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Biosci 764 > Module 2 > Flashcards

Module 2 Flashcards

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1
Q

Factors that contribute to potential zoonoses and emerging diseases

A
  • intensified livestock
  • illegal and poorly regulated wildlife trade
  • climate change
  • deforestation
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2
Q

What contributes to zoonotic potential

A
  • exposure = likelihood of contact and infection with a zoonotic agent
  • Reservoir host
  • Spillover
  • Vector
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3
Q

Mechanisms of viral transmission

A
  • Zoonotic
  • Vector borne
  • Blood borne
  • Direct contact
  • Fomite
  • Faecal-oral
  • Vertical/congenital
  • Droplet/airborne
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4
Q

Example of a zoonotic viral transmission

A

Hepatitis E virus:
- ssRNA+
- major cause of acute liver disease
- usually self-limiting but chronic if immunocompromised
- no specific antivirals available but treatment success is highly variable
- emerged from an ancient recombination event between a plant virus and a animal virus
- mode of transmission depends on genotype (3,4 and 7 are zoonotic)
- swine are a major reservoir

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5
Q

Blood-borne viral transmission

A
  • infected body fluid enters blood stream of another person via sexual intercourse, needles, blood transfusions etc
  • healthcare and prison workers are at high risk
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6
Q

Blood-borne viral transmission example

A

Hepatitis C
- enveloped, ssRNA+
- antiviral targets the cleavage process of viral translation
- most common reason for liver transplant and liver cancer
- Classified into 7 genotypes with 1 being the most prevalent
- transmission =parenteral and blood-to-blood mainly
- egypt has endemic prevalence due to a mishap with unclean needles during a vaccination

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7
Q

Clinical phases of HCV

A
  • preicteric = liver enlargement causing right quadrant pain, nausea and lethargy
  • Iceteric = billuria, pale stools and jaundice
  • convalescent
  • chronic
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8
Q

Vector-borne viral transmission

A
  • Transmitted via arthropod vectors often when taking blood meals
  • aka arboviruses
  • majority have RNA genome prone to genetic modifications driving new habitats, hosts and novel viruses
  • Aedes spp. of mosquito are responsible for dengue virus, yellow fever virus and zika virus
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9
Q

Factors affecting Aedes spp. mosquitoes

A
  • tropical regions help with larval maturation
  • warmer weather is associated with shorter insect generation times and increased biting activity
  • increased risk with increasing temperature and rainfall
  • global warming could increase risk
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10
Q

Vector-borne viral transmission example

A

Zika virus
- Enveloped ssRNA+
- Often asymptomatic but can cause fever, red eyes, joint pain, headache, rash
- can cause newborn microcephaly if the mother is infected
- currently no vaccine
- treatment can increase the severity of dengue virus as they are in the same universe
- can be sexually transmitted and via blood transfusions
- found in multiple genera of mosquitoes
- main reservoir species not yet identified
- antibodies detects in species such as sheep, goats and horses

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11
Q

Direct contact viral transmission

A
  • easy transmission so often very high seroprevalence by adulthood as they have had it as children
  • includes touching, kissing, sexual contact, or contact with bodily fluids like blood, saliva, or respiratory secretions
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12
Q

Direct contact viral transmission example

A

Epstein-barr virus
- Enveloped, dsDNA
- 2 types distinguished by differences in the TF EBNA-2 that is essential for B-cell transformation
- usually acute infection but can become chronic
- primarily transmitted via saliva but can also be via sexual contact
- often asymptomatic
- major risk factor for MS - EBV protein mimics protein in the brain and spinal cord which triggers autoimmunity against nerve cells causing MS
- associated with several cancers by cause mutations or severe disease
- seroprevalence increases with age

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13
Q

Direct contact viral transmission - sexual contact example

A

HIV
- Lentivirus transmitted as +ssRNA enveloped virus, then integrates into host genome
- has evolved to enter immune cells = macrophages, microglial cells, CD4+ T cells
- mostly transmitted sexually
- enters cells via interaction of virion envelope glycoproteins on the target cell membrane
- leads to rapid T cell depletion causing the immune system to collapse
- no current vaccines, have to be on antivirals for life

