2025-2026 Pathogenesis
PATHOGENESIS AND CLINICAL
ASPECTS OF TROPICAL INFECTIOUS
DISEASES
HUMAN IMMUNODEFICIENCY VIRUS (HIV/AIDS)
GENERAL CHARACTERISTICS OF HIV
• HIV belongs to group VI of the Baltimore classification: ss(+)RNA
o Diploid ss(+)RNA genome with dsDNA intermediate
o Family: Retroviridae
o Genus: Lentivirus
• It has virulence factors: reverse transcriptase and integrase for integration of its genetic
material into the host genome = once infected, infected for life
ORIGIN OF HIV
• It has a zoonotic origin, but is now transmitted anthroponotically
• How did they identify its zoonotic origin? First, faeces from non-human primates were collected
in tropical areas which were tested on the presence of Ab against HIV-related viruses. On the Ab-
positive specimens, they looked for viral RNA using PCR. At last, they sequenced mtDNA to
determine the monkey species containing this virus in their feces.
• HIV originates from SIV (Simian immunodeficiency virus) Virus HIV-1
Group M N O P
o HIV-1 groups M, N, O and P is found in West-Central
Africa Source SIVcpz SIVcpz SIVgor SIVgor
§ M and N are derived from SIVcpz (SIV of Epidemic World No No No
chimpanzees) Virus HIV-2
§ P and O are derived from SIVgor (SIV of gorillas) Group A, B C, D, E, F, G, H
o HIV-2 is found in North-West Africa Source SIVsmm SIVsmm
§ Derived from SIVsmm (SIV of sootey mangabey Epidemic West Africa No
monkeys)
VIROLOGY
• HIV-1 group M is most prevalent and is the cause of the worldwide epidemic
• Based on the phylogenetic trees and where the samples were collected, they geographically
localized the initial jump from SIV to humans: for HIV-1 this could be traced back to the southern
part of Cameroon and Gabon (central/west Africa) and HIV-2 is traced back to West-Africa.
• How does this transmission happen? During capturing of monkeys (in West-Africa, monkeys are
hunted as bush meat and kept as pets) à we can get bitten/scratched making blood-blood
transmission possible
o They tested the prevalence of SIV in certain monkey species and the prevalence of
monkey species on bush meat markets = overlap in DRC (good opportunity for spill over)
1
, 2025-2026 Pathogenesis
• The initial jump of HIV-1, group M on men (SIV à HIV) happened around early 20th century (1920)
in Cameroon à this local outbreak exploded into a pandemic
o How did they know this? Analyzing genetic variation in viral subtypes = since a lot of
variation was seen in 1950’s-1960’s, the virus must have been around for a longer time
already
The global diversity of HIV-1 (subtypes A to K in
o During this time, there was colonization and a steep increase in size of cities/population
colors) together with the diversity of HIV-1 in the
which was a good moment for viral spread Democratic Republic of Congo (DRC, in black).
• In DRC we see the biggest variation in subtypes, suggesting DRC is the
epicenter of HIV
o Picture: global diversity of HIV-1 (subtypes A-K) (color) together with
the diversity of HIV-1 in DRC (black)
o In the Southern part of DRC there’s a mining region and a railway
from Kinshasa to Lubumbashi for work people à fast spread of HIV
o In the Northern part of DRC there’s transport via boat (over Congo
river), slowing down the spread of the virus
• In America, the first cases of HIV were detected in 1981, but since there was
some variation the introduction of HIV has probably been sooner VIROLOGY UNIT
• Thus: SIVcpz à patient zero with HIV-1 (1921) à 91.400.000 infections and 50.000.000 deaths
TRANSMISSION OF HIV
• Unprotected sexual intercourse with an infected partner
• Vertical transmission (mother to child)
o In utero
o During delivery
o Breastmilk
• Injection drug use
PROBABILITIES OF TRANSMISSION AND RELATIVE RISK
• Probability of HIV-1 transmission
o Male-to-male transmission (1/10-1/600)
o Male-to-female transmission (1/200-1/2000)
o Female-to-male transmission (1/200-1/10.000)
• People who are more at risk are transgender people, gay men, drug users (injection with needles)
and sex workers
• The risk of HIV transmission depends on blood viral load and stage of disease
o Higher viral load = higher chance of transmission
o This
Risk of HIV transmission higher viral
depends load occurs
on blood VL andduring
stage the acute phase (a lot of replication of virus and
of disease
unaware of infection) and the late stage/beginning of AIDS (our immune system can no
longer control infection)
VIROLOGY UNIT 2
,2025-2026 Pathogenesis
SEXUAL TRANSMISSION: MUCOSAL ROUTE
GENERAL
• This is the most important route of infection
• Transmission occurs through the epithelium of
o Vagina: multi-layered thus harder
o Cervix: single-layered thus easier
• Normally, this epithelium functions as a protective layer, but when it is damaged (mechanical
damage during sexual intercourse or inflammation because of another STI), the mucosal barrier
is disrupted. There can also be local inflammation and increased vascularization allowing HIV to
invade into the mucosa. Once HIV has crossed this barrier, it can interact with immune cells in
the mucosa (e.g. CD4 T-cells, macrophages, dendritic cells…). This causes local inflammation
by activating immune cells resulting in the production of cytokines (attracting more immune
cells/enhancing infection) or the dissemination of infected immune cells to lymph nodes
distributing the virus throughout the body.
