
arboviruses in a highly connected, urbanising & warming world ................................................... 112
clinically indistinguishable febrile syndrome & co-circulation ...................................................... 112
classification ............................................................................................................................ 113
risk of aedes albopictus-borne chikungunya virus in europe ........................................................ 113
environmental suitability for dengue occurrence worldwide ........................................................ 113
epidemic drivers ........................................................................................................................ 114
dengue virus.............................................................................................................................. 114
zika virus ................................................................................................................................... 122
other (re)emerging flaviviruses ................................................................................................... 125
(re)emerging neutotropic flaviviruses.......................................................................................... 128
chikungunya ............................................................................................................................. 129
oropouche ................................................................................................................................ 134
why is there a need to diagnose? ................................................................................................ 136
summary ...................................................................................................................................... 139
h2: the human immunodeficiency virus (hiv) ............................................................................... 140
baltimore classification ................................................................................................................. 140
hiv – more than just one virus ......................................................................................................... 140
zoonotic origin of hiv-1 groups m, n, o and p ............................................................................... 140
zoonotic origin of hiv-2 ............................................................................................................... 140
hiv particle .................................................................................................................................... 141
hiv genomic structure .................................................................................................................... 141
4
