Flu Flashcards
Transmission of Flu
Through air; not necessarily an aerosolizing illness but is airborne; 10^5 – 10^6 virions per droplet of aerosol
18-72 hour incubation time – relatively fast
Death from the Flu
36,000 per year
Hospitalized from flu
114,000 in the US
Who is most susceptible
Very young and very old
Structural Definition of Flu Virus
Orthomyxovirus
Enveloped
Helical nucleocapsids
Segmented -ssRNA genome (8 segments)
Genome segments coiled like a telephone cord
Virions are pleomorphic
Tend to be rods when pulled right off of people
Two Kind of Spikes
Neuraminidase and Hemagglutinin
there are eight pieces of RNA, and each of them is surrounded by their own proteins. All right, these are the segments, each of them encodes either one or two proteins. Alright, so the NA, the neuraminidase is encoded by its own segment, the hemagglutinin encoded it by its own segment .
There are 17 HA and 10 NA classes
Fear with Flu transmission from animal to human
Every animal pretty much gets the flu, however, even though it transmitted from an animal to a human was 100% fatal or 80% fatal, it hasn’t acquired the characteristic to transmit from human to human
So that’s what people are really afraid of, is one of these arising that’s even 50% fatal even 20% can acquire that plus the ability to the spread from human to human
Where does it replicate?
Influenza virus replicates in the epithelial cells throughout the respiratory tree, with virus being recoverable from both the upper and lower respiratory tract.
**no viremia in seasonal flu ; only severe pandemic flu can cause viremia
Antigenic Drift
A cell infected with 1 virus can only produce viruses identical to the infecting virus, or viruses with point mutations generated during replication
It’s like a regular mutation where single base pairs are incorporated and you get a change, so you got to change the protein being encoded
SLOW over time
Antigenic Shift
Reassortment occurs when a cell is infected with >1 different viruses
Example: Virus 1: a human flu and Virus 2 is a bird flu and a pig gets infected; within the pig cells, newly produced virions with segments from the bird and human viruses will now be encoded as H and N antigens that humans may have less immunity against.
Influenza Types
Type A causes epidemic/pandemic flu in humans. It mutates (drift), and reassorts (shift) during passage through humans and animals (birds, pigs, horses, marine mammals). Aquatic birds are the main reservoir and mixing of avian and animal flu viruses mainly occurs in animals such as pigs.
Type B causes non-epidemic seasonal flu.
Mutates and reassorts. B/Victoria and B/Yamagata reassort. Infects (almost) only humans. Seals can be infected.
Type C does not cause serious disease in humans. Mutates only (antigenic drift), so there are no subtypes. Infects only humans but we're vaccinated
Virus Nomenclature
Influenza type Species isolated form (unless human) Place of Isolation Strain designation (Strain number) Year isolation H#N# subtypes
Example
A/Hong Kong/1/68(H3N2) A/duck/Seattle/35/1985(H1N1) B/Perth/1/1976
HA - Hemagglutinin
also called “H”
Binds to sialic acid on cells for entry
Mediates binding and entry into cells
Hemagglutinates red blood cells - can be used for diagnosis
Elicits protective antibodies that neutralize the virus
H1, H2, etc. are the different forms of HA that represent antigenic shift
Minor mutation result in antigenic drift that makes new strains each season
NA - Neuraminidase
also called “N”
Cleaves sialic acid, which allows virus to be released from cells
Target of antiviral drugs zanamivir (Relenza) and oseltamivir (Tamiflu)
(reduce the time-to-symptom resolution by 1.5 days if therapy is started within 48 hours of the onset of symptoms)
N1, N2 represent distinct forms with different antigenicities
Antibodies against N do not neutralize virus, but do reduce virus release
Viral Life Cycle of Flu
Hemagglutinin (spike on flu virus) binds to sialic acid on cells. Sialic acid is a modification of surface proteins that is on cells and it’s mainly on the cells lining the upper respiratory tract and the lower respiratory tract.
2) Forms endosome inside cell (target for old flu medication Amantadine which disabled the M2 protein, preventing the uncoating of the virus and making it inert)
3) Uncoats and fuses with nuclear membrane to get into nucleus
4) replication of viral RNA
5) synthesis of viral proteins via ER
6) Budding out of cell with help from NA which cleaves sialic acid in the area to allow virus to be released (target for most flu drugs today)
Tissues infected by Flu
viruses infection of columnar epithelial cells in lower respiratory tract causes the tracheal mucosal epithelium to lose ciliary cells until recovery. This makes you vulnerable to secondary bacterial infections.
Pathogenesis
Virus kills the cells it infects.
Disrupts ciliary action, making patient susceptible to secondary bacterial infections.
Bronchitis and pneumonia can result from influenza directly but usually are the result of secondary infection.
Interferon response induced by dsRNA intermediate.
Virus has mechanisms to counter IFN effects on cells
these are partially effective and much of the symptoms are the result of IFN responses
Laboratory diagnosis of Influenza virus infection
Usually done by noting symptoms, time of year, exposures, etc. rather than a diagnostic test.
Quick lab tests are available and detect viral antigens or nucleic acid but they are error prone, both false (+) and false (-) results.
Viral culture tests can also be performed but take longer
A hemagglutinin reaction, something that I have described before, is also a very very quick thing because the virus in your blood agglutinates red blood cells, it makes them stick to each other, so that when you put them in a well, you get a more diffuse pattern, and not a falling to the bottom of the well pattern
Flu Vaccines
Most effective way to prevent influenza
Flu vaccination time in the U.S. (October and November)
Vaccine is grown in eggs
Inactivated trivalent vaccine that contains purified HA and NA
Live, attenuated vaccine, LAIV Licensed in 2003
LAIV (FluMist®) is approved for use in healthy Given to people who are allergic to eggs. people 2-49 years of age who are not pregnant. Given as a nasal spray.
Trivalent Vaccine Composition
Recommendations made based on antigenic analyses of recently isolated influenza viruses, epidemiologic data and post-vaccination serologic studies in humans
Vaccine is a cocktail of 3 virus strains
2 strains of Influenza A
1 Influenza B strain
WHO meets in Feb. to decide Northern Hemispheres vaccine and September to decide on the Southern Hempisphere
2018-2019 Vaccine Composition
Trivalent vaccine:
A/Michigan/45/2015 (H1N1)pdm09-like virus
A/Singapore/INFIMH-16-0019/2016 A(H3N2)-like virus
B/Colorado/06/2017-like (Victoria lineage) virus
Quadrivalent (four component) vaccines are recommended to include the same three viruses above, plus an additional B virus called B/Phuket/3073/2013-like virus (B/Yamagata lineage)
Importance of Flu shot***
even if it doesn’t completely prevent you from getting the flu, having any preexisting immunity that is effective will lessen the symptoms. It will make the disease milder even if you happen to get the flu
Universal Flu Vaccine
Vaccine uses NP, M1 and M2 and internal nucleoprotein, which binds to the viral RNA.
These are highly conserved proteins
play an important role in the stimulation of T-cell responses during influenza infection.
Target these instead of variable regions and form T cell immunity of antibodies
