Herpesviruses EBV, CMV, HHV6, HHV8, and Prions Flashcards
Remember, all herpes viruses are _____ viruses
DNA viruses
All herpes viruses have what type of replication cycle?
Have an immediate-early, early, and late replication cycle and are all enveloped
How are all herpes viruses killed?
Can be killed by detergents, heat, drying, and acids
How is Epstein-Barr Virus (EBV) transmitted?
through saliva
(Mono is known as ‘the kissing disease’)
*By 35-40 years of age, almost all people in the US are infected
*People sporadically shed virus in saliva throughout life after they’re infected
EBV establishes latency in ______
memory B cells
What happens when children are infected with EBV?
-Children infected usually have subclinical or mild disease
-Adolescent/young adults, 50% of infected will get infected mononucelosis
The mononucleosis virus initially divides in the ____ causing…..
oropharynx, causing a sore throat through lytic infection. It then infects its main target, B-cell
EBV mononucleosis is known as _________
heterophile antibody-positive mononucleosis
EBV’s infection causes generalized activation of B cells; this, in turn, will lead to….
heterophile antibody production
Heterophile antibodies are non-specific antibodies that will react with certain animals, horses, and sheep, RBC. A test for the presence of these antibodies is called the monospot test
What is the primary cause of symptoms of mononucleosis?
The massive expansion of cytotoxic T lymphocytes (to contain EBV+ B cells) and their associated cytokines
Infectious Mononucleosis has a (short/long) incubation time
LONG - about 4-6 weeks, and the virus can be shed in the saliva before symptoms start
What happens once the acute infection of mononucleosis is over?
Some memory B cells have the latent EBV genome. They maintain their latency w/o producing any proteins. When the B cells divide, they express a viral protein to make sure the viral genome goes into both cells
T/F: EBV can reactivate from the memory B cell pool and make new infectious virus
TRUE - the virus will go back to the oropharynx and infect epithelial cells. These EBV-infected epithelial cells will produce virus that can then be detected in saliva.
This will occur sporadically throughout an infected person’s life.
List some complications of Mononucleosis
-Rupture of the spleen can occur (the spleen is enlarged making it more fragile)
-Mild hepatitis can occur
-Can cause airway obstruction due to enlarged tonsils
What is Oral Hairy Leukoplakia (OHL)?
A benign, non-painful lesion on the later border of the tongue
What increases the chance of developing OHL?
smoking
Can OHL be scraped off the tongue?
NO
OHL can be the first sign that someone has an ______ infection
HIV
-or occur in people taking immunosuppressive drugs
Can OHL occur in immunocompetent people?
Yes, but it is rare
How do you treat OHL?
-Certain drugs or acyclovirs can be taken to clear lesions, but the lesions usually come back within a few weeks of treatment cessation.
-It is best to start antiviral drugs for HIV. OHL will most likely clear up when the CD4 count increases.
List the EBV cancers
-Nasopharyngeal carcinoma
-Burkitt Lymphoma (BL)
What causes Nasopharyngeal carcinoma?
EBV but also unknown cofactors (possibly genetics, diet, other chemical exposures, and HLA type)
Where are most nasopharyngeal carcinoma cases foud?
It is rare in the US, and cases are often found in recent immigrants from certain parts of Africa, some Asian countries, and the native populations of Alaska and Canada.
Does a person survive Nasopharyngeal carcinoma?
There is a good chance of survival with tx if caught early enough, but it can reoccur
What is Burkitt Lymphoma (BL)?
-Very fast-growing, aggressive cancer
-Is EBV-associated
In parts of central Africa, ____ is the causative agent in endemic Burkitt lymphoma and has a high incidence
EBV
(In the US, sporadic BL can be EBV-associated but only in a low percentage of cases)
What causes BL?
-A chromosomal translocation of the c-myc gene to a chromosome that has an immunoglobulin locus.
-This causes unregulated c-myc expression resulting in uncontrolled cell growth
Where is endemic BL usually seen? Sporadic BL?
-Endemic BL generally starts as a tumor of the facial or jawbone. eBL is more likely to be in young children (4-7 y/o)
-Sporadic BL in the US usually starts in the abdomen, not the jaw.
*Immunosuppression can increase the chance that EBV is associated with sporadic BL, and EVB-associated BL is higher in people living with HIV
How is Cytomegalovirus (CMV) transmitted?
-Via saliva, urine, blood, breast milk, semen, and cervical secretions.
-It can be spread through sexual contact, contact with infected saliva, urine, and breastfeeding
Is it possible to be infected with more than one strain of Cytomegalovirus?