• Thus, primary target = CD4 T-cells (mainly) as well as macrophages, dendritic cells…
TRANSMISSION ROUTE
• Sexual transmission from male to female/male
o HIV particles in ejaculate (seminal plasma)
o HIV-infected cells in ejaculate (leukocytospermia does not happen often but can occur
asymptomatically)
• Sexual transmission from female to male
o HIV particles in cervico-vaginal secretions
o HIV-infected cells in cervico-vaginal secretions
• Shedding is enhanced when there’s a co-infection with another STI = enhancing transmission
of HIV
o STI’s result in a thinned/damaged epithelium, providing direct access to target cells in
the submucosal tissue. The inflammation also attracts additional immune cells (target
cells) which allow direct systemic spread of the virus.
o Male: urethritis, genital ulcer disease, trichomonas vaginalis, cytomegalovirus…
o Female: bacterial vaginosis, HPV, Herpes, candida Thevulvovaginitis, Chlamydia,
male uro-genital tract
Gonorrhea…
• Male uro-genital tract:
o Outer foreskin = thick, cornified epithelial layer, good
protection
o Inner foreskin and epithelial lining of the urethra =
squamous epithelium, more susceptible to HIV
infection
o Circumcision (removing foreskin): removal of target
surface results in protection against HIV (glans penis
will cornify over time which gives protection against
infection) VI
3
, Female genital tract
2025-2026 Pathogenesis
• Female genital tract:
o The vagina/ectocervix is covered by multilayered
squamous epithelium which transforms into single
layered columnar epithelium in the endocervix =
squamo-columnar junction or ‘transformation
zone’
o This transformation zone is most vulnerable for HIV
infection
o Ectopic cervix: asymptomatic condition where the inner
The lining of
ano-rectal the endocervix extends
mucosa VI
in the ectocervix = this vulnerable tissue is now accessible for virus during sexual
intercourse
• Ano-rectal mucosa:
o Similar anatomical context as cervix
o There is a transition between multilayered and single
layered epithelium = ano-rectal junction
o This is very vulnerable; transmission probability
highest in MSM
GENETIC BOTTLENECK
VIROLO
• HIV is a very diverse virus; we will not get infected with 1 virus but multiple viruses (= quasi
species)
o Quasi species = genetic variants evolving together under high mutations rates (e.g. HIV)
• But not all virus variants are transmitted to the next person (most will not cross the mucosa or
result in a dead-end infection) à only when the virus is adapted to the new environment, it can
cause a local infection and spread systemically = genetic bottleneck over the epithelial lining
• Once a person is infected, the virus will diversify again, resulting in quasi species (the longer you
are infected, the more variants)
o It is not the most prevalent virus variant that is transmitted (in this case red), but usually
aGenetic
minorbottleneck
species during
better(sexual)
adaptedtransmission
for transmission (in this case green)
quasispecies quasispecies
• In this picture, we see that person 1 (green), infects another person with 1 HIV variant which
VIROLOGY UNIT
results in multiple new variants in the newly infected person 2 (blue) with smaller diversity than
donorGenetic bottleneck during (sexual) transmission
• 75% of patients are infected with a single virus, 25% of patients are infected with multiple
viruses (2-5)
o This transmission of multiple viruses is more common in homosexuals and infected
needle users (no epithelial barrier, diversity that is introduced is higher)
VIROLOGY UNIT
4
PATHOGENESIS AND CLINICAL
ASPECTS OF TROPICAL INFECTIOUS
DISEASES
HUMAN IMMUNODEFICIENCY VIRUS (HIV/AIDS)
GENERAL CHARACTERISTICS OF HIV
• HIV belongs to group VI of the Baltimore classification: ss(+)RNA
o Diploid ss(+)RNA genome with dsDNA intermediate
o Family: Retroviridae
o Genus: Lentivirus
• It has virulence factors: reverse transcriptase and integrase for integration of its genetic
material into the host genome = once infected, infected for life
ORIGIN OF HIV
• It has a zoonotic origin, but is now transmitted anthroponotically
• How did they identify its zoonotic origin? First, faeces from non-human primates were collected
in tropical areas which were tested on the presence of Ab against HIV-related viruses. On the Ab-
positive specimens, they looked for viral RNA using PCR. At last, they sequenced mtDNA to
determine the monkey species containing this virus in their feces.
