Lecture 4 Flashcards
True or false: most infections have no consequence and many infections are inapparent
true
why was the west nile virus infection so bad
-it spread in the USA in less than 4 years
-1 000 000 infections by oct 2004
-febrile illness developed in 20% neuro invasive 1%
-most people infected had no obvious disease=inability to stop the epidemic because it cannot be recognized early
What is pathogenesis?
The process of producing a disease
How does the virus enter the host? Host response? Where does replication occur? How does the infection spread? What tissues are infected? Acute or chronic? Transmission? etc.
What are the 2 effects of viral disease?
-effects of viral replication on the host
-effects of host response on the virus and host
True or false: effects of host response on the virus and host are not the ones that create symptoms
false usually they are the ones that will create symptoms like our body response to a bad virus will be to have fever and that is what we usually feel
What are the requirements of a successful infection?
-sufficient quantity of virus
-accessible, susceptible and permissive cells
-local antiviral response absent or overcome
what are good barries of our body against viruses?
skin
eyes thanks to tears
mucus
What is a susceptible cell?
A susceptible cell has a functional receptor for a given virus - the cell may or may not be able to support viral replication
if it is not able to support viral replication it might need smth else that is tissue specific
What is a resistant cell?
A resistant cell has no receptor - it may or may not be competent to support viral replication
even if the virus can’t enter the cell, if you introduce the virus in other ways like through an infectious cDNA or transfect the rna into the cell, it might support replication
What is a permissive cell?
A permissive cell has the capacity to replicate virus - it may or may not be susceptible
True or false: a susceptible and permissive cell is the only cell that can take up a virus particle and replicate it
true
What are the places where a virus can gain access
-skin
-mucosal surfaces
respiratory tract
alimentary tract
urogenital tract
-eye
-fetus (transplacental perinatal)
what is required to maintain the chain of infection?
spread from one susceptible host to another
what are the 2 general patterns for transmission of infection?
-Direct transmission (i.e. human-to-human)
-Vector-borne (i.e. mosquito-to-human)
What does isolation mean?
Isolation - separates sick people with a contagious disease from people who are not sick
What does quarantine mean?
Quarantine - separates and restricts the movement of people who were exposed to a contagious disease in case they become sick
These people may have been exposed to a disease, or they may have the disease but do not have symptoms
what does nosocomial mean and why us it so common
Nosocomial - when an individual is infected while in a hospital or health care facility
so common cuz we stick lots of sick people in there
what does iatrogenic mean?
Iatrogenic - activity of healthcare worker leads to infection
ex: reused needles
What does horizontal transmission mean?
Horizontal transmission - between members of the same species (zoonotic = different species to another species)
like animal to human
What does vertical transmission mean?
Vertical transmission - transfer of an infection between parent and offspring
what does germ line transmission mean?
Germ line transmission - transmitted as part of the genome (e.g. proviral DNA)
True or false: after replication at the site of entry, viruses all remain localized
falseeee
-After replication at the site of entry, viruses may remain localized but some might spread beyond the primary site aka disseminated like the dengue virus
-if many organs are infected = systemic
-physical and immune barriers must be breached
what is viremia?
presence of virus in blood
usually, you have the passive viremia wich is the inoculum, then the primary viremia which is the 1st replication at the source of origin, then the secondary viremia which is the secondary replication at the distal sites
what was the cause of lots of contaminated blood supplies in the 80s
Hep C because at that time we did not do some blood screenings before taking blood from donors
what is the viral spread of mousepox?
virus goes through lesion in skin then replicates in lymph nodes
-goes to the blood
-replicated in liver and spleen
-goes in the blood and shed on skin
=rash on skin
What is tissue tropism
-The spectrum of tissues infected by a virus
Enterotropic, neurotropic, hepatotropic, etc
-ranges from limited (like hep C which pretty much only infects the cells in liver) to pantropic (like polio which pretty much infects every cells)
What are the determinants of tissue tropism
Determinants: susceptibility (does the cell have the receptors), permissivity (can the cell support the replication), accessibility (which barriers have to be breached? like the BBB is stronggggg), host defenses, etc.
