9. Rhinovirus and Flu Flashcards
Rhinovirus is the Major ____ Virus
common cold
% of US population experiencing the ‘common’ cold
- There are nearly 62 million cases of the common cold annually in the US
- 52.2 million of these cases affect Americans under age ____
62 million infected/309* million total population
= ____% of population or 1 in 5 individuals will have colds.
17
20
The “Rhino” in Rhinovirus
is derived from the Greek, meaning ____.
nose
Incidence of colds: Rhinovirus \_\_\_\_% Influenza 5-15% Coronavirus \_\_\_\_% Respiratory Syncytial Virus \_\_\_\_% Adenovirus < 5% Parainfluenza \_\_\_\_% Enteroviruses < 5%
30-50
10-15
10
5
Rhinovirus- important features of infection
• There are at least 160 strains.
• There is no ____.
• ____ approaches are constantly being developed.
• Transmitted by ____ or ____contact
• ____ is the cellular receptor.
• Optimal replication is slightly below ____ temperature, explaining why the virus resides in the ____ passages and ____ respiratory airways and not elsewhere in the body.
• Viremia does not occur, i.e., Rhinovirus is not found in ____.
And that it results in difficulty to make a vaccination - polio only had 3 strains, so it was easier to produce a vaccine.
Receptor specificity is the reason we aren’t infected by the majority of the viruses that are around us, only the right match can gain entry. Even an analogue virus to a different species cannot infect us because the receptors vary enough.
IMPORTANT pt: reads bullet 6. This virus cannot cause a systemic infection because of its ____.
vaccine aerosol (sneeze) direct ICAM-1 intercellular adhesion molecule-1 body nasal upper blood
replication limitations
Rhinovirus Shedding
• Viral shedding can occur occur a few days before ____ symptoms.
• Cold symptoms peak on days ____ and may last for 3-4 weeks.
• Virus is shed in large amounts:
a ____ viruses per nasal wash.
cold
2-7
million
• Rhinovirus cold symptoms peak on days 2-7 and may last for 3-4 weeks.
A person is most likely to transmit rhinovirus on the ____ day of infection when the amount of virus in nasal secretions is highest.
2nd-4th
Rhinovirus Infection Time Course and Viral Shedding
4 KEY POINTS
- Rhinovirus is shed in large amounts: a ____ virions per nasal washing.
- Viral shedding can occur occur a few days before ____ symptoms.
- Rhinovirus can survive on a hard surface ____ hours after being touched.
- Cold symptoms peak on days 2-7 and may last for 3-4 weeks.
million
cold
18
It is amongst the ____ viruses in size
Rhinovirus is the size of a ____, 28 nm.
Compare to paramxyo virus (____)
150 nm or greater.
smallest
ribosome
measles
Rhinovirus has protein shell that is ____ Shaped. It contains a ____ strand of mRNA inside.
Have ____ facets
10 facets are facing you
icosahedral
+
20
A variety of factors influence survival times
of different viruses outside the body: They include
- ____ features of virus;
- Temperature
- ____
- Light
- Type of ____
Example, HIV has a half-life of ____ days, ____ hr, and ____ hr
at temperatures of 4oC, 20oC, and 37oC, respectively.
Survival times for different viruses can range from minutes to months.
Points out that temperature is key on the surface the virus resides on.
Every virus’ survival capacity is different outside of a host. Rabies can last for ____ minutes. Some viruses can last weeks. Survival capacity is often due to ____ of the virus. (Which also plays a role for survival inside the body, like in our acidic stomachs)
physical humidity surface 9 30 24
16
protein shell
Adenovirus
Duration of persistance: ____
Rhinovrius
Duration of persistance:
____
7 days to 3 months
1 day
Rhinovirus
How is it transmitted?
Transmission of the rhinovirus occurs in one of two ways:
- Touching your skin or environmental surfaces, such as telephones and stair rails, that have the rhinovirus on them and then touching your ____ or ____
- Inhaling drops of ____ full of rhinovirus from the air when a contagious person coughs or ____
eyes
nose
sneezes
Rhinovirus can survive on hands for about an ____.
hour
Rhinovirus Replication Cycle
____ is the mode of entry. Sheds protein shell. Releases nucleic acid “payload”. Then replicates. Takes place in ____.
Key: However the virus came in, that is what it must look like when it comes out. It comes in as a ____ strand virus, so it must replicate and leave as a ____ strand even though that requires making a intermediary ____ strand.
