Lecture 16 - Flu Flashcards
Influenza viruses are members of what virus family?
Orthomyxovirus family
Identify Influenza virus characteristics
- Envelope or No envelope
- Genetic material
- Required enzyme
- Envelope
- (-)ssRNA
- RNA-dependent RNA-polymerases
What must Influenza bring with it for replication of its genetic material to occur?
RNA-dependent RNA-polymerase to provide mRNA for protein production and to replicate the RNA genome
T or F, Influenza virus has a segmented, (-)ssRNA genome which does not have the ability to mutate frequently
False, It does have the ability to mutate frequently
What is significant about the influenza viral genome other than being (-)ssRNA
It is segmented, being found in 8 different pieces associated with 8 separate nucleocapsids within each viral particle.
What does influenza’s segmented genome allow it to do?
It allows for genome mixing when two different influenza strains infect the same cell.
What are the two important spike proteins that are the main target of the adaptive immune response
Neuraminidase (N protein)
Hemagglutinin (H protein)
What happens if N protein and H protein get switched?
Antigenic shift. A virus with a brand new combination of spikes goes on to cause disease as a new strain
What is a pandemic?
Worldwide epidemics
Other than antigenic shift, how else can two spike protein genes be switched?
By a simple mistake during viral genome replication. Such minor point mutations can result in a new amino acid near region of spike protein that interacts with Ab
How does the host immune system respond to influenza viruses?
Antibody immunity to influenza viruses usually involves Abs binding and covering the key spike epitopes, blocking virus spike binding to the host cell and thus neutralizing the virus
What is Antigenic drift and how do viruses avoid the immune system of the host?
Antigenic drift is when a minor point mutation results in a new amino acid at or near the epitope of spike proteins that interact with antibodies. When this epitope is altered, it can prevent antibody from binding but still allow the virus to infect. Subsequent hosts are no longer immune to this new mutant and a new epidemic is on its way!
Make sure to understand the difference between Antigenic Shift and Antigenic Drift
Shift - Proteins are switched during genome mixing of two different influenza strains infect the same cell.
Drift - A viral point mutation occurs at a spike site, disallowing the antibody to bind and neutralize the virus
What is a common feature of viruses that use RNA-dependent RNA-polymerases?
Antigenic drift because of the lack to spell-check which is a feature of DNA-dependent polymerases
When was the last worldwide pandemic and what was it?
Swine Flu (H1N1) in 2009 emerged in Mexico
What occurs in the nucleus of the cell in Influenza that is unique among human RNA viruses (except retro viruses)
It replicates in the nucleus of the cell.
For antigenic shift to occur, what is required?
Normally requires that the viruses have a segmented genome and more than one host species
Hemagglutinin (H protein) has what specific function?
Facilitates viral attachment and fusion with the cell membrane
Nuraminidase (N protein) has what specific function?
helps viral release by cleaving neuraminic acid on the cell surface
Drift mutations can lead to what? Shift mutations can lead to what?
Drift mutations: Epidemics
Shift mutations: Pandemics
What can be done to determine and diagnose if an influenza virus is the cause of infection?
Influenza viruses agglutinate RBCs. A key technique is based on the fact that influenza viruses can grow in eggs and that they bind sialic acids, which are found on some RBC
How do we determine if a patient has developed neutralizing antibodies to a certain influenza strain?
Hemagglutination Inhibition Assay. Antibodies to spikes of each viral strain can block the RBC agglutination by neutralizing just like they do in vivo. If the antibody is present, RBCs will not agglutinate
What is the innate immunity that hosts use against viral infections?
Interferons (IFN-alpha and IFN-beta) that are pro-inflammatory and inhibit viral replication “hold the fort” until influenza specific lymphocytes can clone
Describe the process when Specific immune system kicks in responding to the influenza virus that replicates too fast or host immunity is inadequate
- Ab neutralizes the free viruses and Tc cells destroy infected cells (viral factories)
- Unfortunately, Tc cell killing can leave lung epithelial cells significantly denuded and susceptible to inhaled normal bacterial flora
*What is secondary opportunist disease?
After Tc cells have killed many lung epithelial cells that were infected with virus, the lungs are left susceptible to inhaled normal bacterial flora. Many deaths from influenza are often from secondary opportunist disease (example: strep or staph bacterial pneumonia)
What are the 3 types of influenza and what identifies them?
A, B, C
Unique capsid antigens identify them
What two types of influenza cause significant human disease?
Type A and Type B
Pandemics generally caused by what type of influenza?
Type A
What types of influenza typically cause Epidemics?
Type A and Type B
What does it mean that Flu vaccines are usually ‘tri-valent’?
They have pools of antigens from three different strains, Two A strains plus one B strain all PREDICTED to be the major strains circulating in a given flu season.
What is a ‘split vaccine’?
The antigens are viral proteins usually with lipids removed in a flu vaccine
What are the advantages of ‘mist’ flu vaccines? (short answer question on exam??? seems like something he’d do)
- Intranasally administered
- Potential to induce a broad mucosal, as well as systemic, immune response.
- Acceptability of an intranasal rather than intramuscular route of administration
Where were ‘mist’ flu vaccines first used and when did the U.S. first market these types of vaccines?
In Russia
In 2003 they were first marketed in the U.S.
Are antiviral drugs a possible substitute for vaccination?
No
What are the four major, licensed influenza antiviral agents available in the US?
Amantadine
Rimantadine
Oseltamivir (Tamiflu)
Zanamivir (Relenza)
Which drugs have activity against influenza A viruses but not B viruses?
Amantadine and Rimantadine
How do Amantadine and Rimantadine act?
By mainly blocking uncoating of viruses. Thus, the viral infection is stopped and can be used to stop infection before vaccines have had enough time to work.
Which antiviral drugs are known as Neuraminidase inhibitors?
Oseltamivir (Tamiflu)
Zanamivir (Relenza)
How do Oseltamivir and Zanamivir work?
Inhibit neuraminidase and thus block the viral release.
Oseltamivir and Zanamivir have activity against what influenza virus strains?
A and B
Which antiviral drugs are known as adamantanes?
Amantadine and Rimantadine
How infectious is Influenza virus?
Highly infectious viral illness
How many deaths occurred worldwide in the ‘great’ pandemic of 1918-1919?
50-100 million deaths
What type of influenza affects primarily very young children and elderly?
Type B, milder epidemics
What influenza has no epidemics and is rarely reported in humans?
Type C
Which influenza strain affects just humans?
Type B
Which influenza strain affects humans and animals?
Type A
Is Viremia usually demonstrable in influenza virus?
No not usually demonstrable
Incubation period of Influenza virus?
Incubation period of 1-4 days
What is the mode of transmission for Influenza virus?
Respiratory
Probably Airborne and Hands
State a few reasons that pneumonia and influenza mortality varies depending on time of year
In winter or colder months, kids have school and are around infection often.
Enveloped influenza doesn’t dry out in the winter.
In warm months, Vitamin D from UV light allows immune system to act stronger
Duration of immunity of influenza vaccine?
<1 year
