Viruses - what they are and pathogenesis

Question 1

Define a virus

Answer 1

• A virus is a small infectious agent that replicates only inside the living cells of other organisms. All types of life forms, from animals and plants to microrganisms,
  including bacteria and archaea have viruses
• They show restricted species specificity

Question 2

Describe the virus Life Cycle

Answer 2

(1) Virus fuses with plasma membrane, and viral DNA is released from capsid at nuclear pore followed by circularization of genome and transcription of immediate-early genes.

(2) α-Proteins, products of immediate-early
genes, stimulate transcription of early genes.

(3) β-Proteins, products of early genes, function in DNA replication, yielding concatemeric
DNA. Late genes are transcribed.

(4) γ-Proteins, products of late genes and consisting primarily of viral structural proteins, participate in
virion assembly. Unit-length viral DNA is cleaved from concatemers and packaged into capsids. Enveloped viral particles accumulate in the
endoplasmic reticulum (ER) and are transported from the cell.

Question 3

List the Human Herpes Viruses from 1-8

Answer 3

Question 4

Viruses can cause latent, reactivating infection. give an example of one

Answer 4

Human Herpes Viruses

Question 5

List examples of enveloped and non-enveloped viruses then determine whether they are ss/ds and DNA/RNA

Answer 5

Question 6

Describe Herpes Simplex & VZV latency

Answer 6

Question 7

Viruses can cause persistent infection in the presence of an active immune response, give examples

Answer 7

• HIV - retrovirus
• HCV – flavivirus
• Measles – causes acute infection, but virus shed for several weeks after acute infection, and rare encephalitis cases years after infection

Viral levels controlled by immunity

Question 8

Viruses can cause persistent infection in the absence
of an active immune response, give examples

Answer 8

• Lymphocytic Choriomeningitis Virus (LCMV)
• Pestiviruses (e.g. BVDV)
• Congenital Rubella

Controlled by Immunotolerance

Question 9

Describe Lymphocytic Choriomeningitis
Virus (LCMV)

Answer 9

• First virus associated with aseptic meningitis in
  humans; causes severe neurological damage
• Not spread between people; it is a zoonotic
  infection acquired from rodents
• It is secreted in urine by rodents
• Infected rodents are persistently infected and show
  life-long secretion, and have no obvious illness

Question 10

Describe Bovine Viral Diarrhoea Virus (BVDV)

Answer 10

• Usually a classical acute infection; makes the animals sick and immunosuppressed for a couple of weeks; symptoms very much like foot-and-mouth
• Virus can be spread by aerosols and faeces
• Reservoir of virus is a small pool of persistently infected animal. These animals acquire the virus as foetuses before the development of the adaptive immune response, in a largely asymptomatic infection
• These animals see the virus as self!
• These animals constantly shed the virus
• Eventually the virus in these animals mutates and generates a cytopathic virus that kills the animal because they do not see the virus as foreign

Question 11

Desceibe Rubella (German Measles)

Answer 11

Acute infection of healthy child

Congenital Rubella
* Rubella virus viremia can infect the placenta of pregnant women, and viral replication can infect all foetal organs. Causes huge amount of tissue damage
* The 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 12

How does virus infection of a host lead to disease?

Answer 12

*Many infections are apathogenic or associated with relatively mild symptoms; it is important to realize that from the virus’ point of view these are not always failed or resolved infections
– a successful virus is one that replicates well enough to spread to the next host

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

*On some occasions the relative limited damage caused by the virus is made worse or even caused by the host’s immune system (= immunopathology)

Question 13

Inapparent Infections

Answer 13

• 90% of all poliovirus infections are asymptomatic (inapparent)
• Many of us get infected with parainfluenzavirus 5 without clear symptoms
• Despite the bad PR ‘flu often gives rise to very mild respiratory disease
  Requires that viruses be non-cytopathic
  and host-adapted

Question 14

Cytopathic damage by ebola

Answer 14

*Its glycoprotein kills Vascular Endothelial Cells, resulting in hemorrhage
*Lymphocytes, macrophages, and dendritic cells are killed
*Hepatocytes are also killed leading to liver failure

Question 15

Cytopathic damage by infleunza A

Answer 15

Influenza A virus targets lung epithelia

Influenza virus infection causes inflammation of the
mucosa of upper respiratory tract sites such as the nose and pharynx, and lower respiratory tract sites such as the larynx, trachea, and bronchi.

the neuraminidase degrades the protective mucus layer

There is necrosis of the superficial layers of the respiratory epithelium.

Question 16

Cytopathic damage by RSV

Answer 16

RSV induces syncytia in lung epithelia

Maternal antibody passed to the infant may react with the virus, form immune complexes, and damage the respiratory tract cells.

Question 17

Describe Immunopathology and Hepatitis C Virus (HCV)

Answer 17

• Chronic hepatitis is a disease of severe liver damage and loss of hepatocytes – caused by persistent HCV infection
• HCV is non-cytopathic
• Hepatitis associated with extensive liver infiltration of leukocytes
• Pro-inflammatory cytokine levels very high
• 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 the generation of HCV variants that are not recognised by CD8+ cells

Question 18

Describe Immunopathology and Dengue Virus Infections

Answer 18

• There are 2.5 billion people at risk of dengue due to living in an endemic area, in addition to the actual living conditions.
• There are 4 serotypes (1–4), all of which have the same clinical manifestations
• Dengue fever (malaise, high fever, headache, generalized arthralgia and myalgia)
• Severe dengue, which may include dengue shock
  syndrome (DSS), and haemorrhage
  – Greatest risk is a previous infection with a different serotype
  – Antibodies formed in response to a dengue infection are not cross-
  protective against other subtypes of the virus. In fact they may
  result in more severe disease due to a phenomenon known as
  antibody-dependent enhancement or ADE
  – Non-neutralizing antibodies coat virus, forming immune
  complexes which get internalised into mononuclear phagocytes
  through their Fc receptors; fixation of complement by circulating
  immune complexes results in release of products of the
  complement cascade leading to sudden increased vascular
  permeability, shock and death

Question 19

Describe Immunopathology and cytokines

Answer 19

The virus triggers an intense cytokine storm associated with extensive immune activation during acute infection, which helps to fuel virus replication by providing a large pool of activated CD4+ target cells.