WEEK 1: INFLUENZA VIRUSES Flashcards
Acute respiratory tract infection caused by influenza viruses can be:
Sporadic
Seasonal
Epidemic
Pandemic
Define the terms.
Sporadic: No regular or predictable pattern
Seasonal: Regularly at a certain time of the year
Epidemic: Epidemic diseases are diseases that affect a large number of people in a specific population or area in a short time, more than what is normally expected
Pandemic: A pandemic is an epidemic of an infectious disease that has spread across a large region, for instance multiple continents or worldwide, affecting a substantial number of individuals.
What is an endemic?
Give examples of endemic diseases in Botswana.
An endemic disease is a disease that is always present in a particular population or region.
It often occurs in cycles and has a predictable rate of infection.
Some examples of endemic diseases are the flu, malaria, HIV, and syphilis.
Illnesses range from mild to severe disease
According to WHO (Jan 2023) epidemics of seasonal influenza result in 3-5 million cases of severe disease and about 290 000 to 650 000 respiratory deaths.
In industrialized world’s most deaths occur in ____________VS in developing countries which accounts for an estimated 99% of influenza related deaths in __________.
In industrialized world’s most deaths occur in 65 years or older VS in developing countries which accounts for an estimated 99% of influenza related deaths in under 5.
State and describe the 4 types of influenza viruses.
Type A – cause potentially most severe disease, epidemics and pandemics, cause infection in humans, birds and other mammals
Type B – less severe disease, can cause epidemics, almost exclusively human infection although more recently infection in seals and pigs (mostly experimentally) reported.
Type C – antigenically stable, mild to asymptomatic illness, minimal public health impact, also almost exclusively human infection but infection in pigs reported.
Type D – no epidemiological relevance to humans, found in cattle.
No epidemiological relevance to humans, found in cattle.
Name the virus.
Type D
cause potentially most severe disease, epidemics and pandemics.
Type A
Which influenza affects humans only?
Type B
How many gene segments and viral proteins are found in the following types of influenza viruses?
A
B
C
A: 8 gene segments, 10 viral proteins
B: 8 gene segments, 11 viral proteins
C: 7 gene segments, 9 viral proteins
Influenza can be traced as far back as______.
Hippocrates described a cough outbreak in ______in present day ________at the turn of autumn.
Influenza can be traced as far back as 400 BC
Hippocrates described a cough outbreak in 412BC in present day Turkey at the turn of autumn.
State the years for the occurrence of the following pandemics.
*Spanish FLU
*Asian FLU
*Hong Kong FLU
*H1N1
1918 – Spanish FLU
1957 – Asian FLU
1968 – Hong Kong FLU
2009 – H1N1
What is the family of influenza viruses?
Describe their general structure and genome.
Family: Orthomyxoviridae – spherical/tubular
Enveloped (host derived lipid bilayer)
SEGMENTED negative-sense single-strand RNA segments with EIGHT SEGMENTS.
State the functions of the following structural proteins and where they are found.
Hemagglutinin (HA)
Neuraminidase (NA)
M1 (matrix protein)
M2 (ion channel)
THREE polymerase proteins PB1, PB2, and PA
NEP (nonstructural protein 2)
Nucleoprotein (NP)
- Hemagglutinin (HA): A glycoprotein on the surface of the virus that binds to sialic acid receptors on host cells and mediates viral entry. It also determines the subtype of influenza A virus12.
- Neuraminidase (NA): A glycoprotein on the surface of the virus that cleaves sialic acid residues from host cell membranes and viral particles, facilitating viral release and spread. It also determines the subtype of influenza A virus12.
Neuraminidase is also known as sialidase because it breaks the linkages between sialic acid and cellular glycoproteins and glycolipids found in cell walls.
- M1 (matrix protein): A protein that forms a layer under the viral envelope and maintains the shape and stability of the virus. It also interacts with viral RNAs and other proteins3.
- M2 (ion channel): A protein that forms a proton channel on the viral envelope and allows protons to enter the virus, lowering the pH and triggering the fusion of HA with host cell membrane3.
- PB1, PB2, and PA (polymerase proteins): Three proteins that form a complex with viral RNA and nucleoprotein (NP) and act as RNA-dependent RNA polymerase, synthesizing viral RNA from viral RNA template.
- NEP (nonstructural protein 2): A protein that binds to viral RNPs and mediates their export from the nucleus to the cytoplasm.
- NP (nucleoprotein): A protein that coats the viral RNA segments and forms the viral RNPs. It also interacts with polymerase proteins and M1 protein.
Describe the viral replication of influenza virus.
- the HA receptor-binding site attaches the virus to surface glycoconjugates that contain terminal SA residues.
- Virus endocytosis, taken into the cell in an endosome.
- Acidification of the endosome by proton entry via M2 ion channels allows for uncoating of the virus.
- Nucleocapsid sent to the nucleus.
- There is transcription and translation forming mRNA and -ssRNA
- mRNA taken to the ER where it is used to form Hemagglutinin and neuraminidase.
- The viral genome and HA, NA migrate to the surface where they bud off as a new virion.
Their release is highly dependent on the sialidase activity of NA.
Where do Influenza viruses replicate within?
How is that an advantage and a disadvantage?
Influenza viruses replicate within the nucleus of the host cell.
This uncommon RNA virus trait provides influenza with the advantage of access to the nuclear machinery during replication.
However, it also increases the complexity of the intracellular trafficking that is required for the viral components to establish a productive infection.
State the Influenza virus structural differences.
- Unlike Type A, Type B have NB and BM2 structural proteins instead of the M2 ion channel, the latter which is said to have same functional activity as M2 protein.
*Increasing pH in endosome to facilitate uncoating
*Maintaining viral membrane PH during entry and trans Golgi apparatus transport
- Type C has hemagglutinin-esterase-fusion (HEF) which corresponds to HA and NA, as well CM2 structural protein.
Describe the simplified Influenza virus simplified pathway.
- Virus
- Superficial epithelium of respiratory tract
- Inflammation
- Necrosis
Outline the differences between antigenic shift and drift.
DRIFT
*Minor changes
*Happens in Type A and B
*May result in epidemics
*Results from point mutations
*Lead to changes in the surface proteins called HA and NA
*Changes happen gradually
SHIFT
*Major changes
*Happens in Type A only
*May result in pandemics
*Result from exchanging of gene segments.
*Combine to form a new subtype with a mixture of surface antigens from the original viruses
*Changes occur abruptly.
Describe the mode of transmission for Influenza viruses.
predominantly by aerosol infection, i.e. relatively large droplets (>5 μm) created particularly while talking, coughing, or sneezing.
transmission might occur by (droplet cores) which are smaller (<5 μm) and able to remain in the air for longer periods (aerogenic transmission).
transmission can occur by direct contact with virus-contaminated surfaces (fomites) (e.g. shaking hands) and subsequent mouth-nose contact.
After infection the viruses replicate in the nasal and laryngeal mucosae. This replication also affects the lower airways as the infection progresses.
Avian influenza was transmitted form birds to humans.
State the modes of transmission.
Bird to human
Fecal-oral (poultry excreta)
Direct contact
Ingestion of undercooked food
What is the difference between flu and cold?
Flu presents with the following which are rare in cold.
Fever, headache, body ache
Flu has gradual onset and can have severe symptoms and there is no sneezing.
Cold has gradual onset and presents with mild symptoms.