12 - Viral Pathogenesis Flashcards
Requirements for successful infection
- Dose (enough virus)
- Access to target cells (susceptible, permissive)
- Absent or insufficient host immunity
Short incubation period
- <1 week
- Localised infections
- Arboviruses (viruses transmitted by mozzies)
Medium incubation period
- 7-12 days
- Generalised infections
- Measles
Long incubation periods
- Weeks to months
- Rabies
Very long incubation periods
- Years
- Usually fatal
- Prion diseases
Latent
Persistence of viral genome in the host cell and periodic virus reactivation
Viral pathogenesis
complex interaction between virus and host that results in disease
Viral pathogenesis stages
- Entry and primary replication
- Viral spread and cell tropism
- Cell injury and clinical illness
- Recovery from infection
- Virus shedding and transmission
- Host immune response
Pathogenicity
the comparison of the severity of disease caused
by different microorganisms
Virulence
comparison of the severity of disease caused by
different strains of the same microorganism
Viruses endemic in rodents
Hemorrhagic disease viruses (e.g. Lassa, Junin, Sin Nombre)
dead end host
Effect host but not transmitted between hosts
Entry through the skin
- Abrasions (HPV)
- Inoculation with contaminated needles (HIV, Hep B and C)
- Insect or animal bites (Dengue, rabies)
Entry through mucous membranes
- Respiratory tract (Influenza)
- Gastrointestinal tract (faecal-oral route, Poliovirus)
- Conjunctiva (Adenoviruses,)
- Genital tract (HSV, HIV)
- Transplacental (congenital, vertical: HSV, Rubella)
Apical release
virus does not usually invade
underlying tissues
Basolateral release
virus has access to underlying tissues and this may allow systemic spread
Which release causes disseminated infection
Release from both apical and basal surfaces
Haematogenous spread
- Viruses taken up by the local lymphatic vascular system, replicate in endothelial cells or
inoculation by a vector bite. - Access almost every tissue in the host
Viraemia
Presence of infectious virus particles in the blood
Active viraemia
produced by virus replication
Passive viraemia
virus particles are introduced into the blood without viral replication at the site of entry
Secondary viraemia
subsequent disseminated
infections, appearance of a high concentration of
infectious virus in the blood
Cellular factors of viral invasion of the host
- Presence of appropriate receptors
- Physical and molecular environment must enable initial replication cycle (temperature, pH)
Lysis
- Virus-encoded proteins may shut down synthesis of cell macromolecules
- accumulation of viral proteins may inhibit host cell function.
- Cell death is followed by lysis and release of viral particles
Syncytium formation
- fusion of an infected cells with neighbouring cells leading to the formation of multinucleate enlarged cells (syncytia)
- allows viruses to pass from cell to cell, instead of being released via lysis
Ananthem
Rash on mouth mucosa
Vesicular eruptions
Viral replication in the skin (herpes)
Maculopapular rash
destruction of infected cell by cytotoxic T lymphocytes (measles)
Purpuric rash
Thrombocytopenia (Dengue)
Haemorrhagic rash
result of disseminated intravascular coagulopathy
Disseminated
Spread of virus beyond primary site
Systemic
Infecting many different organs
Important target organs of dissemination
- Lungs
- Liver
-CNS
Lungs
- Most respiratory infections are localised
- Some are generalised (measles)
Liver
- Target for hepatitis viruses
- Infected during generalised infections (e.g. yellow fiver)
CNS
- Access from bloodstream during viraemia (e.g. Polio)
- Via peripheral nerves (Herpes, Rabies)
Dissemination pathway of herpes
- Virus inoculated
- Viral replication in muscle
- Virus binds to nicotinic acetylcholine receptors at neuromuscular junction
- Virus travels within axons in peripheral nerves (retrograde axonal transport)
- Replication in motor neurons of the spinal cord and local dorsal root ganglia and rapid ascent to brain
- Infection of brain neurons with neuronal dysfunction
- Centrifugal spread along nerves to salivary glands, skin, cornea
Aseptic meningitis (not caused by pyogenic bacteria)
- Inflammation of the meninges
- Viral infection is the most common (enterovirus)
Encephalitis
- Inflammation of the brain
- Headache, confusion, seizures, hallucinations
- Can be fatal
- Enterovirus, HSV, rabies, arboviruses
Acute flaccid paralysis
- acute onset of flaccid
paralysis in one or more limbs - Caused by anterior horn cell infection with wild or vaccine polio virus
What can primary HIV disease lead to
- AIDS Dementia complex (brain)
- Vacuolar Myelopathy (spinal cord)
- Peripheral Neuropathy (nerve)
- Meningitis (acute or chronic)
Zika virus
- Spread by mosquitos
- Most cases asymptomatic, mild flu like symptoms
- Increased risk of Guillain-Barré Syndrome
- Vertical transmission causing microcephaly and other congenital brain abnormalities
- Sexual transmission and blood-transfusion (WHO)
Reproduction number (R0)
- The average number of secondary cases generated
by one primary case in a susceptible community - The higher the R0, more persons infected from one
primary case
Viral shedding
- Viruses shed from an infected host can infect new susceptible hosts
- May be shed from primary site of multiplication or from target organ
- Healthy individuals may shed viruses continuously (e.g. HSV in saliva)
