11 - Acute Viral Infections Flashcards
Patterns of viral infection
- Acute
- Latent
- Persistent asymptomatic
- Persistent pathogenic
Example of acute virus
- Rhinovirus
- Rotavirus
- Influenza
example of latent virus
HSV
Example of persistent asymptomatic virus
- Lymphocytic choriomeningitis virus
- JC virus
Example of persistent pathogenic virus
- HIV
- Human T lymphotropic virus
- Measles
Acute viral infections
- Rapid and self limiting
- Rapid onset of infectious virions, followed by resolution and elimination of of the infection by the host (‘clearance”)
- Only occur when intrinsic and innate immune responses are transiently bypassed
Acute infections present in common public health problems
- Often associated with serious epidemics affecting millions of people
- Infected host often infectious before symptoms manifest
- Difficult to control as by the time host is sick enough to stay home, transmission has already occured
Measles
- Enveloped
- Family Paramyxoviridae
- (-) sense ssRNA, non segmented genome
- Highly contagious disease transmitted by respiratory aerosols that triggers a temporary but severe immunosuppression
Symptoms of measles
- Fever
- Cough
- Conjunctivitis
- Maculopapular, erythematous rash
Complications of measles
- Encephalitis
- Ear infection
- Pneumonia
- Diarrhoea
Pathogenesis of measles
- Infects alveolar macrophages and memory T and B cells
- Clearance of MV infected cells requires destruction of these immune cells
- Result is immunosuppression followed by loss of memory to other pathogens
What can maculopapular skin rash lead to
Severe desquamation
MeV infection and lymphocytes
- Suppresses the proliferation of lymphocytes
- Lymphocytes isolated from patients proliferate poorly upon ex vivo stimulation
Immune evasion by MeV (SSPE)
By cell to cell spread in neurons
Cell to cell spread of MEV in neurons
- Mediated by microfusion events at cell membrane where F proteins bind neurokinin-1 receptors (facilitates membrane fusion)
- Viral RNP complexes accumulate at cell membrane and pass through
What prevents antibody detection of free Mev virus in neurons, thus promotes latency in brain
In neurons there is incomplete assembly of virus particles at the membrane and budding of virus does not occur
What is the most contagious infectious disease known
Measles
SARS-CoV-2
- Linear (+) ssRNA genome
- Family Coronaviridae
R0 value
Refers to the contagiousness and transmissibility of infectious pathogens
R0 value of SARS-CoV-2
- 4.9
- Twice as transmissible as influenza
Viral dissemination into body organs
- Initial replication takes place in upper respiratory tract, followed by migration of virus to lungs
- Primary viremia occurs after establishment of infection and replication in lung pneumocytes
- This viremia disseminates the virus throughout the body via blood stream where another cycle of viral replication takes place, thus leading to further dissemination
Respiratory Syncytial Virus
- Orthopneumovirus (group 5)
- (-)ssRNA, non segmented
- Filamentous, enveloped virion
- Close contact and aerosol transmission
- Infects nearly all children by 2 years of age
- ~60,000 deaths p.a under <5yo
RSV initial replication
In nasopharynx and upper respiratory tract and may spread to small bronchioles or alveoli of lower resipratory tract
RSV infection of epithelial cells
- Elicits widespread transcriptomic and proteomic changes, which both mediate the host immune responses
- RSV can circumvent the host stress responses, including apoptosis
- Result is to severely impact human lungs, resulting in airway remodeling and pathophysiology.
Antigenic groups of RSV
GRoups A and B
Anti-RSV antigenicity and immunity
- Neutralising antibodies to F and G proteins develop soon after infection with RSV groups A and B
- Duration of immunity is short-lived (re-infection upon challenge with the heterologous subtype occurs within 2 months)
- Within 26 months 73% experience two or more, and 47% experience three or more infections
RSV pathogenesis
- Restricted to superficial cells of respiratory epithelium
- Giant cells with round, pink intracytoplasmic inclusions seen in tissues
- Tropism largely limited to humans (transmission
between animals and in populations does not
occur - semi-permissive) - However, infection of and transmission among chimpanzees is sustained
Cells infected by RSV
Cells from trachea, bronchi, and bronchioles
Viral factors of RSV
- G protein
- F protein
- NS1 and NS2
- Viral strains and isolates
- Viral load
G protein
Glycosylation, sG neutralising antibodies avoidance
F protein
Conformational change, infectivity and protection
NS1 and NS2
IFN-1 inhibition
Host factors of RSV
- Male
- Lung and heart anomalies
- Low vit D level
- Inadequate immune system
- ?Genetic polymorphism
Environmental factors of RSV
- Exposure to smoke
- Air pollution
- Winter
Patients who develop severe RSV infections
Undergo exaggerated cell mediated immune response (e.g. increased granzyme B and cytokine release) and/or improper immune regulation
Hemophagocytic lymphohistiocytosis
(HLH)
Fail to undergo normal immune contraction and require immunosuppression to prevent death
Dengue virus genus and family
Orthoflavivirus genus of Flaviviridae family
Mosquito that carries dengue
Aedes aegypti infected by feeding on a person in viraemic phase of infection
Dengue lifecycle
- During the extrinsic phase of the cycle, dengue viruses first infect mosquito midgut cells and other tissues before
disseminating to the salivary glands - An infected mosquito can then transmit the dengue virus to several humans as it
feeds or attempts to feed - Once infected, it takes an average of 4–7 days for the onset of symptoms and for a
person to become capable of transmitting dengue virus to a new mosquito - Both symptomatic and asymptomatic individuals can transmit dengue virus to mosquitoes
Four distinct dengue viruses
DENV 1-4
Dengue Virus
- Linear (+) ssRNA genome (group 4)
- Each serotype includes several genotypes
- Infection with one serotype is confers lifelong immunity to that serotype but not to the other three serotypes
- People who live in dengue endemic areas can be infected up to four times
in their lifetimes - Re-infection (with a different serotype) is associated with more severe disease
What is clearance of DENV antigens and genome associated with
Development of adaptive immune response
Diagnosis of DENV
- Non-structural 1 (NS1) antigen and antibodies change over time
- Thus different diagnostic tests will be appropriate depending on the stage of infection (e.g. ELISA, RT)
Levels of IgM and IgG in primary dengue infection
IgM peaks first then IgG
Levels of IgM and IgG in secondary dengue infection
IgG peaks first and much higher then IgM
Factors involved in control of dengue
- Immune status
- Viral strain
- Genetic status
- Age
