Viruses and Pathogenicity

Question 1

What mediates defence against microbes?

Answer 1

Effector mechanisms of innate and adaptive immunity

Question 2

What does innate immunity provide?

Answer 2

Early defence

Question 3

What does adaptive immunity provide?

Answer 3

A more sustained and stronger response

Question 4

What influences the survival and pathogenicity of microbes?

Answer 4

The ability of the microbes to evade or resist effector mechanisms of immunity

Question 5

In what case does the immune response control but not eliminate a microbe?

Answer 5

If the microbe established latency or persistent infection

Question 6

What is immunopathology?

Answer 6

Tissue injury and disease cause by the host response to the microbe rather than the microbe itself

Question 7

What is a virus?

Answer 7

A small infectious agent that replicates only outside the living cells of other organisms

Question 8

What do viruses show?

Answer 8

Restricted species specificity

Question 9

Why do viruses have such wide diversity?

Answer 9

There is no single origin of virus life

Question 10

What are some common virus diseases of man?

Answer 10

Influenza
Common cold
Measles
Mumps
COVID-19
Chickenpox/shingles
Glandular fever
Hepatitis
Papillomas
AIDS
Kaposi’s sarcoma

Question 11

What are the general patterns of viral infection?

Answer 11

Acute infection
Latent/reactivating infection
Persistent infection

Question 12

Describe acute infections

Answer 12

A huge spectrum of disease and range of outcomes
Can be resolved by immunity but sometimes is not

Question 13

What is an example of latent/reactivating infections?

Answer 13

Human Herpes Viruses - life-ling, controlled by immunity

Question 14

What are the types of human herpes viruses?

Answer 14

Herpes simplex virus type 1 (HHV-1)
Herpes simplex virus type 2 (HHV-2)
Varicella zoster virus (HHV-3)
Epstein-Barr virus (HHV-4)
Cytomegalovirus (HHV-5)
Human herpesvirus 6 (HHV-6)
Human herpesvirus 7 (HHV-7)
Human herpesvirus (HHV-8)

Question 15

Describe HHV-1

Answer 15

Primary gingivostomatitis
Cold sore

Question 16

What viruses persist in the presence of an active immune response?

Answer 16

HIV - retrovirus
HCV - flavivirus
Measles - causes acute infection but virus sheds for several weeks after acute infection and rare encephalitis cases years after infection
All controlled by immunity

Question 17

What viruses persist in the absence of an active immune response?

Answer 17

Lymphocytic Choriomeningitis Virus (LCMV)
Pestiviruses (e.g. BVDV)
Congenital Rubella
All controlled by immunotolerance

Question 18

Describe LCMV

Answer 18

First virus associated with aseptic meningitis in humans
Causes severe neurological damage
Not spread between people - zoonotic infection acquired from rodents
Secreted in urine by rodents
Infected rodents are persistently infected and show life-long secretion and have no obvious illness

Question 19

Describe bovine viral diarrhoea virus (BVDV)

Answer 19

Usually a classical acute infection
Makes the animals sick and immunosuppressed for a couple of weeks
Virus can be spread by aerosols and faeces
Reservoir is a small pool of persistently infected animals
The animals acquire the virus when they are foetuses, before the development of any adaptive immune response in a largely asymptomatic infection
Animals see the virus as self
Animals constantly shed the virus
Eventually the virus mutates and generates a cytopathic virus that kills the animal because they do not see it as foreign

Question 20

Describe congenital rubella

Answer 20

Rubella virus viremia can infect placenta of a pregnant woman and viral replication can infect all foetal organs
Causes huge amount of tissue damage
Hallmark of foetal infection is chronic infection that persists throughout foetal life, with shedding of virus up to 2 years after birth
Viral shedding by infants with congenital rubella syndrome can result in outbreaks

Question 21

Describe inapparent infections

Answer 21

90% of all poliovirus infections are asymptomatic (inapparent)
Many people get infected with parainfluenzavirus 5 without clear symptoms, yet this often gives rise to very mild respiratory disease
Inapparent infections occur only if the viruses are non-cytopathic and host-adapted

Question 22

How does virus infection of a host lead to disease?

Answer 22

Pathogenesis results from cell and tissue damage cause by the viral infection
Clearly associated with cytopathic viruses
On most occasions the damage is limited by the host’s immune system

Question 23

Describe some viruses that cause cytopathic damage

Answer 23

EBOLA targets vascular endothelial cells
Influenza A virus targets lung epithelia
RSV induces syncytia in lung epithelia

Question 24

Describe hepatitis C virus (HCV)

Answer 24

Non-cytopathic
Associated with extensive liver infiltration of leukocytes
High levels of pro-inflammatory cytokines
Viral clearance and disease is associated with generation and infiltration of CD8+ cells which attack infected cells and destroy them
HCV persistence is associated with generation of HCV variants that are not recognised by CD8+ cells

Question 25

Describe Dengue virus

Answer 25

Most common mosquito-borne infection worldwide
4 serotypes with have the same clinical manifestations
Symptoms include malaise, high fever, headache, generalised arthralgia and myalgia
Severe dengue can occur which may include dengue shock syndrome (DSS) and haemorrhage

Question 26

Describe Dengue virus

Answer 26

Most common mosquito-borne infection worldwide
4 serotypes with have the same clinical manifestations
Symptoms include malaise, high fever, headache, generalised arthralgia and myalgia
Severe dengue can occur which may include dengue shock syndrome (DSS) and haemorrhage

Question 27

What is the greatest risk in dengue infection?

Answer 27

A previous infection with a different serotype
Abs formed in response to a dengue infection are not cross-protective against other subtypes of the virus
May result in more severe disease due to antibody-dependent enhancement (ADE)

Question 28

Describe ADE

Answer 28

Non-neutralising Abs coat the virus, forming immune complexes
These are internalised into mononuclear phagocytes through Fc receptors
Fixation of complement by circulating immune complexes results in release of products of the complement cascade
Leads to sudden increased vascular permeability, shock and death