Viral pathogenesis Flashcards
Incubation period
Initial period before disease symptoms are obvious
- can be transmitted
- Signs are present:
Viral genomes replicating
Host is responding
Incubation periods for various diseases
Arbovirus - short (>1week)
Measles - Medium (7-21 days)
Rabies- Long (weeks to months)
Prion diseases; measles/subacute sclerosing panencephalitis - Very long (Usually fatal or years)
Disease patterns
Acute non persistent
Latent
Persistent - asymptomatic
Persistent pathogenic
Insidious infections with fatal outcomes
Dissemination of infection
movement of virus once it penetrates the epithelium
Directional release of virus from polarised cells can influence the outcome of the infection
Apical release
Virus release to internal lumen side of epithelial cells
Virus does not usually invade underlying tissues
Basolateral Side
Virus releases to external tissues
Virus has access to underlying tissues and this may allow systemic spread
Hematogenesis Spread
Entry of viruses via bloodstream
Can occur via dissemination from epithelial infection or inoculation by a vector bite into capillaries
Replicated viruses in extracellular fluid can be taken up by Lymphatic vessels and drained into the circulatory system
Lymphatic systems in virus spread
Lymphatic systems drain extracellular fluid into the bloodstream giving a pathway to viruses
With lymphatic vessels viruses can also be exposed to lymphocytes they may be tropic for
Viraemia
describes the presence of
infectious virus particles in the blood
amount of virus in blood
Active viremia
Class of Viremia
produced by virus replication
Passive viremia
virus particles are introduced
into the blood without viral replication at the site
of entry
Secondary viremia
subsequent disseminated
infections; appearance of a high concentration of
infectious virus in the blood
Pathogenesis of measles from virus infection to recovery
- virus entry via respiratory tract
- primary replication
- spread and tropism
- cell injury and clinical illness
- recovery from infection - immunosuppression
- virus spreading and transmission
Organ invasion
Post dispersal from infection site into blood invasion of new cells and tissues is required for replication
3 main types of blood vessel/tissue junction for virion entry
continuous endothelium and basement membrane found in CNS, connective tissue, muscle, skin and lungs
Fenestrated epithelium found in choroid plexus, intestinal villi, renal glomerulus, pancreas, and endocrine glands
Sinusoid, lined with macrophages of the reticuloendothelial system, as found in adrenal glands, liver, spleen and bone marrow
Liver, spleen, bone marrow and adrenal glands
Organs all characterised by the many gaps (sinusoids), lined with macrophages
Macrophages are often infected by viruses in the blood, making these areas highly susceptible
CNS, Connective tissue and skeletal and cardiac muscle
endothelial cells are backed by a dense basement membrane
In the CNS the basement membrane is the foundation of the BBB
Viruses may pass though via the CSF into the brain
May also cross BBB in cells or via transcytosis
Neural spread
Spread via the infection of nerve endings
Termed “neurotropic”
Virus usually infects cells of the PNS first and then spreads to the spinal cord
Aseptic meningitis
inflammation of the meninges caused by increased mononuclear cells
- viral infection most common cause
- non infectious causes do occur
Encephalitis
Infection and inflammation of the brain
May be cause of an acute infection or the complication of a latent virus
Mostly caused by enterovirus, HSV, rabies, arboviruses
encephalomyelitis
inflammation of the spinal cord and brain
meningoencephalitis
Encephalitis with meningitis
Symptoms of meningoencephalitis
Symptoms: headache, fever, confusion, drowsiness; more
advanced disease includes convulsions, seizures, hallucinations,
memory loss and coma; can be fatal
Acute flaccid paralysis
Acute flaccid paralysis
- symptom of CNS viruses
- May be caused by anterior horn cell infection with wild or vaccine polio virus, or other viruses ʹ e.g. Enterovirus 71
HIV
HIV enters the nervous system early, at the time of initial infection, and may immediately cause symptoms, or may cause symptoms across a person’s lifetime
HIV in the nervous system
easily crosses the BBB
Causes: AIDS Dementia Complex (brain), Vacuolar Myelopathy (spinal cord), Peripheral Neuropathy (nerve), Meningitis (acute or chronic)
Zika virus in babies
Zika virus infection during pregnancy can cause infants to be born with microcephaly and other congenital malformations, known as congenital Zika syndrome and preterm birth or miscarriage
Viral shedding
Viruses shed from an infected host can infect new susceptible hosts
Viruses may be shed from primary site of multiplication or from target organ
Healthy individuals may shed viruses continuously – HSV in saliva; CMV in urine and
breast milk; viruses infecting GIT in faeces and vomit
R0
R0 is 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
Types of viral transmission
latrogenic: activity of a healthcare worker leads to infected patient
Nosocomical: individual is infected in hospital or healthcare settings
Vertical: from parents to offspring
Horizontal: all other forms of transmission
Germ line: transmission as part of the host genome