• HIV originates from SIV (Simian immunodeficiency virus) Virus HIV-1
Group M N O P
o HIV-1 groups M, N, O and P is found in West-Central
Africa Source SIVcpz SIVcpz SIVgor SIVgor
§ M and N are derived from SIVcpz (SIV of Epidemic World No No No
chimpanzees) Virus HIV-2
§ P and O are derived from SIVgor (SIV of gorillas) Group A, B C, D, E, F, G, H
o HIV-2 is found in North-West Africa Source SIVsmm SIVsmm
§ Derived from SIVsmm (SIV of sootey mangabey Epidemic West Africa No
monkeys)
VIROLOGY
• HIV-1 group M is most prevalent and is the cause of the worldwide epidemic
• Based on the phylogenetic trees and where the samples were collected, they geographically
localized the initial jump from SIV to humans: for HIV-1 this could be traced back to the southern
part of Cameroon and Gabon (central/west Africa) and HIV-2 is traced back to West-Africa.
• How does this transmission happen? During capturing of monkeys (in West-Africa, monkeys are
hunted as bush meat and kept as pets) à we can get bitten/scratched making blood-blood
transmission possible
o They tested the prevalence of SIV in certain monkey species and the prevalence of
monkey species on bush meat markets = overlap in DRC (good opportunity for spill over)
1
, 2025-2026 Pathogenesis
• The initial jump of HIV-1, group M on men (SIV à HIV) happened around early 20th century (1920)
in Cameroon à this local outbreak exploded into a pandemic
o How did they know this? Analyzing genetic variation in viral subtypes = since a lot of
variation was seen in 1950’s-1960’s, the virus must have been around for a longer time
already
The global diversity of HIV-1 (subtypes A to K in
o During this time, there was colonization and a steep increase in size of cities/population
colors) together with the diversity of HIV-1 in the
which was a good moment for viral spread Democratic Republic of Congo (DRC, in black).
• In DRC we see the biggest variation in subtypes, suggesting DRC is the
epicenter of HIV
o Picture: global diversity of HIV-1 (subtypes A-K) (color) together with
the diversity of HIV-1 in DRC (black)
o In the Southern part of DRC there’s a mining region and a railway
from Kinshasa to Lubumbashi for work people à fast spread of HIV
o In the Northern part of DRC there’s transport via boat (over Congo
river), slowing down the spread of the virus
• In America, the first cases of HIV were detected in 1981, but since there was
some variation the introduction of HIV has probably been sooner VIROLOGY UNIT
• Thus: SIVcpz à patient zero with HIV-1 (1921) à 91.400.000 infections and 50.000.000 deaths
TRANSMISSION OF HIV
• Unprotected sexual intercourse with an infected partner
• Vertical transmission (mother to child)
o In utero
o During delivery
o Breastmilk
• Injection drug use
PROBABILITIES OF TRANSMISSION AND RELATIVE RISK
• Probability of HIV-1 transmission
o Male-to-male transmission (1/10-1/600)
o Male-to-female transmission (1/200-1/2000)
o Female-to-male transmission (1/200-1/10.000)
• People who are more at risk are transgender people, gay men, drug users (injection with needles)
and sex workers
• The risk of HIV transmission depends on blood viral load and stage of disease
o Higher viral load = higher chance of transmission
o This
Risk of HIV transmission higher viral
depends load occurs
on blood VL andduring
stage the acute phase (a lot of replication of virus and
of disease
unaware of infection) and the late stage/beginning of AIDS (our immune system can no
longer control infection)
VIROLOGY UNIT 2
,2025-2026 Pathogenesis
SEXUAL TRANSMISSION: MUCOSAL ROUTE
GENERAL
• This is the most important route of infection
• Transmission occurs through the epithelium of
o Vagina: multi-layered thus harder
o Cervix: single-layered thus easier
• Normally, this epithelium functions as a protective layer, but when it is damaged (mechanical
damage during sexual intercourse or inflammation because of another STI), the mucosal barrier
is disrupted. There can also be local inflammation and increased vascularization allowing HIV to
invade into the mucosa. Once HIV has crossed this barrier, it can interact with immune cells in
the mucosa (e.g. CD4 T-cells, macrophages, dendritic cells…). This causes local inflammation
by activating immune cells resulting in the production of cytokines (attracting more immune
cells/enhancing infection) or the dissemination of infected immune cells to lymph nodes
distributing the virus throughout the body.
