How do viruses cause disease in humans Flashcards
What is the basic reproduction number (R0)
- Is an approximate measure of how many new infections one person will generate during their infectious period
- Note that R0 values are approximate, and can vary by outbreak, mode of transmission and location
What is the duration of infection period divided into
- Incubation period and symptoms
What is the serial interval
- Time between the onset of symptoms in the primary cause and onset of symptoms in secondary cause
What is zika virus associated with in pregnant women
- Virus causes birth defects in babies born to some infected pregnant women including microcephaly
- Microcephaly is when babies are born with underdeveloped heads and brain damage
- Zika has also been linked to guillian-barre syndrome, a condition in which the immune system attacks the nerves
What is zika mainly transmitted via
mosquitoes
What is a virus
- Particle made of nucleic acid and a protein coat
- Obligate intracellular - only replicates inside living cells
How can viruses infiltrate skin
- Abrasions
- Insect/animal bites
- Needle punctures
How can viruses enter alimentary tract
- Gastroenteritis viruses
- Movement facilitate viral entry
How is the alimentary tract protective against viruses
Hostile environment
- Extreme acidity/alkalinity
- Digestive enzymes
How can viruses enter the urogenital tract
Abrasions facilitate viral entry
- HPV - local lesions
- HIV - viral spread
Urogenital tract - protective factors
- Mucus membranes
- Low pH
Eye - viral entry
- Localised infection - conjunctivitis
- Viral spread - eye blindness/CNS
Baltimore system for viral classification
I dsDNA II ssDNA III dsRNA IV +ssRNA V -ssRNA VI +ssRNA with DNA intermediate VII gapped dsDNA
Viral spread
After replication at the site of infection
- Some remain localised within epithelium or within one system
- Some cause disseminated or systemic infection (inflammation compromises integrity of cell basement membrane)
Viral release
- Apical e.g. flu - facilitate viral dispersal, but virus does not invade underlying tissues
- Basolateral e.g. rabies - provides access to underlying tissues and may facilitate systemic spread
Haematogenous spread - ways of viral entry to blood
- Directly through capillaries
- By replicating in endothelial cells
- Through vector bite
- By lymphatic capillaries
Once in the blood, virus has access to almost every tissue
Viraemia
Presence of infectious virus in the blood
- Passive/active viraemia
- Primary/secondary viraemia
Diagnostic value - measuring viral replication
Practical problem - need to screen blood donors
Neural spread
Less common than haematogenous spread
Viruses can go either way
- From peripheral sites to CNS
- From CNS to peripheral sites
Infection of the CNS
Neurotropic - virus can infect neural cells
Neuroinvasive - virus can enter CNS following infection of a peripheral site
Neurovirulent - Virus can cause disease of nervous tissue
Comparison of viruses - Neuroinvasiveness vs neurovirulence
NI NV
HSV + ++++
Mumps ++++ +
Rabies ++++ ++++
Tissue tropism - determinants
Limited or pantropic
- Cell receptors - HIV/CD4+
- Cellular proteins that regulate viral transcription - JC/viral enhancers in oligodendrocytes
- Cell proteases - flu/serine protease
What makes virus virulent
Viral genes affecting virulence
- Those that affect the ability of virus to replicate
- Those that modify host’s defense mechanisms (eg. virokines/viroreceptors)
- Those that enable virus to spread
- Those that have intrinsic cell killing effects
How do cytolytic viruses injure cells
- Inhibition of host protein and RNA synthesis - leads to loss of membrane integrity
- Syncytium formation
- Induction of apoptosis
How do non-cytolytic viruses injure cells
- CD8+ mediated
- CD4+ mediated
- B cell mediated
How else can viruses injure cells
- Cell injury associated with free radicals
Routes of viral transmission
- Skin/mucous membrane
- Respiratory tract
- Faecal oral
- Blood borne
- Sexual transmission
- Vertical transmission
Skin/mucous membrane examples
- HSV-1/2
- VZV
Resp tract examples
- Influenza
- Parainfluenza
- RSV
Faecal oral examples
- HAV
- Norovirus
Blood borne examples
- HIV
- HBV
- HCV
Sexual transmission examples
- HIV
- HSV-1/2
Vertical transmission examples
Mother to baby - eg HIV, CMV
- antenatal eg. transplacental
- Perinatal
- Postnatal - eg. breast milk
Effects of rubella infection during 1st trimester
- Congenital infection syndrome
- Cataracts, heart defects, micro-cephaly, mental retardation, deafness
Types of infection
- Acute
- Persistent
- Latent, reactivating infection (continuous replication, latency - restricted viral gene expression)
- Slow virus infection
Acute infection examples
- Rhinovirus
- Rotavirus
- Influenza virus
Persistent infection example
- Lymphocytic choriomeningitis virus
Latent, reactivating infection example
- Herpes simplex virus
Slow virus infection examples
- Measles virus SSPE
- Human immunodeficiency virus
What is SSPE
- Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder of children and young adults that affects the central nervous system (CNS). It is a slow, but persistent, viral infection caused by defective measles virus
Features of latent infection
- DNA viruses or retroviruses
- Persistence of viral DNA (extra-chromosomal element - herpes viruses or integrated within the host genome - retroviruses)
- During cell growth, viral genome is replicated along with the host cell chromosomes
Herpes simplex virus reactivation presentation
- Fever
- Blisters or cold sores
What might retrovirus infection result in
- Transformation of the cell leading to cancer
Host response against acute infection
- Establishment of infection
- Induction of adaptive response
- Adaptive response
- Memory
Control of acute vs chronic infection
Acute infection - non equilibrium process (host response and virus infection change continually until resolution)
Chronic - equilibrium between virus and host - balance until equilibrium changes
How do viruses evade immune system
- Inhibition of antigenic processing
- Production of cytokine receptor homologues
- Production of immunosuppressive cytokine
- Infection of immunocompetent cells - HIV
Inhibition of antigenic processing - mechanism
- Blockage of transporter associated with antigen processing - HSV
- Removal of MHC-1 molecules from endoplasmic reticulum - CMV
Production of cytokine receptor homologues - mechanism
- IL-1, IFN-gamma - Pox viruses, vaccinia
- Chemokine - CMV
Production of immunosuppressive cytokine - mechanism
- IL-10 - EBV
How do influenza viruses evade host defense mechanisms
- The virus can change its surface antigens - the immune response no longer able to identify them
- Mechanisms of antigenic variation HA and NA - antigenic drift and shift
Antigenic shift
Antigenic shift is the process by which two or more different strains of a virus, or strain of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains.
Antigenic drift
Antigenic drift is a mechanism for variation in viruses that involves the accumulation of mutations within the genes that code for antibody-binding sites