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14
Q

Fomite viral transmission

A
  • inanimate objects that can carry and spread infectious diseases
  • transmitted via people sneezing/coughing onto surfaces or from flushing toilets via air onto surfaces
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15
Q

What does fomite transmission depend on

A
  • type of virus
  • infectious dose
  • room temperature = changes structure of envelope
  • humidity = changes structure of envelope
  • fomite porosity
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16
Q

Fomite viral transmission example

A

Enterovirus 71
- Agent of hand, foot and mouth disease
- transmission occurs via close personal contact, droplet infection via sneezing, faecal oral and contact with contaminated fomities
- high seroprevalence
- no anti-virals

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17
Q

Faecal-oral transmission

A
  • waterborne/foodborne diseases
  • 1/3 of food poisoning in developed nations
  • mostly cause gastroenteritis or hepatitis
  • transmission can be via poor hygiene, contaminated drinking water/food, sewage contaminated water run off onto crops
  • must be resistant to the pH of the GI in humans thus are usually naked
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18
Q

Faecal oral transmission example

A

Norovirus
- usually self-limited disease transmitted person-person and faecal contaminated food/water
- symptoms = diarrhoea, vomiting, nausea
- no anti-virals or vaccine
- chronic in immnocompromised
- predominant agent of acute gastroenteritis
- very contagious, low infectious dose, environmentally resistant
- causes periodic pandemics due to recombination to enable evasion of herd immunity

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19
Q

Vertical/congenital viral transmission

A
  • infection may occur during gestation, childbirth, breastfeeding, can be passed from germline to zygote via chromosomal integration
  • can cause foetal malformation and pregnancy complications
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20
Q

Vertical/congenital viral transmission example

A

Human Cytomegalovirus (HCMV)
- enveloped, dsDNA
- often asymptomatic in healthy individuals
- life-threatening for immunocompromised and infants
- Transmission = body fluids, blood transfusions, sexual transmission, infection across placental barrier
- remains latent for life
- most common virus to be passed to developing foetus
- causes deafness, learning and intellectual disabilities in young

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21
Q

Droplet/airborne viral transmission

A
  • spread via coughing, sneezing or talking
  • airborne = microbes travel within aersolised droplets <5um
  • droplet = microbes expelled in larger droplets >5um
  • more viral RNA can be contained in fine aerosol particles than coarse aerosols
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22
Q

Droplet/airborne viral transmission example

A

Measles
- enveloped, non-segmented negative strand RNA
- highly contagious
- low infectious dose
- 10-14 day incubation period
- causes transient but profound immunosuppression = increased susceptibility to secondary bacterial and viral infections
- immunomodulatory =alters interferon pathways
- vaccine-preventable

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23
Q

Viral peak seasons for transmission

A
  • seasonal variation in temperature and rainfall can change peak seasons = dengue peaks in rainy seasons
  • can depend on virus mode of transmission
  • depends on host variations such as low Vit D can increase susceptibility to SARS-CoV-2
  • models suggest small seasonal changes in host or pathogen factors are sufficient to create large seasonal outbreaks which could be amplified by climate change
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24
Q

