Lecture 18 - Influenza SARS-CoV-2 Flashcards
What is the name of the family of Influenza viruses?
Orthomyxoviridae
What are some viruses part of the Herpesviridae family?
Herpes
EBV
Varicella zoster
What type of genetic material does Orthomyxoviridae have?
ssRNA
-ve sense
What type of genetic material does the Coronarviridae specifically SARS-CoV-2 have?
ssRNA
+ve sense
What area of the body does influenza/flu affect?
Acute viral infection of respiratory tract
How infectious is influenza (relatively)?
Can people with mild or no symptoms transmit influenza?
Highly infectious
Even with mild or no symptoms, people with influenza can infect others
What are the shapes of orthomyxoviruses?
Spherical
Segmented negative single stranded RNA
What is the important viral enzyme that is important in the replication of the orthomyxoviruses which leads to them having high mutation rates?
Viral RNA polymerase
Why does presence of viral RNA polymerase lead to high levels of mutations in Orthomyxoviridae?
Viral RNA polymerase = high error rate
High error rate because RNA polymerase has no proof reading like DNA polymerase which leads to mutations
What are the 2 main surface antigens for Orthomyxoviridae?
Haemagglutinin (H)
Neuraminidase (N)
What is the function of the H surface antigen (Haemagglutinin) on Orthomyxoviridae?
Binds to the surface receptor on host cells starting the process for the virus to enter the host cell
What is the function of neuraminidase surface antigen (N) on the orthomyxoviruses?
Allows the virus to move away from the cell
What are the 3 types of influenza viruses seen in humans?
Influenza A
Influenza B
Influenza C
What is the order of severity of the 3 Influenza viruses seen in humans?
From most severe to least severe:
Influenza A (most severe)
Influenza B
Influenza C (least severe)
Which of the 3 strains of influenza has the most potential host organisms and what are a few examples?
Influenza A
Humans
Swine
Equine
Birds
Marine
Mammals
Which strain of influenza has only human hosts?
Influenza B
Which of the influenzas has both Antigenic shift + Antigenic drift?
Influenza A
What influenzas only have Antigenic drift (NOT antigenic shift)?
Influenza B
Influenza C
Which influenza is a mild disease WITHOUT seasonality?
Influenza C
Which influenza can cause large pandemics with significant mortality in young persons?
Influenza A
Which influenza can cause severe diseases which is generally confined to older adults or persons at high risk where pandemics are not normally seen?
Influenza B
What is the main animal reservoir for Influezna A viruses?
Birds (mainly wildfowl)
Which Influenza virus is the main cause of outbreaks, epidemics and pandemics?
Which Influenza virus causes less severe disease and smaller outbreaks?
Influenza A
Influenza B
Which group of people does Influenza B normally affect?
Children
Older adults
Immunocompromised
How does influenza replicate (not an ILO)?
-ve ssRNA converted to +ve ssRNA
+ve ssRNA translated back to -ve ssRNA by RNA polymerase to be packaged
What route is Influenza transmitted?
Via the respiratory route (coughing, sneezing and inhaling)
What are the 3 potential modes of transmission of influenza?
Small particle aerosols suspended in air
Larger particle or droplets on ground near infected person (direct contact)
Virus particles on surfaces where the influenza remains infectious (indirect contact)
What are the 3 types of innate barriers to the entry of influenza via the respiratory route?
Respiratory epithelial cells covered in thick glycocalyx and tracheobronchial mucus
Ciliated epithelial cells sweep mucus up from lower respiratory tract (mucocillary escalator)
Secretion of IgA, Natural killer cells and macrophages in the lungs
What type of residue does the influenza virus bind to on the glycoprotein/glycolipid receptor for the influenza virus?
Neu5Ac residue which is a Sialic acid
How does the Influenza virus actually enter the cell?
Haemagglutinin protein on virus surface binds to sialic acid Neu5Ac residues on the receptor
Receptor mediated endocytosis takes in the virus
How does the virus leave the cell?
The Neuraminidase cleaves the connection between the viruses Haemagglutinin and the glycoprotien/sialic acid receptor residue so its released
What are some symptoms of Influenza?
Fever
Fatigue
Headache
Sore throat
Cough
Aches (myalgia)
Nausea
Vomiting
Diarrhoea
Many more potential symptoms
What are some complications of influenza that are more common in children?
Febrile convulsions
Reye’s syndrome
Otitis media
Croup
What is the average incubation period of influenza A?
Between 1-5 days
Average 2-3 days
Who are at risk of most serious complications of influenza?
Children under 6months
Elderly
Underlying conditions like respiratory disease
cardiac disease,
immunosuppressive,
long term neurological conditions
Pregnant
Morbidly obese
How long does it normally take for someone to recover from influenza?
About 7 days
How is influenza usually diagnosed?
By symptoms and clinical assessment
Rapid antigen tests
Influenza PCRs
What are the 2 types of drugs that can be used to treat influenza?
Antivirals
Neuraminidase inhibitors
What are 2 antivirals used to treat influenza?
Which influenza can these treat?
Rimantadine
Amantadine
Only works for Influenza A
How do antivirals work to treat influenza? (Rimantadine and amantadine)
Inhibit viral uncoating after uptake
What are 2 examples of Neuraminidase Inhibitors that can treat influenza?
Oseltamivir
Zanamivir
How do Neuraminidase inhibitors (Oseltamivir + Zanamivir) work to treat Influenza?
Which Influenzas do these work against?
Prevent the virus releasing from the infected cell
Influenza A and B
What is the main treatment against influenza?
