7.1 Viral Adaptations Flashcards
Explain the difference between (+) and (-) RNA viruses
Positive RNA can enter the host ribosome and form proteins.
Negative strands cannot enter the ribosome, hence cannot form their own protein
4 main things a virus must do to successfully invade a host
1) Attach
2) Enter
3) Replicate
4) Exit
Once viral nucleic acids are recognised and bind what is activated?
What 3 things does this do?
Binding -> activates transcription factors ->production of interferon alpha or beta
IFNa and INFb do the following:
1) Induce Resistance to viral replication in all cells.
2) Increase expression of ligands for receptors on NK Cells
3) Activate NK Cells to kills virus infected cell
What are the 2 outcomes the body tries to achieve with the immune response to viruses?
Incl Adaptive and Innate immune stimulation
Two main outcomes the body wishes to achieve with the immune response
1) Protection against infection
Innate: Type I Interferon is released
Adaptive: B-lymphocytes are activated ➞ produce Antibodies which neutralise the virus
2) Eradication of established infection
Innate: NK cells are stimulated to kill the infected cell
Adaptive: CD8+ cells are stimulated to kill the infected cell
What system does Influenza target?
Respiratory system: Influenza virus prefers the respiratory epithelium
What is the most common mode of transmission of Influenza?
Direct droplet transmission
What are the 2 most common groups affected by Influenza and why?
1) Very young children: lack antibodies to virus because no prior exposure. Also have a small diameter of respiratory tract components so inflammation and swelling can lead to blockage of resp tract, sinuses or eustachian tubes.
2) In the elderly: often severe because of an underlying decreased effectiveness of the immune system and/or chronic obstructive pulmonary disease or chronic cardiac disease
Influenza virus is an orthomyxovirus, what does this mean?
A family of single-stranded RNA viruses that have a spherical or filamentous virion with numerous surface projections of glycoprotein
What are the 3 major serotypes of the Influenza virus? What differentiates them?
3 major serotypes of virus: A, B, and C.
Differences are based on antigens associated with the nucleoprotein.
What are the 2 key proteins involved in the entry and exit systems of influenza?
What do each of these do?
1) Neuraminidase (NA): glycoprotein thathydrolyses mucus on respiratory epithelia, then digests sialic acid on cell surface allowing virus to be internalized upon binding. Removal of sialic acid also makes it easier for progeny virions to exit the cell.
2) Hemagglutinin (HA): allows attachment + membrane fusion with endosome. (Receptor binds to a site on the virus that is not exposed to the immune system)
What is the pathogenesis of Influenza?
1) virus taken up by epithelia cells via endocytosis
2) engulfed by an endosome (high pH) which causes a change in configuration of outer antigens
3) viral envelop proteins then fuse with membranes of phagocytosis vesicles ➞ allows genetic info to enter cytosol
5) once released it shuts down normal production of nucleic acids and starts producing viral proteins on surface of the host cell.
6) via a budding process the new virion particles leave the host cell and infect other cells
Why are secondary Infections common with Influenza?
List 3 possible bacteria that cause this
As influenza kills the epithelia cells and removes the epithelia lining and reduces ciliary clearance, the gaps formed provide other pathogens with access hence the host is more susceptible to developing secondary infection.
1) Haemophilus influenza
2) Streptococcus pneumoniae
3) Staphylococcus aureus
Where does influenza multiply?
What are the 4 functional and structural abnormalities influenza causes in the cell
Virus multiplies in the ciliated cells of lower respiratory tract.
Functional and structural abnormalities:
- Cellular synthesis of nucleic acids and proteins is shut down.
- Ciliated and mucus-producing epithelial cells are shed.
- Substantial interference with clearance mechanisms
- Localized inflammation
When new influenza virons exit a host cell how do they avoid detection by host immune cells?
Upon budding it takes a portion of the original cell membrane which acts as a protective system so it is not recognised by the immune system as being foreign
List 4 signs/symptoms of influenza
Sudden fever pharyngitis congestion cough myalgia
Which influenza serotypes are causative agents?
Influenza virus types A and B
Why produces the symptoms of influenza?
Immune response to the virus
What are the two main processes that produce mutations of viruses + explain each
Which of these processes is specific to a influenza serotype?
1) Antigenic drift - Accumulation of hemagglutinin and neuraminidase gene mutations with a single strain of virus in a single place. This is a slow process.
2) Antigenic shift – Assortment of the genes among different influenza A viruses infecting the same host cell.
Eg. host cell may be infected with 2 viruses. Within host a chymeric change occurs causing gene transfer resulting in the production of new antigens and a novel virus
Influenza A does shift (B cannot)
What are the 2 basic approaches to treatment of Influenza?
1) Symptomatic care
2) Anticipation of potential complications
What are the basic treatments of influenza?
- Rest and fluid intake
- Analgesics for myalgia and headache
- Cough suppressants
What 2 antiviral drugs can be used to treat Influenza?
What is the problem with these?
Amantidine and rimantadin
Only useful if the infection is diagnosed within 12-24 hours.
What 2 vaccines are available for Influenza?
1) Trivalent inactivated vaccine (TIV) - via IgG antibodies.
2) Live, attenuated influenza virus vaccine (LAIV) - given nasally and provides mucosal, humoral and cell-mediated immunity.
What are the 3 components of Epidemiologic Homeostasis
Host
Agent
Environment
When does an epidemic occur?
When there are significantly more cases of the same disease than past experience would have predicted
What family of viruses does COVID19 belong to?
Subfamily Coronavirinae in the family Coronaviridae
Describe the structure of COVID19
- enveloped viruses
- positive- sense RNA genome
- nucleo-capsid of helical symmetry
What does Corona virus primarily infect?
the upper respiratory and GI tract of mammals and birds ➞ can also cause infection in lower resp tract too causing pneumonia
What is a possible therapeutic target against COVID19?
make antibodie generated against the spike proteins to stop them binding to receptor
What were the previous 2 strains of corona virus known as before COVID19
SARS-CoV-2 (Sever acute respiratory syndrome)
MERS (Middle East respiratory syndrome)
Describe the viral adaptations of Corona virus?
Within the spike region of COVID19 is a cleavage site that is optimised to bind to the human ACE II receptor.
These spikes also increases the stability of binding and entry into human cells
Describe the pathophysiology of corona virus (incl its entry mechanism)
1) COVID19 virus binds ACE II receptor on epithelial cells of resp tract through spike proteins
2) binding mediates proteolytic cleavage followed by fusion with host membrane
3) Viral RNA is released into the host cell cytoplasm, where viral nucleoproteins are uncut
4) viral proteins are translated to make new viral proteins
5) vessicles fuse with the cell membrane and release COV virions into the lumen
COVID gets in and gets out the same way, what is this known as?
Why does this result in significant damage
Apical infection and Apical release
More virulence factors attacking the site and more viron particles leaving leads to a large degree of epithelial damage
