Unit 4 Flashcards
What is the name of the virus that causes mononucleosis?
EBV - Epstein-Barr Virus
Epstein-Barr Virus is part of what virus family?
The herpesvirus family
What 4 layers make up the EBV virus?
- nucleoprotein core 2. polyhedral capsis 3. tegument
4. envelope
What is the nucleoprotein core of EBV made up of?
DNA genome and proteins to fold it.
What is tegument?
It is the space between the capsid and envelope in EBV which contains 10-20 regulatory proteins
What are some examples of regulatory proteins?
Transcription factors and enzymes
What is unique about the envelope of the EBV virus?
in is roughly 150nm in diameter and contains up to 10 different spaces
What characteristics make up the genome of the EBV virus?
- linear dsDNA - up to 150 different proteins
2. not dependent on host cells for any DNA replication and has many proteins which regulate host cell activities
What is the reservoir for mononucleosis (EBV)?
- humans during infection: incubation through convalescence
- carriers who recover from mono produce virus periodically for life.
What are the 2 routes of transmission for mono?
- direct contact - saliva
2. fomites - saliva
What are the 2 primary types of cells infected by EBV?
- epithelial cells of nasopharynx and salivary glands
2. B lymphocytes
What are the three possible outcomes for EBV once it enters a host cell’s nucleus?
- can remain linear
- can become an episome (circular)
- can splice into chromosome
What are the 4 possible results of EBV infection?
- latent
- virus replication = lytic
- host cell replication with expression of some viral genes = mono
- host cell replication w/o expressing viral antigens = cancer
Where is the name “mononucleosis” derived from?
It is because mononuclear (lymphocytes) are proliferating
What are the outcomes of a lytic infection of EBV?
new viruses are being made and all viral genes are being expressed -> infectious. The symptoms here are roughly equivalent to that of a cold.
What happens to the nucleus of a host cell infected with EBV?
It becomes dimpled
What is occuring in an EBV infection resulting in mono?
no new viruses are being made, and only a few of the viral proteins are being expressed. The virus triggers infected B lymphocyte proliferation and random IgM antibodies are secreted by these infected B lymphocytes. Both B cells and CTL’s can attack infected B cells
How is it that EBV causes cancer?
Because the virus in this circumstance causes proliferation of the infected cells however no viral proteins are being expressed, so there is nothing to stop the proliferation
What are the two types of cancer that can occur as a result of EBV?
- B - cell lymphoma
2. nasopharyngeal carcinoma
What would put a person at risk for lymphoma?
A weakened immune system
Why are EBV infections in young children usually asymptomatic?
Because of the speed and intensity of their immune system
Why are 15-25 year old people most at risk for developing mononucleosis?
Because of their lifestyle which produces both weakened immune system and close proximities which promote transmission
What is the incubation period for mono?
4-7 weeks
Why is it that a person who has recovered from mono is likely a carrier for life?
Because if they have a latent form of the virus in their cells it can periodically become lytic with very little symptoms for the rest of their life.
What are the 3 most noteable symptoms of mononucleosis?
- a high and fluctuating fever
- sever pharyngitis
- lymphadenopathy
What is pharyngitis?
inflammation of the pharynx and nearby tonsils - possibly obstructing breathing
What is lymphadenopathy?
noticeable swelling of lymphocyte reservoirs (spleen and lymph nodes) due to lymphocyte proliferation
How long do the symptoms for mono generally last?
2-3 weeks
How long is the convalescence period for mononucleosis?
12-18 months
What are the 4 main complications that can arise from mononucleosis?
- ruptured spleen => internal bleeding
- Infection of other cell types => meningitis, encephalitis, carditis, nephritis, hepatitis or pneumonia
- B cell lymphoma (Burkitt’s lymphoma)
- Nasopharyngeal carcinoma
Why is it that the EBV is capable of infecting so many different types of cells in the body?
Because it has 10 spike proteins, so a receptor can be found almost anywhere
Why is it difficult to set a morbidity/mortality rate for mono?
Because it depends on where the person was infected
What is the morbidity rate of mononucleosis in developing countries?
<0.1%
What is the morbidity rate of mononucleosis in developed countries?
<10%
What is the incidence of mono in the U.S.?
1.5 million cases per year
What is the mortality rate of mono?
10/1.5 million, it is very rare
What is the mortality rate of B cell lymphoma?
10-70% dependent upon when it was detected and treatments available
What is the mortality rate of nasopharyngeal carcinoma?
50%
What are the 5 ways to diagnose mononucleosis?