ICAM-1 cytoplasm \+ \+ -
Infectious agents favor certain anatomical locations
that rhinovirus lives in the ____ cavity, and can get into ____ respiratory
TAKE A LOOK AT ALL OF THESE
nasal
upper
Rhinovirus is confined to the cooler environment of the nasal cavity
____ (91-95) is slightly cooler than the rest of the body (98.6). The small temperature difference is very important for rhinovirus since it cannot replicate systemically at ____ temps.
nasal cavity
higher
Rhinovirus Infection is NOT ____
- Rhinovirus causes ____ respiratory tract infections.
- Since Rhinovirus requires the cooler environment of the nasal cavity (91o-95o F) it does not become ____, i.e., it does not enter the blood stream.
- As a consequence, Rhinovirus infection is not systemic.
systemic
upper
viremic
Treatments for Rhinovirus Infection
• NO vaccine due to larger number of ____ (serotypes).
• New drugs that block viral ____ are being developed.
huge number of strains (160+) that makes a vaccine difficult. Which is why there is no vaccine.
strains
entry
The 160 known strains or serotypes of Rhinovirus prevent development of a vaccine.
- When you are infected with one strain you develop ____ to that strain, which may last for many years.
- But then there are all the other strains that you have not yet encountered.
- The elderly may not retain ____ to strains they were infected in the past.
As you get older, you’ve seen more and more rhinovirus since you’ve already seen the virus and developed immunity.
immunity
immunity
Example of why a Rhinovirus vaccine has not been developed
Here, antibody against virus strain-____ is useless against virus strain-____
ICAM-1 receptor again. Rhinovirus interacts with the ICAM-1 receptor on the cell. Antibody against strain 17 (that “we have already seen”) doesn’t block strain 14 from entering the cell.
17
14
After several days, both the ____ and ____ Immune Responses Clear the Rhinovirus Infection.
Innate immune system is the “raw” immunity that doesn’t need to be educated - NK cell, macrophages etc.
Humoral response requires education and uses antibodies but takes ____ weeks.
Vaccinations don’t work immediately, requires about ____ weeks for the adaptive/humoral response to kick in.
innate
adaptive
2-3
2
Rhinovirus binding to the ICAM receptor on the epithelial cells (EC) of the nasal cavity promotes an innate immune response
ECs secrete ____ that attract neutrophils, eosinophils, and lymphocytes.
(Macrophages may also be infected by ____ released from the epithelium).
____ cell and ____ cell (not shown) immune responses also occur.
The epithelial cell that the rhinovirus entered triggers cytokines and innate immune response. Later, the adaptive response will kick in. Slow if first exposure, fast if subsequent. Look at the image and read text.
cytokines
rhinovirus
adaptive T
B
There are no ____ to treat Rhinovirus infection.
However, new drugs are being developed that will prevent Rhinovirus from binding to the the ____ receptor expressed on the surface of epithelial cells.
If we want to come up with a treatment for rhinovirus, the best method is to target rhinovirus binding to ICAM-1 (my interpretation: probably because it is more constant from one strain to the next since they all interact w/ the same receptor?)
drugs
ICAM
____ is the only “door” on the epithelial cell surface
that will allow rhinovirus to enter.
ICAM
How the viral canyon binds to cellular ICAM
• The inset on the right shows how a Rhinovirus is about to infect an epithelial cell.
• Below shows in greater detail how the ____ (or crevice) on the outer surface of the virus binds to the cell surface ____ receptor.
IMPORTANT: Rhinovirus recognizes the ICAM receptor because it has a ____. The canyon of the virus wants to meet the receptor.
What if we can block ICAM-canyon interaction?
Can’t see where he points on the slide, but it is labeled where ICAM/rhinovirus/canyon are.
canyon
ICAM-1
The ____ drug (being developed) binds the Rhinovirus Canyon.