How viruses affect distinct populations

A
  • Previous exposure
  • Host genetic variants
  • environment
  • interactions
  • behaviours
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25
Viral host factors
- sex hormones = females have a greater immune response - age - immune status - exposure - behaviour - socio-economic disadvantage - overcrowded housing - underlying health issues
26
Genetic influences to viral transmission
- ethnic-specific genetic SNPs - admixture - introgression - viral co-evolution - ACE2 and TMPRSS2 affect SARS-CoV-2 entry - CCR5 prevents HIV infection - FUT2 affects susceptibility to norovirus infection as it is an enzyme involved in protective mucosal functions
27
SARS-CoV-2 affect on ethnic minority groups
- higher rate of infection and severity - 2x more likely to need hospital care - make up a large amount of healthcare workers, intergenerational housing, inaccessibility to healthcare, underlying health issues and genetics
28
How are genetic influences deteced
GWAS which scans for genetic markers associated with disease/severity
29
Limitations of GWAS
- only obvious with large phenotypic effect - cannot detect small effects - hard to detect complex traits
30
Epidemic
disease that affects many people in a region
31
Pandemic
epidemic that is spread over the globe
32
Endemic
constant presence in a specific location
33
Spanish flu
- 1989-1919 H1N1 influenza A pandemic - virulent novel strain unusually severe in young adults due to cytokine storming - mortality rates exacerbated by malnutrition, poor hygeine, end of WWI and severe climate anomaly - found rapid viral replication when genomes sequenced from autopsy tissues - samoa quarantine period prevented deaths until lifted = shows the importance of quarantines
34
HIV
- 1980s pandemic - likely prevalent prior to the 1980s but went undetected - first antiviral approved 1987
35
Chiu et al 2022 paper - climate change on norovirus transmission
- clinical stool samples taken from an outbreak in Taiwan - GII.6 genotype had higher proportion in summer while other GII genotypes were mostly in winter and spring - Different GII subtypes differentially affected age groups = GII.7 had higher median age (maybe due to behavioural differences) while GII.3 had a lower median age (more often in kids due to adaptive immunity) - as temperature decreased then prevalence increased - less associated with humidity than rainfall - increased rainfall = increased pathogen spread - norovirus will likely be altered by climate change and increasing population density
36
Kim et al 2024 - H5N1 global epidemiology in wild birds in South Korea
- Collected swabs of captured birds, carcasses of birds and fecal samples = screened using rRT-PCR - most transmitted via carcasses in north and south of south korea - wild birds jumping from europe to central asia mostly - There was frequent transmission from wild birds to poultry farms - highest time spent by virus in each host was highest in wild birds= suggests wild birds play a vital role in spread and maintenance of clade 2.3.4.4b - clade 2.3.4.4 viruses caused longer outbreaks than previous outbreaks - large amount of reassortment occurring - now seeing spillover into domestic animals = concerning due to biological similarities with humans - limitations = sampling frequency, subsampling may introduce bias, each nation has its own survelliance system, doesnt include North Amercica
37
Techniques for studying viruses
- structural biology = cryo-EM and X-ray crystallography - sequencing of viral genomes - culture - OPCR - Epidemiology
38
Cryo-EM microscopy
- study structure for classification identify antiviral targets and understand host binding - virus prepared by embedding in vitreous ice then visualised under high power microscope using electron beams - small proteins are difficult
39
X-ray crystallography
- study structure of virus for drug-binding and modelling structure - prepare a crystal with virus embedded and determine structure via X-ray beam - diffraction off the crystal to build 3D picture of electron density and atomic positions
40
Sequencing of viral genomes
- next gen, third gen, metagenomics and real time sequencing - can be used for predictive modelling, phylogenetics, identification of virus via homology and structure prediction - can detect more viruses in enviro sample to avoid bias of what can be cultured
41
Culturing viruses
- required to understand molecular mechanisms - can text anti-virals - Plaque assay = determines infectious dose based on plaque formed - foci forming assay = detects clusters via using probe antibodies
42
Culturing viruses limitations
- need cell type which is permissive (virus can enter) - need to cause cytotoxic effects - large amounts of viruses cannot be controlled
43
OPCR
- quantify viral load in samples - gives baseline before and after treatment comparison
44
Epidemiology
study patterns of infection what is driving transmission and what becomes the predominant strain
45
Respiratory syncytial virus (RSV) transmissibility determined by
