8- Mechanisms of Viral Infection and Pathogenesis

Question 1

name the three patterns of viral infection

Answer 1

acute infection
latent infection
chronic/persistent infection

Question 2

describe the pattern of acute infection

Answer 2

virus invades and replicates within host, causing a rapid onset of symptoms

stimulates a fast and aggressive immune response that clears the virus and resolves symptoms within a short duration

Question 3

example of an acute infection

Answer 3

flu
measles
smallpox

Question 4

describe the pattern of latent infection - give examples

Answer 4

initial acute infection with symptoms, virus then persists in host by remaining in a dormant/latent state with a low level/ no replication

periodic reactivation with symptoms - triggered by things like another infection, stress or immunosuppression

Question 5

examples of a latent infection

Answer 5

herpes simplex virus
EBV - Epstein-Barr virus
VZV - Varicella Zoster virus

Question 6

how do HSV (herpes) and VZV (Varicella Zoster) display latency as latent viral infections

Answer 6

HSV = at the end of its infectious cycle, it uses retrograde axonal transport to migrate and establish a latent pattern of expression in dorsal root ganglion

during periods of reactivation caused by transient immunosuppression, HSV travels back down nerves and causes cold sores

VZV = initial acute infection known as chickenpox, then uses retrograde axonal transport to establish latency in different ganglions

periods of reactivation are called shingles = manifests as a rash confined to a particular sector of the body (disseminated rash)

Question 7

describe the two patterns of chronic/persistent infection - give examples for each

Answer 7

1. virus infects the host = causes early symptoms initially controlled by the immune system

host immune system then controls viral replication whilst the virus evades immune detection and persists in the host

if the immune system loses control of the virus, it re-emerges

e.g. hepatitis C, HIV

2. host is infected with the virus early on but asymptomatic – the virus remains in the host, isn’t detected or resolved

emerges near end of life with rapid viral replication and symptoms, contributes to death. the immune system here hasn’t controlled the virus, it’s just persisted/been latent and evaded immune detection

e.g. rubella

Question 8

describe congenital rubella syndrome as a persistent infection

Answer 8

a pregnant woman may contract the virus, which is transmitted through the placenta to the foetus in utero

early on in foetal development, the baby won’t have an effective adaptive immune response - this develops later

as T and B cell production is triggered, they’ll recognise the rubella virus as ‘self’ and won’t initiate an immune response against the virus

baby will be born with tissue damage, developmental and congenital abnormalities – sheds the virus for up to 2 years which increases risk of transmission to other children

increased mortality and morbidity risk, the rubella virus will persist in the child, tissue damage and deformities will worsen and the child will die

Question 9

why are inapparent viral infections not necessarily unsuccessful infections?

Answer 9

many viral infections are apathogenic or associated with mild symptoms

this works better for virus survival = allows it to keep host alive and replicate enough to spread to the next host, encourages transmission into the community

symptoms can also change with the strain of virus – from asymptomatic to mild to severe

Question 10

define cytopathic and non-cytopathic damage

Answer 10

cytopathic = virus directly causes damage to host cells, causes cellular dysfunction/ injury/ death

non-cytopathic = virus replicates within host cells without causing overt cellular damage/death; may cause subtle changes to the infected cell function but it’s still functional

Question 11

describe how EBOLA causes cytopathic damage

Answer 11

EBOLA spreads as resp. droplets or by skin contact - targets vascular endothelial cells that line blood vessels

EBOLA infects these cells, completes its life cycle and bursts out of its cell = causes haemorrhagic fever, and blood vessels start leaking

Question 12

describe how influenza A virus causes cytopathic damage

Answer 12

influenza A invades and replicates inside lung epithelia which has ciliated epithelial cells

high level of infection causes ciliated epithelial cells to collapse and clump together

dysfunctional, non-beating cilia means mucus gets trapped in the lungs, as well as fluid = causes resp symptoms like coughing, wheezing, and can develop into pneumonia

Question 13

describe how RSV (respiratory syncytia virus) causes cytopathic damage

Answer 13

RSV infects lung epithelia, fuses together many adjacent cells into one giant, multi-nucleated cells called a syncytia

syncytia is part of the virus’ replication strategy, as it strips off the lungs = causes lung damage, contributed to lifelong atopic asthma in kids and death with significant resp damage

Question 14

what is immunopathology? what are three viruses linked to immunopathology?

Answer 14

immunopathology = immune responses against a virus associated with disease, contributing to damage

viruses - hepatitis C, dengue virus, respiratory syncytia virus/RSV

Question 15

how does hepatitis C virus (HCV) infection lead to chronic liver inflammation and damage?

Answer 15

chronic liver inflammation occurs from the extensive infiltration of leukocytes into liver and high levels of pro-inflammatory cytokines produced

immune response is against the severe liver damage and loss of hepatocytes caused by HCV

Question 16

how does the immune system attempt to resolve and clear HCV infection?

Answer 16

HCV invades and infects hepatocytes - hepatocytes present viral peptides on their surface through MHC class I molecules

T cells recognise peptides as foreign - are activated, identify and attack infected hepatocytes to clear the virus from the liver

however HCV generates viral variants that aren’t recognised by CD8+ T cells - evade immune detection = virus resists elimination, contributes to chronic liver inflammation

Question 17

what is dengue fever? how is it transmitted?