- High mononuclear cell count
- lobed nucleus in lymphocytes - can be seen in blood smear
- prolonged prodromal symptoms
- look for heterophile antibodies
- antibodies being made by healthy B cells to EBV will be produced
What is the most general treatment of mono?
Simply rest
What medication is given for sever cases of mono?
acyclovir - base analog
What are the 2 behavioral preventions for mono?
- avoid the routes of transmission 2. expose kids when they are young
What can be done to prevent mono chemically?
acyclovir could be taken prophylactically, but normally wouldn’t be
What are the 2 current vaccine candidates against EBV?
- gp350 => spike protein
2. LMP2 => spike protein (naked DNA)
EBV is considered what type of carcinogen?
A class I carcinogen (the first human tumor virus)
What is the prevalence of EBV in adult populations worldwide?
> 90%
EBV is found in roughly 10% of all ________ cancers
stomach
Aside from EBV what other two herpesviruses have been linked to causing cancer?
- Human herpesvirus 8 (HHV8) also known as KSHV (kaposi sarcoma associated herpes virus)
- Human Papillomaviruses (HPVs)
What other viruses or infectious agents have begun to be associated with human cancer etiology?
- hepatocellular carcinoma viruses (hepatitis C and B)
- T cell leukemia virus (human T-lymphotropic virus I and II)
- Merkel cell carcinoma virus
It is estimated that overall ____ of all cancers are a result of infectious agents
1/5
In addition to being the first human cancer virus to be discovered, EBV was also….?
The first large herpesvirus genome to be completely sequenced
What do studies show may explain the variation in cancer risk from EBV?
polymorphisms
How many open reading frames does the EBV genome contain?
close to 100
What are the two proteins expressed consistently in human cancers that were found in EBV?
- EBV nuclear antigen (EBNA 1)
2. latent membrane protein (LMP 1)
How many microRNAs does the EBV genome code for?
over 20
Why are the expression of microRNA and other non-coding RNA’s in EBV significant?
Because they are expressed at high amount and have tumorigenic properties (including the potential to be transmitted via exosomes to noninfected neighboring cells
EBV latent infection is also capable of providing a mechanism for viral oncogenesis, why is this?
Because is epigenetically suppresses host tumor suppressor genes
What exactly does the gp350 vaccine target? Why is it not effective at reducing cancer associated with EBV?
It targets the glycoprotein of EBV, because it does not prevent the occurence of latent infection
How have B cell lymphomas arising from EBV been successfully treated?
Using adoptive immunotherapy
What types of selective treatments against EBV are currently being developed?
Biological and pharmacological inhibitors of viral proteins and oncongenes
What other diseases have been linked to EBV?
multiple sclerosis and lupus erythematosis
What type of vaccine would be ideal in defending against EBV related cancers?
A vaccine that stimulates a strong and selective T cell response to EBV-positive tumor cells
TB alone causes ____ of the deaths of AIDS patients
25%
What is the cause of multidrug=resistant TB?
overuse and misuse of antibiotics
TB is likely one of the most serious bacterial infections in the world today, how many people does it kill yearly?
about 2 million
What type of bacteria is responsible for tuberculosis?
Mycobacterium tuberculosis
When was Koch’s postulate first applied to tuberculosis?
In 1882
What are the 3 steps to Koch’s postulate?
- find a correlation because an microorganisms and disease
- test healthy subjects to see if they get the disease
- suggest a plausible mechanism for how this microorganism causes this disease
Is mycobacterium tuberculosis an aerobe, anaerobe, or facultative aerobe?
It is a strict aerbe
What is mycolic acid made up of?
It is made up of hydrocarbons, it is non-polar
What are the 5 forms of defense that mycolic acid provides?
- resistant to many disinfectants
- resistant to dessication
- resistant to most antibiotics
- resistant to lysosomal enzymes
- relatively non-immunogenic (because it covers antigens
What is the generation time for tuberculosis?
18-24 hours
Which type of immunity is useless against TB?
humoral
What is the reservoir for TB?
primarily humans, with acute or active TB
Which countries have the largest reservoir of TB?
South Africa, Russia, China, India, and North Korea
What is the R0 for TB?
3
What are the routes of transmission for TB?
- direct contact -> coughing and speaking
- vehicle -> airborne (can remain airborne for a while)
- fomites, sometimes
What are some co-factors for TB?
- dense housing
- poor nutrition
- poor healthcare systems
Who are some of the susceptible hosts for TB?
AIDS, homeless, immigrants and refugees, prison inmates
What is the portal of entry for Mycobacterium?
