Lecture 21: Dissemination,
Virulence, and Epidemiology
Text: Flint et al, Chapter 14
General points
• To establish a successful infection, viruses must
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Find a way to enter the host
Find a way to get through the host defences
Move through the host
Find the right cell types to infect
• To spread infection, viruses must
– Find a way for new viral progeny to exit infected cells
and host
– Find a way to survive outside of host
Initiation of infection
•
Sufficient virus must be available
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High concentrations.
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High survivability in harsh exterior
environments
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Dilution
pH changes
Dissecation
Cells at site of infection must be
1.
2.
3.
•
A sneeze droplet contains up to 100
million Rhinovirus particles.
Similar amount of Hepatitis B in 1ml
of infected blood.
Accessible
Susceptible
Permissive
Local host defenses must be
–
–
Absent or
Initially ineffective
Viral Entry: respiratory tract
• Common route for viruses
• Aerosolized droplets
– Coughing, sneezing
– Large droplets deposited in nose
– Smaller ones further down the Resp. tract
• Must overcome
– Clearance by mucus
– Inactivation by antibodies
– Destruction by macrophages.
Viral Entry: respiratory tract
Fig. 14.2
Viral Entry: alimentary tract
• Common route of entry and dispersal
• Virus must be resistant to
– Stomach acids
– Bile bases (detergents)
• Destroys most enveloped viruses.
• Somehow many Coronaviruses survive
– Proteases
• Many viruses, e.g. Reovirus particles, are actually
activated by intestinal proteases.
Viral Entry: into M cells
Viral Entry: into M cells
• Most of gut is lined with columnar villous epithelial cells.
– Apical sides are densely packed with microvilli
– “Brush border” coated with glycoproteins, glycolipids and mucus
– Difficult to penetrate
• M cells: lymphoid cells scattered throughout gut
– Thin, absorptive,
– Normally transmit antigens to underlying lymphtocytes via
transcytosis
• Some viruses infect only M cells
– e.g. Rotavirus, Coronavirus transmissible gastroenteritis
– Lyse M cells, cause mucosal inflammation, diarrhea
– Others transcytose through M cells into underlying basal
membranes and extracellular space. e.g. Reoviruses
– From there, can go to
• Lymphatic system
• Circulatory system
• Rest of host
Viral Entry: through Urogenical tract
–Physical barriers: mucus, low pH (vagina only)
–Viral entry via tears and abrasions due to
normal sexual activity
–Viruses can infect epithelium and cause local
lesions, e.g. some papillomaviruses
–Others infect underlying tissues, and invariably
spread and persist
»Neurons, e.g. herpesviruses
»Lymphoid tissue, e.g. HIV
Viral Entry: through eyes
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Physical barriers: tears, mucus, proteases
Entry via abrasions, poor sanitation
Most infections are localized: conjunctivitis
Herpesvirus Type I infections can spread
to neurons and become persistent
Viral entry: through skin
• Presents formidable
physical barriers
• Entry via breaks in
skin
• Abrasions, e.g.
papillomaviruses:
usually local
• Insect bites, e.g.
West Nile
• Animal bites, e.g.
rabies
• Behavior: needles,
tattoos, body piercing
Fig. 14.4
Evasion of host defenses
• Active and passive mechanisms
• Active: knock out immune mechanisms
• Passive:
– Overwhelming numbers
– Infect immunonaive organs, e.g. Rabies
Kinetics of viral replication and immune response
Fig. 14.5
Viral Spread
• After replication at site of entry, virus can
– Remain localized
• e.g. rhinovirus in respiratory epithelium
– Spread to other tissues
• e.g. polio from gut epithelium to neural tissues
• Disseminated infection – virus spread to other
tissues
• Systemic infection – virus spread to many
organs
• Shedding – release of virus from infected
cells/tissues
Polarized viral spread
• Direction of virus particle
release determines how
virus will spread
• Release at apical
membranes: localized or
limited infection
– e.g. Influenza
• Release at basal
membranes:
disseminated/systemic
infections
– e.g. VSV
Fig. 14.6
Vessicular Somatitis Virus
Hematogenous Spread
• Spread through the
blood.
• Virus replicates at site
of entry, exits infected
cells
• Enters bloodstream –
primary viremia
• Infects other organs,
replicates, exits into
bloodstream –
secondary viremia
• Replicates yet again in
other organs, exits
passed on.
Fig. 14.7
Neural spread
• Many viruses spread from primary site of infection by
entering local nerve endings
• Typically, such viruses enter from a nerve ending or
axon
• Replicate in the cell body
• Directionally exit the neuron: retrograde vs.
antiretrograde
• Routes of entry can be
– Neural: poliovirus, herpesviruses
– Olfactory: herpesviruses, coronaviruses
– Hematogenous: polio, coxackievirus, mumps, measles, CMV
Neural spread
Box 14.3.
anterograde vs
retrograde
spread
Fig. 14.11 pathways
of neural spread
Fig. 14.12: olfactory spread
Organ invasion
• From viremia, subsequent replication requires invasion of
new cells and tissues
• Three main types of blood vessel-tissue interfaces provide
routes for invasion
1. Capillary: very tight basement membrane
2. Venule: contains pores through basement membrane
3. Sinusiod: very leaky, macrophages form part of blood-tissue junction
Fig. 14.13
Viral
entry
routes
into the
liver
Fig. 14.15
Virus shedding and transmission
Shedding: release of infectious viruses from infected host
• Respiratory secretions. e.g rhinoviruses, influenza viruses
– Aerosolization – sneezing, coughing
– Contamination of fomites by nasal secretions
• Saliva. e.g. mumps, cytomegalovirus, rbies
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Aerosolization – sneezing, coughing
Contamination of fomites – spitting, coughing, wiping hands
Kissing, grooming (animals)
Animal bites
• Feces, e.g. enteric and hepatic viruses
– Poor sanitation, food contamination, sexual exchange
• Blood, e.g. sindbis viruses (West Nile), Denge virus, hepatitis, HIV
– Transmission by biting insects, during sex, childbirth, exposure to
contaminated blood
• Urine (viruea)
– Hantaviruses, arenaviruses
• Semen
– HIV, some herpesviruses, hepatitis B
• Milk
– Mouse Mammary tumor virus, Mumps, CMV
• Skin lesions
– Poxviruses, HSV, varicella zoster, papillomaviruses, Ebola virus
Epidemiology
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5.
6.
Definition: The study of the occurrence of a
disease in a population.
Includes:
Mechanisms of viral transmission
Risk factors for infection,
Population size required for virus transmission
Geography
Season
Means of control
Mechanisms of viral
transmission
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Aerosol
Food and water
Fomites
Body secretions
Sexual activity
Birth
Transfusion/transplant
Zoonoses (animals, insects)
Factors that promote
transmission
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Virus stability
Virus in aerosols and secretions
Asymptomatic shedding
Ineffective immune response
Geography and Season
• Vector ecology; School year; Home heating season
Risk factors
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Age
health
immunity
occupation
travel
lifestyle
children
sexual activity
Critical
population size
Numbers of
seronegative
susceptible
individuals
Means of control
• Quarantine – SARS
• Vector elimination – mosquito control and
West Nile
• Immunization – MMR, DPT, etc…
• Antivirals – triple therapy and AIDS