Answer 17

dengue fever- caused by dengue virus, has 4 distinct serotypes

transmitted through mosquito bites as a mosquito-borne infection

Question 18

clinical manifestations of severe dengue?

Answer 18

severe dengue can manifest as dengue shock syndrome (DSS) and haemorrhage

high mortality rate

Question 19

how does previous infection with a different serotype of dengue virus increase the risk of severe clinical manifestations?

Answer 19

antibodies formed against one previously exposed to serotype don’t provide cross-protection/ may worsen infection with another serotype

the second serotype will bind to the antibodies for the first serotype - will be allowed entry into macrophages due to their Fc gamma receptors

macrophages disseminate around the body allowing the virus to spread to different tissues

this can lead to antibody-dependent enhancement (ADE) = cause more severe disease manifestations

Question 20

how does ADE contribute to severe dengue manifestations?

Answer 20

non-neutralizing antibody binds to a different serotype of dengue virus = forms an immune complex

this complex binds complement proteins = triggers a complement cascade that induces inflammation and attracts immune cells to the site of infection

internalization of the complex into mononuclear phagocytes through their Fc receptors worsens the infection - leads to severe dengue symptoms

Question 21

define antibody-dependent enhancement

Answer 21

when pre-existing non-neutralizing antibodies enhance the entry of a virus into target cells = increases infectivity and worsens disease

occurs when antibodies bind to a virus but fail to neutralize it - facilitate viral entry into host cells via Fc receptors on immune cells

Question 22

what is the impact of RSV infections on the immature immune system in early life?

Answer 22

trigger an unbalanced Th2/Th1 immune response, with Th2 predominance over Th1 - infant hasn’t made the switch from Th2 to Th1 response yet

imbalance leads to:
- reduced inflammatory cytokines
- reduced CD8+ T-cell responses and IgG production
- enhanced IgE production

hinders efficient viral clearance and impairs immune memory

Question 23

how does the Th2 predominance in RSV-infected infants contribute to respiratory symptoms?

Answer 23

skewed Th2 response leads to increased production of IgE antibodies

IgE bind to RSV molecules - triggers mast cells and eosinophils to release histamine

causes resp symptoms - respiratory wheezing, asthma-type symptoms, and allergic reactions.

Question 24

what is the difference between Th2 and Th1 responses?

Answer 24

Th1 responses are important for cell-mediated immunity and clearing intracellular pathogens

Th2 responses are for humoral immunity and allergic responses

babies can’t make Th1 responses, rely on Th2 responses until 6-12 months of age when their immune systems make the switch

Question 25

what is the role of immunopathology in RSV infections?

Answer 25

RSV infections cause direct lung tissue damage = leads to resp. symptoms

immunopathology from the unbalanced Th2/Th1 response worsens resp symptoms, contributes to disease severity

Question 26

how does the adaptive immune system impact the severity of infections?

Answer 26

previous immune encounters can help or hinder disease outcomes

vaccines provides lifelong protection = control disease severity by preventing reinfection - e.g. measles

for viruses that constantly change - e.g. influenza - vaccines and immune control are harder to achieve

Question 27

what is an example of a disease controlled by the adaptive immune system through vaccination?

Answer 27

measles

vaccine provides lifelong protection against the virus and prevents reinfection

measles doesn’t alter its surface antigens to evade immunity

Question 28

describe the pathology of influenza

Answer 28

challenging as people of all ages are infected = a more serious problem in the elderly and asthmatic children

symptoms range from mild upper resp tract infections to severe lower resp infections, which can lead to viral pneumonia

prolonged fever, headaches, malaise and myalgia are common symptoms

Question 29

what is antigenic drift in influenza?

Answer 29

antigenic drift = small amino acid sequence changes in the surface protein hemagglutinin of influenza

haemagglutinin is a highly immunogenic surface protein - aids in influenza entering host cells

these changes occur when the virus is under immune pressure - creates a new influenza virus strain that may evade existing immune responses, requires the production of new neutralising antibodies

Question 30

how does antigenic drift impact the effectiveness of flu vaccines?

Answer 30

creates new influenza virus strains = hard for flu vaccines to provide protection against all strains when new ones emerge unpredictably

hemagglutinin sequence changes slightly with each drift = new neutralizing antibodies are needed for each strain

Question 31

what role do neutralizing antibodies and T-cell responses play in influenza immunity?

Answer 31

neutralizing antibodies for previous flu infections may still be effective against new strains - depends on the similarity between the strains

previous T-cell infections can help alleviate symptoms and contribute to immunity against new influenza strains

Question 32

what is antigenic shift in influenza?

Answer 32

antigenic shift = significant changes in the surface proteins of the influenza virus - hemagglutinin and neuraminidase

creates a new strain with enhanced pathogenicity, instigates pandemic flu episodes

Question 33

how does antigenic shift contribute to the emergence of new flu strains?

Answer 33

as influenza virus consists of genes and chromosomes - two flu strains within the same host can undergo reassortment and gene swapping = creates a new flu strain

changes in haemagglutinin and neuraminidase surface proteins define flu serotypes - can impact flu infectivity, pathogenicity and virulence

flu strains are identified by their HN serotypes

Question 34

what factors influence the outcome of a viral infection?

Answer 34

previous exposure history to similar strains

the specific influenza virus strain encountered

state of immune system - elderly and young often more vulnerable

antigenic drift and shift, and the emergence of new strains with varying pathogenicity

luck - can be unlucky with the disease outcome of a virus strain