What does virus shedding mean?
-Virus Shedding - respiratory secretions (aerosols aka skinny particles), nasal secretions, mucosal shedding, skin lesions, blood/blood supply, urine, semen, feces, insect vectors, germline/vertical
-The number and viral load of aerosols produced through speaking and other expiratory activities can be higher than those of droplets
Airborne transmission
-If you can inhale particles - regardless of their size or name - you are breathing in aerosols (1 min speaking ~1000 aerosols)
- Long range (aka smaller particles) vs short range (aka bigger particles) (e.g. being close to someone who is smoking)
- Wearing masks, keeping your distance, and reducing occupancy indoors can impede transmission
- But, the tiniest suspended particles can remain airborne for hours - good ventilation is important!
True or false: infections at close range=droplet transmission
falseeee
aerosol can also occur at short distances
Infection control strategies for respiratory viruses have focused on limiting….
-Infection control strategies for respiratory viruses have focused on limiting droplet and fomite transmission
-Some of these strategies are also partially effective at limiting aerosol transmission
- Erroneous conclusion: efficacy proved droplet transmission?!
-covid aerolized stays 1-3hs in the air
Why was Measles virus so cray cray?
-measles created infectious centers on mucosal cells
-instead of killing the cells these centers peel off the surface of the airway and gets to mucus rich spots like the nose
-it gets expelled off and lands on surfaces
=virions and cells go off when someone sneezes
What is an example of a virus that was from one place and that then got to another place?
Chikungunya virus that was og in europe and afrika
-it used the Aedes aegypti fly that is only found in europe and afrika
-got a simple aa change and now the Aedes albopictus was able to also carry it and now it is in the US
true or false: seasonality affects viral transmission
true
what are 2 things that influence seasonality
humidity and behavior ex: during winter we stay more inside
True or false: virus particles are too big to diffuse across the plasma membrane
true this is why they need to be taken up by specific pathways
true or false: the entry process is a passive process
false
it is an active process
How do virus particles find the ‘right’ cell?
- Adhere to a cell surface (electrostatics) = NO specificity
- Attach to specific receptor(s) on cell surface
- Penetration
- Transport and uncoating (transfer genome inside the cell)
Cellular receptors are essensial for….
Essential for all viruses except those of fungi (no extracellular phase) and plants (enter cells by mechanical damage)
when was the first cellular receptor identified?
1985: sialic acid: influenza virus
Development of technologies facilitated identification of viral receptors (i.e. monoclonal antibodies, recombinant DNA technology, etc)
What is monoclonal antibodies
an antibody against a cellular receptor that you think is the receptor for your virus and then you treat the cell with that antibody and it binds and blocks viral entry= might be the receptor for the virus
what use is recombinant DNA technology
you can have a cell type that is permissible but not susceptible and then you add a receptor
-if it is now susceptible=that is the receptor for your virus
True or false: different entry receptors have different cellular functions
which one is the false statement?
Different viruses can have the same receptor
Viruses in the same family may bind different receptors
One virus may bind multiple receptors
A virus may use different receptors on different cell types
they are all true lol
How does Zika get into the cell
-it binds to Gas6 which can then use axl to get into cells
True or false: non-enveloped viruses can fuse to the plasma membrane
false
they can’t fuse with the plasma membrane
Non-enveloped viruses get access through receptors by binding to the capsid surface(ex: polio) or via a protrusion (adenovirus)
sometimes they can either directly inject their genomes or trigger endocytosis and uncoating
-has to occur after they escape from the endosome
how does the adeno virus bind a cells membrane?
it uses protrusions that interacts with CAR receptors
How do enveloped viruses bind cell membranes?
via glycoproteins like influenza
What is the role of co-receptors in viral infection?
