Lecture 12 - Pathogenesis of Viral Infections I Flashcards
Proportion of the population infected with a herpesvirus
98%
Why does most contact with viruses not result in symptoms?
1)
2)
3)
1) Particles don’t find a cell to infect
2) Particles are destroyed or inactivated as they enter the host
3) Infections don’t progress beyond one or two host cells
How can viral sensitivity to heat, drying or sunlight (UV) be overcome?
Produce a large number of viral particles
How can viruses avoid contact with the outside environment?
Insect vectors (arboviruses) Transfer via body fluids. Not outside host for long
What must a virus do to cause infection?
1)
2)
3)
1) Gain entry to body
2) Multiply and spread
3) Target appropriate organ
How can a virus be maintained in nature?
1)
2)
3)
1) Shed into the environment
2) Taken up by an arthropod vector or needle
3) Passed congenially (mother to foetus transmission)
Example of a systemic infection
Polio.
Enters via faecal/oral route, spreads to CNS
Example of a local infection
Influenza.
Enters, replicates, is transmitted from respiratory tract
What determines the length of infection?
Immune response of the host
Tropism of a virus
Anatomical localisation of a virus
Does the human body present many ways for a virus to enter?
No. A limited spectrum of entry sites is provided
Viruses transmitted to the skin via mechanical trauma 1) 2) 3) 4) 5)
1) HPV
2) HIV
3) HSV
4) HBV
5) Poxvirus
Viruses transmitted by injection
HBV, HIV
Virus transmitted by bite of an infected animal
Rabiesvirus
General behaviour of viruses that infect via the skin
Don’t multiply locally, but migrate to other tissues.
EG: HBV, arboviruses enter bloodstream. Rabiesvirus migrates along nerves
Most important site of viral entry
Respiratory tract
How do viruses enter the respiratory tract
Via aerosol inhalation or mechanical transmission of infected nasal secretions
Sites of virus deposition by droplet size
1)
2)
3)
1) Over 10 micrometers - Lodge in nose
2) Between 5-10 micrometers - Lodge in airways
3) Under 5 micrometers - Enter alveoli
Barriers to infection of the respiratory tract 1) 2) 3) 4) 5)
1) Mucus
2) Cilia
3) Alveolar macrophages
4) Temperature gradient
5) IgA
How do viruses infect the respiratory tract?
Bind to receptors on epithelial cells
Amount of mucus produced per day by a healthy person
20-200mL per day in nose and lungs
How fast does the muco-ciliary elevator move liquid from lungs to oesophagus?
~1cm/minute
Viruses that can infect the LRT 1) 2) 3) 4)
1) Parainfluenza virus
2) Respiratory syncitial virus
3) Influenza virus
4) Adenovirus
Viruses that can infect the URT 1) 2) 3) 4) 5) 6) 7)
1) Rhinovirus
2) Parainfluenzavirus
3) Respiratory syncitial virus
4) Influenza virus
5) Adenovirus
6) Herpes simplex virus
7) EBV
Hepatitis that can be sexually transmitted
HBV
Viruses that cause local GIT infection
Rotavirus, coronavirus, adenovirus
Viruses that enter via the GIT to cause systemic infection
Enteroviruses, hepatits A
Virus survival requirements if infecting the GIT
Acid stability
Resistance to bile salts (basic)
Resistance to inactivation by proteolytic enzymes (in the case of reoviruses, proteolytic cleavage is necessary)
Cell often used by viruses to infect the small intestine
M cells
Only enveloped viruses that can infect the GIT
Coronaviruses.
Can be protected from acid by association with milk products
How can a virus infect GIT if it lacks receptors for epithelial cells?
HIV, Hep B can infect anal route via abrasions in epithelium
Viral spread beyond site of infection
Disseminated
Viral spread beyond site of infection, affecting multiple organs
Systemic
Examples of local respiratory viruses
Influenza, rhinoviruses, respiratory syncitia virus
Example of local dermatological virus
HPV
Example of local GIT virus
Rotavirus
How can viruses target whether to become local or systemic?
Target viral budding to apical or basal surface of host cell.
This might occur via viral glycoproteins.
Viremia
Presence of viral particles in the blood
Types of viremia
Passive viremia - Viral particles introduced to blood without viral replication at the site of entry (EG: injection, animal bite)
Active viremia - Presence of newly-synthesised virions in blood
Where can viruses be during viremia?
