Lecture 2 TYJ Flashcards
What are the 5 important steps of the viral life cycle?
1) attachment
2) penetration and uncoating
3) synthesis (of viral genome and protein using hot machinery)
4) assembly
5) release (budding)
What are the 2 proteins important for attachement?
viral surface protein and cellular receptors
cell receptor and tissue tropism
- some viruses attach to many types of tissue
- some viruses attach to only one single tissue
- dependent on the presence of specific cellular receptors that can interact with the viral particle
(contributor to tissue tropism)
Cell receptors are what type of protein? what about salic acid receptors?
cell receptors are transmembrane proteins
salic acids are non protein receptors
Cell receptors found on multiple tissues in the body can result in?
Zoonotic transmission
Cell receptors found only on one type of tissue in the body
eg: respiratory viruses
describe characteristics of Influenza A viruses
- has 4 types (type A, B, C and D)
- A and B IAV resulted in seasonal flu and resulted in H1N1 and H3N2
- type C can cause mild diseases in children
type D does not infect humans, circulates in animals
what are the 2 important spike proteins present on IAV?
hemagglutinin (HA) and neuraminidase (NA)
How are IAV classified?
they can be further classified within their types eg: influenza A are classified based on the sequence of their spike proteins (HA and NA)
H1N1 and H3N2 are commonly circulating in the human population
H5N1 occasionally can infect humans, especially when they are in constant close proximity with infected animals
What cellular receptors does IAV in humans bind to?
upper respiratory track - alpha 2-6 sialic acid receptors (spreads fast rarely fatal)
lower respiratory track - alpha 2-3 sialic acid receptors (spreads slow often fatal)
H5N1 can occasionally spread to humans why is that so?
animals have the alpha 2-3 sialic acid receptors that binds specifically with H1N1 spike proteins of the IAV if it infect humans the virus would cause serve infection as it affects the lower respiratory track consisting of the lungs, bronchioles and alveoli
SARS-Cov-2
(+) sense, single stranded RNA virus, enveloped
Influenza virus
(-) sense, single stranded RNA virus, enveloped
after attachment comes penetration, what are the 2 key procedures that happens
1) fusion
2) receptor mediator endocytosis, encapsulated the virus into a specialized vesicle known as endosomes
what are the 3 uncoating methods
1) uncoating at the plasma membrane (direct penetration, no endosome)
2) uncoating within the endosome (the acidic environment encourages fusion as it causes conformational changes of the envelop membrane and results in the uncoating to release the viral genome)
3) uncoating at the nuclear membrane (nucleocapsid arrive at the nuclear membrane and docks at the nuclear pore to release the viral genome)
what are the 3 transportation pathways
1) membrane mediated endocytosis
- helps viral particles to pass through the plasma membrane
2) microtubules dependent trafficking
- helps viral components move within the cytoplasm
3) nuclear transport
- import and export viral proteins through the nuclear membrane
during uncoating, what type of virus uncoats their nucleocapsid in the cytoplasm and what type uncoats their nucleocapsid in the nucleus?
RNA viruses uncoats in the cytoplasm
DNA viruses uncoats in the nucleus
Adenovirus (naked virus, DNA genome), describe how the DNA genome gets transported to the nucleus
for DNA viruses the nucleocapsid do not uncoat in the cytoplasm but instead they make use of the motor proteins (dynein and kinesin-1) that transports the nucleocapsid via the cytoskeleton (made from microtubules, actin and intermediate filament) of the host cells, once it reaches the nuclear membrane it docks its capsid and release the viral genome into the nucleus
Dynein and kinesin-1
motor proteins that moves in an opposite direction
dynein move towards the negative ends while kinesin-1 move towards the positive ends
implications for antiviral therapy (vaccination)
person can acquire adaptive immunity from receiving vaccination, as it stimulated the immune cells to produce antibodies that specifically targets the components of the virus particles
what are the 4 types of vaccines available?
1) subunit vaccines (gene based vaccines)
2) virus like particles (VLP) for HPV and HBV
3) inactivated virus vaccine
4) live attenuated vaccine
Subunit vaccines
vaccine has some of the viral components, could be the viral capsid protein or the surface spike protein
eg: mRNA based COVID-19 vaccine
- isolate the RNA gene from infected individual, specifically and only sequence the gene that codes for the spike protein of the virus
- lab made nucleotide sequence of the gene that codes for the spike protein (mRNA synthesis)
- vaccine has the mRNA sequence, injected into individual
- body of individual produce the spike protein
- have to have prior knowledge of the target gene sequence and know the point of attachment of the virus
virus like particles (VLP)
for HPV and HBV
- both viruses are dsDNA and circular, HPV is naked virus and HBV is enveloped
- vaccine contains structural proteins that are non infectious because there is no viral genome present
- for HPV, they input the L capsid protein from 2 or more HPV types
- for HBV, they input the viral surface antigen (hepatitis B surface antigen)
- HBV and HPV viruses are hard to culture and they do not grow well in culture hence cannot design inactivated vaccines)
inactivated vaccines
inactivated influenza vaccine (IIV)
1) culture the virus and virus propagation in the embryonic eggs
2) chemically inactivate the virus using formalin
3) isolate the viral surface protein responsible for attaching onto cellular proteins (eg: HA and NA)
Live attenuated vaccine
live attenuated influenza vaccine (whole virus vaccine)
- vaccine contains the entire virus particle but they are in the weaken and attenuated form
- advantage is that it stimulates the immune cells B and T cells to produce antibodies that targets all of the viral proteins available (broad immunity)
- administered as a nasal spray and targets the upper respiratory track
SARS-Cov-2 viruses and vaccines
the mRNA based COVID 19 vaccine stimulates body T and B cells to produce antibodies that targets the S1 and S2 epitopes of the spike proteins
S1 is responsible for the binding of the virus to the ACE2 receptors found on the upper respiratory track, antibodies binding to S1 epitope prevents attachment of the virus to the receptor
S2 is responsible for fusion and merging of the viral envelope to the cell membrane, antibodies binding to S2 epitopes would prevent penetration and uncoating
multi latent vaccines
vaccines that targets multiple strain of viruses and not just 1 strain
eg: dengue has 4 serotypes and the vaccine should stimulate the body to produce antibodies that targets all 4 serotypes
IAV vaccines should target both type A (H1N1 and H3N2) and type B
