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 The ability of an infectious agent to cause disease. A relative term in the sense
that it depends on the particular host that is infected and the state of that host as
well as the site of infection.
o Rabies and Ebola are highly virulent.
o Some viruses infect animals but are virulent only when the host immune
response is suppressed. Examples are certain herpes and hepatitis B virus
that become virulent when human hosts are treated with
immunosuppressant drugs after organ transplant.
General patterns of infection (Fig. 16.1)
 Acute
 Persistent
 Latent, reactivating
 Slow
Acute Infections
• Acute infections only detected by clinical symptoms.
• Can be acutely infected but assymptomatic…subclincal.
• Viruses usually produce large amounts of progeny
• Rapid onset of symptoms
• Rapid resolution of infection either by
– Immune clearance or
– Death
Defense against acute infections
Most acute infections are rapidly resolved
Limited by the intrinsic and innate immune responses
Localization to the immediate site of infection,
Clearance by macrophages, NK cells, polymorphonuclear cells, complement.
Adaptive immune response provides memory against subsequent infection.
Virus-specific humoral and cellular responses
If not quickly limited, acute infections are resolved by host death
e.g. many haemorragic viruses, severely immunocompromised patients
Antigenic variation – the viral response
• Survival of acute infection  lifelong immunity to that specific virus
• How is it that we get sick from other acute viruses over and over?
o e.g. common cold, influenza
• Answer: viruses capitalize on high rates of mutation to evolve around immune
• Structural plasticity: virions that can tolerate many amino acid substitutions yet
remain infections.
o Rhinoviruses and Influenzaviruses are incredibly structurally plastic.
o Limits ability to make effective vaccines
• Many viruses are not structurally plastic: e.g. poliovirus. One vaccination can
confer lifelong immunity
Structural plasticity: Antigenic variation
The immune system detects “epitopes” on “antigens”: structural features of molecules
• Antigenic variation:
o Changes in the epitopes of viral proteins that are presented to the immune
• Antigenic drift:
o Appearance of virions with slightly altered surface proteins following
passage in the natural host.
o An evolutionary process where natural selection is driven by the host
immune response
• Antigenic shift:
o A major change in a surface protein as a gene encoding a completely new
surface protein is acquired.
o Results from coinfection of one host with two different viral serotypes.
o Due to reassortment of genes among two or more viruses.
o Very commonly seen with viruses having segmented genomes.
o Reassortment and recombination of blocks of genetic information result in
viral hybrids that are immunologically new to the host.
Acute infections and Public Health
Acute infections are commonly associated with epidemics
e.g. polio, influenza, measles, common cold
Main problem: by the time symptoms emerge, the patient has passed on the infection
Difficult to control in large populations and crowded environments
e.g. work, daycare, dorms
Effective antiviral drug therapy requires early intervention, safe drugs with few side
effects…..not really practical for acute infections.
Cost: 90% of outpatient visits due to self-limiting acute viral infections.
Persistant Infections. Four general classes.
1) Infection by viruses which actively produce large amounts of progeny, but which
cause little cytopathology.
2) Infection by normally lytic virus but in which the extent of virus multiplication is
somehow limited, so that the yield of virus is small.
3) Limitation of reinfection by various viral and cellular factors, so that the proportion
of infected cells in the total cell population remains small but constant.
 Viral factors tend to be decreased virulence, and interference of virus
production by defective interfering particles.
 Cellular factors include differences in permissiveness to infection/virus
replication, and immune surveillance.
4) Chromosomal integration of proviral genomes
 Result in “silent” infections, infrequent or constant rounds of low level, and only
slight production of cytopathic virus.
Some persistent viral infections of humans (see Table 16.2)
Adenovirus Adenoids, tonsils, lymphocytes None known
Epstein-Barr B-cells, nasophayngial epithelia Lynphoma, carcinoma
H.Cytomegalovirus Kidney, salivary gland, WBCs? Pneumonia, retinitis
Hepatitis B virus Liver, lynphocytes Cirrhosis, liver cancer
Hepatitis C virus Liver Cirrhosis, liver cancer
HIV CD4+ T-cells, macrophates, AIDS
HSV 1 and 2 Sensory and autonomic ganglia Cold sore, genital herpes
HTLV 1 and 2 T-cells Leukemia, brain infections
Papillomaviruses Skin, epithelial cells Papillomas, carcinomas
Polyomavirus BK Kidney Hemorrhagic cystitis
Polyomavirus JC Kidney, CNS Progressive multifocal
Measoes CNS Subacute sclersoing
Rubella virus CNS Progressive rubella
Varicella-Zoster Sensory ganglia Shingles, postherpetic neuralgia
Perpetuating a persistent infection by modulating the adaptive immune response:
Blocking display of viral antigen in context of MHC class I (See Fig. 16.5).
 CTL response clears out virus infected cells
 Requires CD8 interaction with MHC class I molecules displaying viral

 The ability of an infectious agent to cause disease. A relative term in the sense

that it depends on the particular host that is infected and the state of that host as

well as the site of infection.

o Rabies and Ebola are highly virulent.

o Some viruses infect animals but are virulent only when the host immune

response is suppressed. Examples are certain herpes and hepatitis B virus

that become virulent when human hosts are treated with

immunosuppressant drugs after organ transplant.