Respiratory, they are inhaled
What is the first thing that happens to M. tuberculosis after they are inhaled?
They are quickly phagocytosed by macrophages in the alveoli.
How are M. tuberculosis able to survive phagocytosis?
They are able to survive because of their mycolic acid layer.
What do the M. tuberculosis bacteria do as soon as they escape the phagosome?
They multiply in the cytoplasm of the macrophages.
What type of cell is the first to be damaged by the M. tuberculosis bacteria?
Macrophages
What is the consequence of the damage being done to the macrophages?
Inflammation occurs, and neutrophils and monocytes are brought in as a result, acute pneumonia could occur here (however at this point recovery is still possible and 40% are asymptomatic
What is a tubercle?
It is the name given to the fibrous/CT wall (also known as a granuloma) that the macrophages form around the M. tuberculosis when they are unable to eliminate them. They do this in order to restrict their spread.
Why is the tubercle effective at restraining the Mycobacterium tuberculosis?
Because they create a 1. acidic environment 2. anaerobic environment and 3. low nutrient supply
What is a TB infection called when the Mycobacterium tuberculosis bacteria are all trapped inside of tubercles?
It is a latent infection
____ of the world has latent TB
1/3
How could latent TB become an activated?
If the body defenses become weakened (by things like stress, AIDS, age, immune system suppression, etc.) latent TB can escape the tubercles and become active TB
What are the 3 major consequences following the rupture of a tubercle?
- the infected area in the lung enlarges
- inflammation occurs, this results in fluid accumulation and therefore a decreased oxygen supply and a reflexive cough.
- the bacteria are able to spread due to coughing
What are two complications that can present themselves as a result of an active TB infection?
- bacteria can enter the bloodstream and spread to pleura, pericardium, kidneys, bones, joints, and the CNS
- scar tissue that is left after recovery results in less oxygen capacity
What is the incubation period for TB?
2-10 weeks
What is the convalescence for TB?
approximately 6 months
How many cases of latent TB are there in the U.S. alone?
15 million, but only 10,000 active cases
How many deaths does TB cause worldwide each year?
approximately 2 million
What is the morbidity rate for latent TB?
60%
What is the morbidity rate for active TB?
10% worldwide, 0.1% in the U.S.
What is the mortality rate for TB in the U.S. with treatment?
approximately 5%
What is the mortality rate for TB world-wide with treatment?
approximately 17%
What is the mortality rate for untreated TB?
approximately 50%
What is the Mantoux test?
It is a tuberculin skin test. 1. a very small about of M. tuberculosis protein extract is injected 2. if the person has been exposed (active, latent, immunization) then macrophages will accumulate 3. this results in a firm, red swelling to appear after 48 hrs.
Why do macrophages in the Mantoux test accumulate?
Because the TB antigens injected stimulate memory T helper cells which then secrete interferon, the interferon is what signals the macrophages and causes them to accumulate
How does the TB blood test = gamma release assay work?
- monocytes are collected from the patients blood sample and expose to TB proteins in a culture
- If monocytes have been exposed before, they will secrete IFN - gamma
- The IFN - gamma concentration can then be measured
What are 2 major advantages to the TB blood test over the mantoux test?
- It is only sensitive to people who have actually been exposed to the infection and not to people who have been vaccinated
- It gives quick results
How is a chest x-ray useful in diagnosing TB?
It allows for tubercles to be identified. It can also show scar tissue as well
What is sputum staining in TB diagnosis?
It is “acid-fast” staining -> the sample is boiled, which melts the wax of the M. tuberculosis, stain is then able to enter into the cell. Cooling it allows for the wax to harden again, trapping the stain inside. The slide is then rinsed with 95% ethanol and 3% HCl, at this point only M. tuberculosis will be stained and visible
What is the advantage to sputum sampling in diagnosing TB?
It is very sensitive. Even if you just have a single bacteria, it can grow into a colony and be observed
What is the disadvantage to sputum sampling in diagnosing TB?
It takes a really long time (3-6 weeks). This is due to the long generation time of TB.
How can PCR be used to diagnose TB?
Amplifying TB genes will allow you to know for certain that you have TB. Also, it would allow for the detection of resistance genes
What is the fluorophage test?
Researchers designed a phage which infects only TB cells, injecting a gene known as GFP when it does. The GFP gene then uses the bacteria’s ATP to glow green allowing for the observation and detection of M. tuberculosis
What was the treatment used for TB before a useful antibiotic was discovered?