The WIN will prevent Rhinovirus from
attaching to the cellular ICAM receptor on nasal epithelial cells
They are working on a drug with the geometry and conformation that sits inside the canyon. Goes back to previous slide to clarify that we are not trying to block/cover all ICAM receptors, but we are trying bind to the ____ itself to block the ICAM-canyon interaction.
WIN
rhinovirus
WIN binds the Rhinovirus Canyon
- To enter cells, Rhinovirus attaches to the cellular protein receptor, ICAM.
- For the virus to get into the epithelial cell, the ICAM protein needs to reach deep into a crevice
on the outer surface of the Rhinovirus, called the ____. - Antibodies against Rhinovirus neutralize the virus, also by binding to the ____.
- Drugs like WIN 52053 are being developed to work against the virus when there are no natural
antibodies to prevent Rhinovirus infection. WIN 52053 binds to the ____ of the viral Canyon to block binding by the cellular ICAM receptor
Understand labels of the receptor and virus surface in the image, this image is zoomed in to part of the virus surface.
Reads slide. WIN is being developed to work against all rhinoviruses, specially when you have no natural antibodies
canyon
canyon
floor
Summary Important Facts about Rhinovirus
• There are over160 strains of the virus.
Optimal replication occurs slightly below ____, which
is why rhinovirus replicates in the nasal passages and upper respiratory airway.
The virus is not ____, i.e., it does not enter the blood stream and does not cause a systemic infection.
The virus is transmitted by ____ (sneeze) or ____ contact.
____ is the cell receptor.
The many ____ of the virus have prevented development of a vaccine.
Antiviral approaches (e.g., ____ Drugs) are being developed.
body temperature viremic aerosol direct ICAM-1 strains WIN
KEY FEATURES of INFLUENZA VIRUS
• ____, minus strand, segmented ____ genome.
• Segmentation allows ____ in mixed infections.
• Pandemics occur several times in a Century due to ____.
• Yearly Epidemics are due to ____.
____ segmented strands, not one long strand.
Pandemic is everywhere, ____.
enveloped RNA random assortment antigenic shift antigenic drift 8 worldwide
Influenza virus has an RNA genome of ____ RNAs
Its envelope contains 2 important proteins: ____ and ____
- ____ is the only member
- The genome is made up of 8 RNA segments
- Each segments encodes either one or two proteins
- The virus is ____
RNA genome of 8 ____ RNA strands.
Know that the two important proteins of influenza are HA and NA (hemagglutinin and neuraminidase)
HA allows ____ into our cells. NA allows ____ from our cells after replication
8 HA NA influenza enveloped individual entry exit
HA and NA are on the ____ of the influenza virus
surface
Influenza ranks high amongst the viral respiratory diseases
Yay!
The incubation period for influenza is: ____ hours.
Adults with influenza remain infectious for:
____ days after onset of symptoms, and children may remain infectious for up to a ____ after onset.
Flu virus can survive ____ hours on a hard surface.
24-72
3-5
week
24
How bad is a flu outbreak?
Terminology used to define the epidemiology
____ - Very few cases
____ - > 2 but less than 50% the regions of a state
____ - > than 50% of the regions of a state
____ - More than 6.7% of deaths attributable to flu ____ - Worldwide epidemic
sporadic regional widespread epidemic pandemic
SEASONAL FLU
Of Note, as will be explained later, Seasonal Flu is due to small changes in the flu HA and NA genes, referred to as
____.
genetic drift
Flu is Seasonal: It Peaks from ____
Flu fluctuates with the time of year.
Early theory was that people are indoors more during the winter… probably not true
december to march
Why is Flu Infection Seasonal ?
Answer: It is due to low ____ and low ____: In regions that have a winter season, the influenza virus survives
____ in cold, dry air, so it has a greater chance of infecting another person*.
humidity
temperature
longer
Flu Map Dec 27, 2014
____ here
epidemic
Virus survives better when it is dry and when it is cold. It doesn’t ____ very easily through humid, thick, dense air in the summer.
move