- infectivity of the pathogen - contagiousness of infected individual
46
RSV host determinants
- tissue and cellular tropism - receptor expression - viral shedding - what phase of the infection you are in - lung function - pre-existing immunity or vaccination - social contact patterns - age-related mixing patterns - genetic variation
47
RSV inter-host factors
- virus stability - respiratory droplet size and deposition - airflow and recirculation
48
RSV host factors
- mucocilliary clearance efficiency - seasonal nutritional deficiencies - respiratory secretion production and viscosity
49
RSV viral determinants
- viral envelope and capsid = more susceptible to environmental changes - genome = how quickly it evolves to escape host immunity - replication rates - receptor specificity = more specific = less likely to catch virus
50
RSV environmental determinants
- temp - rainfall - pH - humidity - salinity - surface materials - UV - ventilation and airflow - season
51
Secondary attack rate
proportion of infected among susceptible in contact with primary case
52
Basic reproduction number
average number of successful transmissions per infectious individuals in a population
53
Non-pharmaceutical RSV interventions
- masks - hand hygiene - surface cleaning - air ventilation
54
pharmaceutical RSV interventions
- vaccines - antivirals - prophylactic treatment
55
Herd immunity
vaccination of atleast 95% of the population to prevent the transmission of the virus to the vulnerable population
56
Baldauf et al 2022 - CRISPRi links COVID-19 GWAS loci to LZTFL1 and RAVER1
- investigates how SNPs influence COVID-19 severity - used CRISPRi to repress regions near SNPs - LZTFL1 regulated airway cilia function, reduced expression impairs viral clearance = higher risk of severe COVID in individuals with risk alleles -RAVER1 is significantly decreased in COVID-19 severity - RAVER1 coactivates MDA5 which is a key signalling factor in the antiviral pathway = MDA5 senses dsRNA and initiates IFN, RAVER1 increases affinity of MDA5 for dsRNA - reduced RAVER1 expression weakens immune response - ICAM1 gene is suppressed in severe human cases but is elevated in resistant monkeys - kids have elevated MDA5 pathway genes making them less susceptible to COVID
57
Ruche et al 2009 - The 2009 Pandemic H1N1 Influenza and Indigenous Populations
- examines disproportionate H1N1 impact on indigenous populations - higher hospitalisation and mortality rates in indigenous populations when compared to non-indigenous - higher prevalence of risk factors in indigenous populations = diabetes, obesity, asthma, pregnancy, deprivation and susceptible HLA genotypes - recommendations to have targeted vaccination for indigenous groups and improved surveillance - limitations = nations collected data in different ways, small case numbers, number of factors not taken into account
58
Betts et al 2023 -Influenza-Associated Hospitalisation and Mortality Rates Among Global Indigenous Populations
- meta-analysis of influenza severity in indigenous populations - highest hospitalisation rate in Canada and AUS/NZ - pandemic H1N1 had greater effect than the seasonal flu - underlying causes = socioeconomic disparities, comorbidities and healthcare barriers - urgent need for prioritised vaccination and pandemic planning for indigenous communities
59
RSV ovrview
- droplet and aerosol transmission - ssRNA - transmission peaks over colder months as virus remains intact - high reinfection rates - average person shed RSV for 11 days post infection but immunocompromised can shed for m,onths - major cause of pneumonia and bronchiolitis - risk factors = male, birth during or prior to RSV circulation, low birth weight, underlying comorbidity - no specific antivirals
60
RSV prevention
- Synagis = month infection of a monoclonal antibody which recognises pre-fusion f protein - Vaccine for high-risk older groups - Nirsevimab = monoclonal antibody which recognises pre-fusion f protein but has higher efficacy than synagiis
61
Why has it taken so long to develop a paediatric RSV vaccine
- maternally-derived antibodies suppress induction of RSV-specific immunity - lack of durable protective immunity induced by natural infection - 1st vaccine developed made the disease worse - very young babies are hard to study - RSV evades host immunity and elicits poor antibody responses
62
Enviro factors impacting RSV
- higher rainfall = higher risk - tobacco exposure - crowded living conditions - air pollution - low temp and humidity = survival rate increased
63
Host factors impacting RSV
- age = babies and old - pre-term birth and low birth weight - siblings that attend school - malnutrition = Vit D and A deficiencies - Male - indigenous - comorbidities - genetics
64
Viral factors RSV
- co-infections with HMPV and human rhinovirus - RSV proteins - NS1 and NS2 block IFN signalling and downregulate cell apoptosis, G proteins bind antibodies - viral load - strain - isolate

Biosci 764 (6 decks)

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