Free in blood, or within infected cells in blood
Primary and secondary viremia
Primary - Released from infected cells at the site of entry. Lower viral titres.
Secondary - Virus has infected a different target organ to the site of entry (often the spleen or liver). Larger viral titres, more prolonged viremia.
How is viremia in plasma neutralised?
Neutralised by antibodies, removed by macrophages
How long does it take for the body to control viremia free in the plasma?
1-2 weeks for a neutralising antibody response
Examples of viruses causing cell-associated viremia
Measles
HIV
Measles and HIV spread in monocytes. HIV spread in CD4+ T cells
Days after infection that primary viremia can occur
~2 days
Days after infection that secondary viremia can occur
~4-14 days
Stages of viremia in mousepox
Primary viremia after two days, replication occurs in skin, regional lymph nodes
Secondary viremia after five days. Replication in spleen and liver.
Haematogenous spread
Epithelium at body surface drains into lymphatic capillary.
This drains to lymph node, which drains to venous system
Different strategies of tissue invasion from the blood 1) 2) 3) 4)
1) Some viruses can infect endothelial cells in blood vessels, infect tissues from the blood
2) Transport across endothelial cells via transcytosis
3) Virus can infect monocytes or lymphocytes, which can cross from blood into tissues
4) Some tissues aren’t joined via tight junctions. EG: mumps moves between cells of chorioid plexus from blood into the brain
How do viruses spread neurally? 1) 2) 3) 4) 5)
1) Via peripheral nerves (EG: HSV, varicella, rabies)
2) Uncoated nucleocapsid is carried passively along axons or dendrites
3) Virus multiplies in nerve body. Progeny can cross synaptic junction, infect CNS
4) Protected from CD8+ attack, as neurons lack MHCI
5) Some viruses enter directly from blood
Rabiesvirus neural spread 1) 2) 3) 4) 5)
1) Replicates at site of infection (often myocytes) until enough viral particles come into contact with sensory or motor nerve cells
2) Virus enters axons where they aren’t myelinated
3) Move to neuron nucleus via retrograde axoplasmic flow
4) Rabies reaches spinal cord. Clinical rabies occurs when neuronal dysfunction begins.
5) Virus travels along peripheral nerves via anteretrograde axoplasmic flow to salivary glands.
How quickly does rabies virus travel along axons?
Slowly.
~10-20mm/day
Virus that travels from a reservoir to epithelium via anteretrograde transport
Herpesvirus
Spread of varicella zoster (herpesviridae)
Day 0) Infection of conjunctiva and URT
- Viral replication in local lymph nodes
Day 4-6) Primary viremia in bloodstream
-Further replication in liver and spleen. Secondary viremia/
Day 10) Infection of skin, vesicular rash
Virus that uses both viremia and neural spread
Variacella zoster.
Viremia from replication in lymph nodes, spleen, liver.
Dormancy in dorsal root ganglia
Viruses that kill foetuses
Cytocidal viruses
Viruses that result in abnormalities of foetuses
Non-cytocidal viruses
Viruses that can infect a baby at birth
1) HSV, varicella, CMV (infected birth canal)
2) Coxsackie B (faecal contamination)
Spread of viruses that cause acute respiratory disease
High titres shed for a short period (~1 week). Influenza, rhinovirus
Time of peak infectiousness of measles
Prior to onset of rash
Places from which viruses can be excreted in faeces
From epithelial cells lining intestinal tract (rotavirus)
From the liver via the bile duct (Hep A)
How is HPV spread?
Only from the top layer of infected skin. Transmitted via mechanical contact. Blood from wart has very high viral titre.
How is varicella spread?
Shed from virus-filled vesicles.
Can be spread from respiratory tract (aerosolised)
Is the measles rash infectious?
No
Which viruses are normally spread via blood?
Viruses that result in persistent viremia
Why does direct human-human or human-arthropod-human transmission not often occur with arboviruses?
Levels of virus in the blood are too low
How is CMV secreted?
Urine, saliva, tears, breast milk, semen, cervical secretions
How is EBV spread?
Saliva
How is HIV transmitted?
Milk, semen, cervical secretions, blood