Sometimes viral receptors are not accessible at the surface of the cell
- e.g. Coxsackie group B viruses require two receptors: Decay-accelerating factor (DAF) and CAR (coxsackie- adenovirus receptor)
-it binds to DAF first then DAF drags the virion to the tight junction where it can interact with CAR= triggers caveolae and entry of Coxsackie
Penetration and Uncoating at the Plasma Membrane: Paramyxoviruses (fusion induced at the plasma membrane)
on the viral membrane, you have HN and F1-F2
-the fusion peptide breaks (I’m unsure) and then HN will attach itself to the cell membrane on one of its receptors
-conformational change forces F protein to stick to the host cell surface
-hair pining motion brings the 2 membranes close together so that they are close enough to exclude water
=membrane fuse
Fusion at the Plasma Membrane: Human immunodeficiency virus (HIV)
there are SU and TM which is the fusion peptide
-receptor binding: Su binds to CD4 then there is a CCR interaction
-conformational change
-TM sticks to the cells membrane
-conformational change: hairpin motion=viral fusion
What are the 2 ways for a virus to get inside a cell
-phagocytosis and endocytosis
What are the 2 different endocytosis?
-macropinocytosis which is like this ruffling of the membrane that takes in the viral particles
-Receptor mediated endocytosis which is when the ligand binds to a ceceptor (clathrin) and can then get inside the cell
True or false: high pH in the endosome can trigger fusion of many enveloped virus
falseee it is low pH that can do that
viral fusion at the endosomal membrane
low pH= conformational change and the viral receptors will bind with the endosome’s receptors
-hairpin motion
-and then the 2 membranes will fuse and the virion can then escape the endosomal bubble
Class I fusion proteins
-kinda like spikes, they stick out of the viral particle
-Perpendicular to membrane (spikes)
-Mostly alpha- helical
-Form trimers
Class II fusion proteins
-lie flat on the surface
-parallel to the membrane
-mostly beta-sheets
-form trimers of dimers
true or false: ebola has a weird way of getting inside the cell
true
-it interacts with an unknown receptor then it’ll get inside the cell
-it’ll then interact with NPC1 another receptor and it’ll fuse
Fusion is a regulated process
-Must not occur in the wrong location!
-Neutral pH (plasma membrane)
Second protein receptor interaction to trigger the interaction for fusion
-Low pH fusion (in the Endosome)
Proteolytic cleavage activates the fusion protein for fusion (Class I)
Cleavage of a second protein (Class II) activates the fusion protein
Endosome fusion receptor
Non-enveloped viral entry
-Non-enveloped viruses (no membrane) = cannot mediate membrane fusion!
-Typically rely on rupture of cell membranes
(ruptures endosome)
- -e.g. Adenovirus pokes holes in the endosome
-e.g. Poliovirus (creates a membrane channel to get material in)
What are other mechanisms of fusion
-virological synapse
-cellular conduits
-extracellular viral assemblies
True or false: movement of large particles (>500 kDa) does not occur by passive diffusion
true
Viral particles are transported in the cytoplasm on…
actin and microtubule cytoskeletons
Virions and capsids are transported within the cell in…
vesicles or on microtubules
Trur or false: the movement within cell nis active
true: virions, endosome or the lysosome are actively transported
Getting into the nucleus
-Wait for cell division (breakdown of nuclear membrane) to hop in cell before it gets build up again
-Could contact with nuclear pore complex
Nuclear localization signals (NLS), docking at the nuclear pore, nuclear membrane disruption
Adenovirus docking at the nuclear pore
It uses kinesins and dyneins to move on the microtubule, when it gets to the pore it binds tightly
-when the kinesin move back, it rips open the capsid and the viral genome can zip in
Attachment factors and entry receptors help mediate viral entry
-Enveloped viruses interact with receptors through envelope glycoproteins
-Non-enveloped viruses interact with receptors at the capsid surface
True or false: non-enveloped viruses typically rupture cellular membranes
true
