L4 The Mysterious Bugs

Question 1

Zika virus

Answer 1

causes birth defects - microcephaly (undeveloped heads and brain damage)

Linked to Gullian-Barre syndrome - immune system attacks the nerves (spread through mosquitoes)

Question 2

Virion

Answer 2

Nucleic acid - DNA/RNA, ds or ss & +ve/-ve/ambisense

Protein coat - enveloped/unenveloped

Question 3

Nucleocapsid

Answer 3

Nucleic acid and protein coat

Question 4

Virus problems

Answer 4

Must replicate inside cell
Must move from one infected cell to new one
Must develop mechanisms to evade host defences

Question 5

Mechanisms of viral pathogenesis

Answer 5

Implantation at portal of entry
Local replication
Spread to target organs (lymphatic system)
Multiply in target organs
Spread to the sites for viral shedding into atmosphere

Question 6

Mechanisms of disease at target cell

Answer 6

Infect cells produce dysfunction
Toxic products of viral replication and cell necrosis
Inflammatory mediators & lymphokines
Immunosuppression - secondary infection

Question 7

Shedding of virus [8]

Answer 7

• Respiratory tract
	• Alimentary tract
	• Blood stream
	• Semen and/or Genital tract
	• Milk
	• Urine
	• Saliva
Germ cells

Question 8

Routes of transmission

Answer 8

Skin/mucous membrane 
Respiratory tract
Faecal oral
Blood borne
Sexual transmission

Vertical transmission - mother to baby
○ Antenatal e.g. transplacental
○ Perinatal
○ Postnatal – e.g. breast milk

Question 9

Chronic vs Acute

Answer 9

Acute: virus infects susceptible host

Chronic/persistent: continues infection beyond time when immune system should have cleared it

Acute infection – non equilibrium process
host response & virus infection change continually until resolution
Chronic – equilibrium between virus & host
balance until equilibrium changes

Question 10

Virulence [4]

Answer 10

Replication efficiency
Cell tropism
Host response
Interaction between virus and host

Can lead to rapid death, induce cancer over long periods and organ failure

Question 11

Chronic vs Acute mechanisms

Answer 11

Continuous replication & latency

Restricted viral gene expression, no viral proteins & immunologically silent

Question 12

Latent infection

Answer 12

DNA viruses or retroviruses

Persistence of viral DNA (Extrachromosomal element (herpesviruses) &
Integrated within the host genome (retroviruses))

During cell growth the viral genome is replicated along with the host cell chromosomes

Retrovirus infection may result in transformation of the cell leading to cancer

Question 13

Herpes simplex virus type 1 or 2 (HSV) reactivation

Answer 13

Fever, blisters or cold sores

Question 14

Retrovirus infection may…

Answer 14

Retrovirus infection may result in transformation of the cell leading to cancer

Question 15

Reactivated endogenous viruses

Answer 15

Shingles (VZV)
Recurrent oral & genital herpes (HSV)
CMV infections

Immunosurveillance
Aging or immunosuoression

Question 16

Endogenous vs exogenous

Answer 16

Endogenous is within

Question 17

Tropism

Answer 17

An appropriate cell surface molecule to act as a virus receptor = “susceptibility”

Appropriate cell transcription factors to switch on viral genes, and/or cell enzyme pathways to produce viral proteins = “permissivity”

Question 18

Considering a virus

Answer 18

Where does it occur, geographically and demographically?
Is it ubiquitous/common/uncommon/rare?
What diseases and clinical syndromes is it associated with?
How does it cause disease “pathogenesis”?
How would you confirm the diagnosis?
Are there vaccines / drugs to counter it?

Question 19

What to test?

Answer 19

Blood
Swab e.g. skin lesion, throat, eye, genital, etc  
Cerebrospinal fluid
Stool (faeces)
Urine
Tissue biopsy

Question 20

Electron Microscopy

Answer 20

Needs a very high viral copy number (106) in the sample

Need expert personnel

Expensive & big machine

Question 21

Viral culture

Answer 21

Obsolete method for viral diagnosis

Embryonated hen’s egg
Currently of very limited use – vaccine production e.g. flu vaccine

Question 22

Cell culture

Answer 22

Not all viruses can grow in cell culture
Need multiple cell lines – different viruses grow in different cell lines
Slow method of diagnosis – some viruses e.g. CMV need >1 week to grow
Currently of limited use

Question 23

Immunofluorescence

Answer 23

Quick test, but not applicable for all viruses – need manufacturing of specific monoclonal antibodies (e.g. currently antibodies only available against 6 of ~15 respiratory viruses)
Need fluorescent microscope set up
Need expert personnel

Question 24

Antibody detection

Answer 24

In serum/plasma
Is called “serology”
Commonest test used is the ELISA

Chromogen or substrate which changes colour when cleaved by the enzyme attached to the second antibody
Anti-human immunoglobulin (2nd antibody) coupled to an enzyme