• Thus, primary target = CD4 T-cells (mainly) as well as macrophages, dendritic cells…
TRANSMISSION ROUTE
• Sexual transmission from male to female/male
o HIV particles in ejaculate (seminal plasma)
o HIV-infected cells in ejaculate (leukocytospermia does not happen often but can occur
asymptomatically)
• Sexual transmission from female to male
o HIV particles in cervico-vaginal secretions
o HIV-infected cells in cervico-vaginal secretions
• Shedding is enhanced when there’s a co-infection with another STI = enhancing transmission
of HIV
o STI’s result in a thinned/damaged epithelium, providing direct access to target cells in
the submucosal tissue. The inflammation also attracts additional immune cells (target
cells) which allow direct systemic spread of the virus.
o Male: urethritis, genital ulcer disease, trichomonas vaginalis, cytomegalovirus…
o Female: bacterial vaginosis, HPV, Herpes, candida Thevulvovaginitis, Chlamydia,
male uro-genital tract
Gonorrhea…
• Male uro-genital tract:
o Outer foreskin = thick, cornified epithelial layer, good
protection
o Inner foreskin and epithelial lining of the urethra =
squamous epithelium, more susceptible to HIV
infection
o Circumcision (removing foreskin): removal of target
surface results in protection against HIV (glans penis
will cornify over time which gives protection against
infection) VI
3
, Female genital tract
2025-2026 Pathogenesis
• Female genital tract:
o The vagina/ectocervix is covered by multilayered
squamous epithelium which transforms into single
layered columnar epithelium in the endocervix =
squamo-columnar junction or ‘transformation
zone’
o This transformation zone is most vulnerable for HIV
infection
o Ectopic cervix: asymptomatic condition where the inner
The lining of
ano-rectal the endocervix extends
mucosa VI
in the ectocervix = this vulnerable tissue is now accessible for virus during sexual
intercourse
• Ano-rectal mucosa:
o Similar anatomical context as cervix
o There is a transition between multilayered and single
layered epithelium = ano-rectal junction
o This is very vulnerable; transmission probability
highest in MSM
GENETIC BOTTLENECK
VIROLO
• HIV is a very diverse virus; we will not get infected with 1 virus but multiple viruses (= quasi
species)
o Quasi species = genetic variants evolving together under high mutations rates (e.g. HIV)
• But not all virus variants are transmitted to the next person (most will not cross the mucosa or
result in a dead-end infection) à only when the virus is adapted to the new environment, it can
cause a local infection and spread systemically = genetic bottleneck over the epithelial lining
• Once a person is infected, the virus will diversify again, resulting in quasi species (the longer you
are infected, the more variants)
o It is not the most prevalent virus variant that is transmitted (in this case red), but usually
aGenetic
minorbottleneck
species during
better(sexual)
adaptedtransmission
for transmission (in this case green)
quasispecies quasispecies
• In this picture, we see that person 1 (green), infects another person with 1 HIV variant which
VIROLOGY UNIT
results in multiple new variants in the newly infected person 2 (blue) with smaller diversity than
donorGenetic bottleneck during (sexual) transmission
• 75% of patients are infected with a single virus, 25% of patients are infected with multiple
viruses (2-5)
o This transmission of multiple viruses is more common in homosexuals and infected
needle users (no epithelial barrier, diversity that is introduced is higher)
VIROLOGY UNIT
4