The patients were placed in sanitaria. These are places with lots of good food and fresh air, the patients were to sleep outside as much as possible. This treatment actually cured 30% of patients
How is active TB treated with antibiotics?
- first with a combination of 4 antibiotics for 2 months
2. then with a combination of 2 antibiotics for 4-7 mons
How is latent TB treated?
With isoniazid (which inhibits mycolic acid synthesis) for 9 months
Why is TB treatment so long?
Because most of the drugs are targeting replicating bacteria and therefore inactive drugs are unaffected and drugs need to be available for whenever they are activated.
What is the DOTS program?
directly observed therapy short-course. It is a program developed by WHO to ensure that TB patients take their antibiotic treatments and carry them out to completion.
What can be done behaviorally to prevent TB?
Screening
What can be done chemically to prevent TB?
1-2 antibiotics can be given to close contacts of an infected person
Why is the BCG vaccine for TB not used in the U.S.?
Because it is less safe, not particularly effective, and it obscures screening
What is in the TB vaccine that exists?
a weakened live Mycobacterium bovis
What is the name of the common influenza strain in the US?
H3N2
Which influenza virus associated with swine flu?
H1N1
What is the influenza virus associated with bird flu?
H5N1
How many H protein and N proteins have been found that are associated with influenza strains?
16 H’s and 9 N’s
What is the morbidity rate for influenza, seasonal flu?
10-40%
What is the mortality rate?
Most strains (H3N2) around 0.1%, however bird flue H5N1 is <50%
What is hemadsorption? and how is it used to diagnose influenza?
Influenza virus when it infects mammalian cells causes them to express H and N proteins, RBC’s bind to H protein, therefore if influenza virus is present you will see a ring of red blood cells
What does H stand for in the H protein?
hemagglutinin
What is the effect of taking Tamiflu when you have influenza?
It reduces the symptoms from 7 to 5 days in duration
What is the mode of action of Tamiflu against the influenza virus?
It is a nuraminidase inhibitor
What is the mode of action of amantadine against the influenza virus?
It is a H+ channel blocker. It is however only 50% effective and has been known to cause CNS problems
What is the newest treatment discovered against influenza (still experimental)?
arbidol, it works by blocking H proteins
What are the 5 ways to prevent influenza?
- inactivated virus vaccine - stimulates IgG with acts to neutralize the virus
- attenuated virus vaccine - nasal spray with causes a small scale infection leaving you with memory cells as a result
- prophylactic tamiflu
- prophylactic amantidine
- quarantine, both individual as well as communal
what is the shape of the dengue virus capsid?
polyhedral
What is the purpose of the hairpin loop on the 3 prime end of the ssRNA in the dengue virus?
It provides it protection from exonucleases
What are the 3 reservoirs for dengue?
- humans
- primates
- mosquitos
Why are mosquitos considered both a reservoir and a route of transmission?
Because the viruses multiply inside of the mosquito, but they also escape the mosquito through a mosquito bite
What type of mosquito is the carrier for dengue?
Aedes aegypti
Where did dengue originate?
South East Asia
Even thogh dengue does not usually spread from person to person, there are 4 exceptions, what are they?
- blood transfusion
- organ transplant
- blood left on needle stick
- can cross the placenta
What are the 5 primary ways to diagnose dengue?
- PCR on blood sample
- test for antigens using antibodies
- test for antibodies using antigens
- unique symptoms
- turniquet test
Dengue is endemic in more than _____ countries
100
How many people are at risk for dengue?
2.5 billion people
What is the morbidity rate of dengue?
4-12%
How many dengue cases generally need to be hospitalized?
0.5%
What is the mortality rate of dengue?
2.5%
Why are there no antiviral drugs for dengue?
Because all we have is the one for HIV and the protease inhibitors don’t work on Dengue virus
Analgesics can be prescribed for the pain, but ibuprofen and aspirin should not be used. Why?
Because they are blood thinners, and they could enhance the possibility of acquiring dengue shock syndrome
Why is oral rehydration used to treat dengue?
So that the blood volume is maintained despite all of the inflammation
What 5 behavioral preventions can be taken against dengue?
- eradication of mosquito breeding sites
- introduce fish which eat mosquito larvae
- remove water puddles
- destroy/recycle old tires
- prohibit water-collection barrels
What is a chemical prevention method against dengue?
bed nets treated with DEET
Why is difficult to develop a vaccine for dengue??
Because it would have to target all 4 serotypes of dengue
What is contained in the leading candidate for a dengue vaccine?
attenuated yellow fever virus and dengue virus spikes.
What does ADE stand for?
Antibody - dependent enhancement