Prevention = vaccination (vulnerable groups)
What are the 2 types of of Vaccination for influenza and who are their target groups?
Formalin-inactivated vaccine (quadrivalent/trivalent) for Adults
Live attenuated cold adapted vaccine (quadrivalent) for children
What is meant by the influenza vaccines being quadrivalent?
Protects against 4 strains of influenza:
-2 Influenza A strains
-2 Influenza B strains
How are the formalin-inactivated vaccines for influenza administered?
Injection
How are the live attenuated vaccines of influenza for children administered?
Nasal spray
What is meant by the term “cold-adapted vaccine” for the influenza vaccine administered to kids?
Attenuated influenzae virus can only survive in the cold environment in the child’s nose
Any warmer conditions like deeper in the body it will die
What is the approximate life cycle of influenza A?
6hrs
What is Antigenic drift?
Minor changes/natural mutations in the genes of flu viruses that occur gradually over time (this causes seasonal epidemics
What mutates as a result of the high error rate of viral RNA polymerase in Influenza viruses leading to Antigenic Drift?
Surface antigens:
-Haemagglutinin (H)
-neuraminidase (N)
This can lead to resistance
Does the viral subtype change as a result of Antigenic drift?
No
Only minor antigenic changes in H and N proteins occur
How does WHO decide which influenza strains should be vaccinated against each year?
Follows the virus epidemiolog/antigenic drift of the mutations of the H and N proteins of the virus
Which Influenza virus can have infrequently have dramatic changes in the antigenic properties of H and/or N proteins?
Influenza A
Which type of influenza can show Antigenic Shift?
Influenza A
What is antigenic shift?
When theres a dramatic change in the H and/or N proteins
The H and N surface antigens come from different species
Major changes in the genes of flu viruses that occur suddenly when 2 or more different strains combine. This results in NEW SUBTYPE causing widespread epidemics/pandemics
How does Antigenic shift occur?
Major changes in H and N proteins occurring due to several species of influenza viruses being in the same host
This causes the viral subtype to change
Happens due to reassortment of different RNA segments from each species
How does reassortment of Influenza A occur?
When multiple Influenza A species infect a single host
The mRNAs encoding the H and N antigens get reassorted into unique combinations
Why is antigenic shift occurring in Influenza A dangerous?
New subtype develops
Peoples immune systems dont have defence against new subtype
Causing epidemics and pandemics
What is an Epidemic?
A widespread occurrence of an infectious disease in a community at a particular time
What is a pandemic?
Epidemic over a very large area, affecting a large proportion of a population - often the world
What causes the symptoms of flu?
Body’s immune response to viral infection
Antibodies triggered and immune cells move to site of infection
Release of cytokines leads to local inflammation
How does flu actually kill people?
Immune system overreacts (T cells attack + destroy cells with the virus in like in the lungs)
Opportunistic secondary infection like Streptococcus or staphylococcus in lungs
What does SARS-CoV-2 stand for?
Severe Acute Respiratory Syndrome Coronavirus 2
What is the lay term for SARS-CoV-2?
COVID-19
Which part of the body does SARS-CoV-2 affect (COVID-19)?
Acute viral infection of respiratory tract
How infectious is COVID-19?
Can people with mild or no symptoms infect others?
Highly infectious
Yes can infect others
What is the genetic material of Coronaviridae?
+ve sense ssRNA
What is the general structure of Coronaviridae?
+ve ssRNA with spike proteins projecting from their surfaces
What is the function of the major Spike glycoprotein surface antigen of Coronaviridae?
Needed for entry into cells
What protein does SARS-CoV-1 bind to in the lungs?
ACE2 protein
What organism did zoonotic transfer of SARS-CoV-1 to humans happen from?
Civets to humans
What protein does MERS (Middle East Respiratory Syndrome) bind to?
DDP4
What organism did zoonotic transfer of MERS to humans happen from?
Camels
What protein does SARS-CoV-2 bind to?
ACE2
What organism did zoonotic transfer of SARS-CoV-2 to humans happen from?
Likely bats
What are the animal reservoirs for the Coronaviridae family?
SARS-CoV-1 = Bats —> Civets
MERS = Bats —> Camels
SARS-CoV-2/COVID-19 = Bats —> Unknown
How does SARS-CoV-2 (COVID-19) enter cells?
Spike glycoprotein on vision binds to ACE2 receptor in lungs, heart, kidney and GI tissue
Receptor mediated endocytosis of virus into cells
How is COVID-19 diagnosed?
Lateral flow test
PCR
What is the significance of a positive lateral flow test for COVID-19?
Surface proteins of COVID-19 detected indicating individual is infectious
What is the significance of a COVID-19 PCR being positive?
Detects the viral RNA which can be present for weeks after a person is no longer infectious
So a +ve PCR does not always mean infectious
Why do we get variants in Corona viruses? (Similar to influenza)
Viral RNA polymerase has a high error rate (lack of proof reading)
Leads to mutations
What is the approximate life cycle of a coronavirus?
10hrs
What are the 3 methods of transmission of COVID-19?
Via respiratory tract
Small droplets (inhaled)
Large droplets (over short distances)
Larger droplets settle on surface, person touches it and touches the self
What type of vaccine is used for COVID-19?
Nucleic acid vaccine
How does the Nucleic acid vaccine for SARS-CoV-2 work?
Segment of SARS-CoV-2 viruses genetic material in vaccine
Hosts body uses it to make the SARS-CoV-2 protein which it recognises and triggers an immune response