General patterns of infection (Fig. 16.1)

 Acute

 Persistent

 Latent, reactivating

 Slow

Acute Infections

• Acute infections only detected by clinical symptoms.

• Can be acutely infected but assymptomatic…subclincal.

• Viruses usually produce large amounts of progeny

• Rapid onset of symptoms

• Rapid resolution of infection either by

– Immune clearance or

– Death

Defense against acute infections

Most acute infections are rapidly resolved

Limited by the intrinsic and innate immune responses

Localization to the immediate site of infection,

Clearance by macrophages, NK cells, polymorphonuclear cells, complement.

Adaptive immune response provides memory against subsequent infection.

Virus-specific humoral and cellular responses

If not quickly limited, acute infections are resolved by host death

e.g. many haemorragic viruses, severely immunocompromised patients

Antigenic variation – the viral response

• Survival of acute infection  lifelong immunity to that specific virus

• How is it that we get sick from other acute viruses over and over?

o e.g. common cold, influenza

• Answer: viruses capitalize on high rates of mutation to evolve around immune

• Structural plasticity: virions that can tolerate many amino acid substitutions yet

remain infections.

o Rhinoviruses and Influenzaviruses are incredibly structurally plastic.

o Limits ability to make effective vaccines

• Many viruses are not structurally plastic: e.g. poliovirus. One vaccination can

confer lifelong immunity

Structural plasticity: Antigenic variation

The immune system detects “epitopes” on “antigens”: structural features of molecules

• Antigenic variation:

o Changes in the epitopes of viral proteins that are presented to the immune

• Antigenic drift:

o Appearance of virions with slightly altered surface proteins following

passage in the natural host.

o An evolutionary process where natural selection is driven by the host

immune response

• Antigenic shift:

o A major change in a surface protein as a gene encoding a completely new

surface protein is acquired.

o Results from coinfection of one host with two different viral serotypes.

o Due to reassortment of genes among two or more viruses.

o Very commonly seen with viruses having segmented genomes.

o Reassortment and recombination of blocks of genetic information result in

viral hybrids that are immunologically new to the host.

Acute infections and Public Health

Acute infections are commonly associated with epidemics

e.g. polio, influenza, measles, common cold

Main problem: by the time symptoms emerge, the patient has passed on the infection

Difficult to control in large populations and crowded environments

e.g. work, daycare, dorms

Effective antiviral drug therapy requires early intervention, safe drugs with few side

effects…..not really practical for acute infections.

Cost: 90% of outpatient visits due to self-limiting acute viral infections.

Persistant Infections. Four general classes.

1) Infection by viruses which actively produce large amounts of progeny, but which

cause little cytopathology.

2) Infection by normally lytic virus but in which the extent of virus multiplication is

somehow limited, so that the yield of virus is small.

3) Limitation of reinfection by various viral and cellular factors, so that the proportion

of infected cells in the total cell population remains small but constant.

 Viral factors tend to be decreased virulence, and interference of virus

production by defective interfering particles.

 Cellular factors include differences in permissiveness to infection/virus

replication, and immune surveillance.

4) Chromosomal integration of proviral genomes

 Result in “silent” infections, infrequent or constant rounds of low level, and only

slight production of cytopathic virus.

Some persistent viral infections of humans (see Table 16.2)

Adenovirus Adenoids, tonsils, lymphocytes None known

Epstein-Barr B-cells, nasophayngial epithelia Lynphoma, carcinoma

H.Cytomegalovirus Kidney, salivary gland, WBCs? Pneumonia, retinitis

Hepatitis B virus Liver, lynphocytes Cirrhosis, liver cancer

Hepatitis C virus Liver Cirrhosis, liver cancer

HIV CD4+ T-cells, macrophates, AIDS

HSV 1 and 2 Sensory and autonomic ganglia Cold sore, genital herpes

HTLV 1 and 2 T-cells Leukemia, brain infections

Papillomaviruses Skin, epithelial cells Papillomas, carcinomas

Polyomavirus BK Kidney Hemorrhagic cystitis

Polyomavirus JC Kidney, CNS Progressive multifocal

Measoes CNS Subacute sclersoing

Rubella virus CNS Progressive rubella

Varicella-Zoster Sensory ganglia Shingles, postherpetic neuralgia

Perpetuating a persistent infection by modulating the adaptive immune response:

Blocking display of viral antigen in context of MHC class I (See Fig. 16.5).

 CTL response clears out virus infected cells

 Requires CD8 interaction with MHC class I molecules displaying viral