Yes, there are many different strains of CMV
Where does CMV establish latency?
Latency is established in myeloid precursor cells in the bone marrow
What cells does CMV infect?
Infects a wide range of cells
CMV can be severe in _______ people
immunocompromised
-In people with AIDS, retinitis is the most frequent problem with CMV
-CMV is a significant problem in transplant patients
Most CMV infections are asymptomatic. What are the exceptions?
-CMV mono-like syndrome
-Congenital infections
-Immunocompromised
Describe Mononucleosis like-syndrome (heterophile antibody-negative mono)
CMV does not cause the activation of B cells but a substantial activation of T cells. Because it does not infect B cells, there will be no generalized activation of antibodies and no production of heterophile antibodies. It will be heterophile antibody negative and, thus, monospot negative.
What is the #1 congenital infection in the US?
Congenital CMV
T/F: During pregnancy, primary CMV infection has a high risk of transferring CMV to the fetus
TRUE
The risk of congenital CMV from an already CMV-positive woman is low
What do babies born with asymptomatic CMV infections have a risk of?
10% risk of some hearing loss. This hearing loss can be delayed or progressive
What do babies born with symptomatic CMV infection have a risk of?
These babies can have motor and cognitive deficits, hearing loss, or vision impairment. They generally have more sequelae than babies born with asymptomatic infection
Are CMV infections that are acquired AT birth or through breastfeeding a problem?
Unless a baby is a very low birth weight or is immunosuppressed, infections that are acquired at birth or
through breastfeeding are not a problem.
Where do many children get CMV infections?
Many children in daycare get CMV infections and can secrete CMV in urine and saliva for over a year. Children can be a major cause of adult infection. Remember, most infections are asymptomatic.
_____ is a very common childhood infection
HHV6
HHV6 is the cause of ________
Roseola and febrile seizures
HHV8 (Kaposi sarcoma-associated herpesvirus) is present in large numbers in _______ but lower in the ________
MSM; general population of the US
List the symptoms of HHV8
It usually causes no symptoms unless co-infected with HIV.
People with co-infections have a risk of developing Kaposi sarcoma. The risk increases with a lower CD4 count. With an aging population infected with HIV, Kaposi’s sarcoma can be seen with higher CD4 counts
How is HHV8 transmitted?
Probably transmitted through sex and/or saliva/kissing
Describe the lesion presentation of HHV8
Oral lesions are often seen with Kaposi sarcoma, along with lesions on other parts of the body. KS lesions are often violet but can change to a brown color. (The lesion progresses from patch to plaque and finally to nodular)
Why was the term ‘Prion’ coined?
To highlight the fact that it was a proteinaceous infectious particle
What is a prion?
It is only a protein, nothing else
The prion protein is a normal protein found in the brain. The infectious prion is a misfolded prion protein. The normal protein is referred to as PrPc, and the misfolded infectious protein is referred to as PrPsc
The PrPsc has a high number of ______ compared to PrPc
beta-sheets
How does an infectious PrPsc work?
The infectious PrPsc converts the cells PrPc
into an altered form
(PrPsc), causing aggregates that form amyloid plaques. The
aggregates that form with the misfolded proteins cause the
cell to die, releasing the infectious misfolded prion protein. This PrPsc goes on to other cells and converts their PrPc protein to the misfolded form. This leads to the spongiform appearance of parts of the brain.
How are the different kinds of prion diseases caused?
All caused by misfolding of the prion protein
There is no genetic
component and no infection. It is just a spontaneous mutation in the prion gene or a spontaneously
misfolded protein that becomes ‘infectious’ to the normal prion proteins in the brain.
What are the vast majority of prion disease?
Spontaneous Creutzfeldt-Jacob disease
This is primarily seen in older people
What is the life expectancy of someone with prion disease?
After symptoms appear, life expectancy is rarely over a year. It is a fatal condition
T/F: It is very easy to kill prion proteins
False! Prions are resistant to many disinfectants, proteases, and normal autoclaving. It is very hard to kill prion proteins
What causes vCJD (variant Creutzfeldt-Jacob Disease)
Caused by eating beef contaminated with prion proteins
(Incubation time could be as short as 5 years and is still 100% fatal)
What is the cause of Iatrogenic Creutzfeldt-Jacob Disease (iCJD)
These cases are from a healthcare setting. Most cases are from material harvested from cadavers. **Some infections were caused by using prion-contaminated neurosurgical instruments. Dental instruments that come in contact with nerve tissue could potentially be contaminated with prions if not cleansed properly.
