Herpesviruses EBV, CMV, HHV6, HHV8, and Prions

Question 1

Remember, all herpes viruses are _____ viruses

Answer 1

DNA viruses

Question 2

All herpes viruses have what type of replication cycle?

Answer 2

Have an immediate-early, early, and late replication cycle and are all enveloped

Question 3

How are all herpes viruses killed?

Answer 3

Can be killed by detergents, heat, drying, and acids

Question 4

How is Epstein-Barr Virus (EBV) transmitted?

Answer 4

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

Question 5

EBV establishes latency in ______

Answer 5

memory B cells

Question 6

What happens when children are infected with EBV?

Answer 6

-Children infected usually have subclinical or mild disease
-Adolescent/young adults, 50% of infected will get infected mononucelosis

Question 7

The mononucleosis virus initially divides in the ____ causing…..

Answer 7

oropharynx, causing a sore throat through lytic infection. It then infects its main target, B-cell

Question 8

EBV mononucleosis is known as _________

Answer 8

heterophile antibody-positive mononucleosis

Question 9

EBV’s infection causes generalized activation of B cells; this, in turn, will lead to….

Answer 9

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

Question 10

What is the primary cause of symptoms of mononucleosis?

Answer 10

The massive expansion of cytotoxic T lymphocytes (to contain EBV+ B cells) and their associated cytokines

Question 11

Infectious Mononucleosis has a (short/long) incubation time

Answer 11

LONG - about 4-6 weeks, and the virus can be shed in the saliva before symptoms start

Question 12

What happens once the acute infection of mononucleosis is over?

Answer 12

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

Question 13

T/F: EBV can reactivate from the memory B cell pool and make new infectious virus

Answer 13

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.

Question 14

List some complications of Mononucleosis

Answer 14

-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

Question 15

What is Oral Hairy Leukoplakia (OHL)?

Answer 15

A benign, non-painful lesion on the later border of the tongue

Question 16

What increases the chance of developing OHL?

Answer 16

smoking

Question 17

Can OHL be scraped off the tongue?

Answer 17

NO

Question 18

OHL can be the first sign that someone has an ______ infection

Answer 18

HIV

-or occur in people taking immunosuppressive drugs

Question 19

Can OHL occur in immunocompetent people?

Answer 19

Yes, but it is rare

Question 20

How do you treat OHL?

Answer 20

-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.

Question 21

List the EBV cancers

Answer 21

-Nasopharyngeal carcinoma
-Burkitt Lymphoma (BL)

Question 22

What causes Nasopharyngeal carcinoma?

Answer 22

EBV but also unknown cofactors (possibly genetics, diet, other chemical exposures, and HLA type)

Question 23

Where are most nasopharyngeal carcinoma cases foud?

Answer 23

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.

Question 24

Does a person survive Nasopharyngeal carcinoma?

Answer 24

There is a good chance of survival with tx if caught early enough, but it can reoccur

Question 25

What is Burkitt Lymphoma (BL)?

Answer 25

-Very fast-growing, aggressive cancer -Is EBV-associated

Question 26

In parts of central Africa, ____ is the causative agent in endemic Burkitt lymphoma and has a high incidence

Answer 26

EBV (In the US, sporadic BL can be EBV-associated but only in a low percentage of cases)

Question 27

What causes BL?

Answer 27

-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

Question 28

Where is endemic BL usually seen? Sporadic BL?

Answer 28

-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

Question 29

How is Cytomegalovirus (CMV) transmitted?

Answer 29

-Via saliva, urine, blood, breast milk, semen, and cervical secretions. -It can be spread through sexual contact, contact with infected saliva, urine, and breastfeeding

Question 30

Is it possible to be infected with more than one strain of Cytomegalovirus?

Answer 30

Yes, there are many different strains of CMV

Question 31

Where does CMV establish latency?

Answer 31

Latency is established in myeloid precursor cells in the bone marrow

Question 32

What cells does CMV infect?

Answer 32

Infects a wide range of cells

Question 33

CMV can be severe in _______ people

Answer 33

immunocompromised -In people with AIDS, retinitis is the most frequent problem with CMV -CMV is a significant problem in transplant patients

Question 34

Most CMV infections are asymptomatic. What are the exceptions?

Answer 34

-CMV mono-like syndrome -Congenital infections -Immunocompromised

Question 35

Describe Mononucleosis like-syndrome (heterophile antibody-negative mono)

Answer 35

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.

Question 36

What is the #1 congenital infection in the US?

Answer 36

Congenital CMV

Question 37

T/F: During pregnancy, primary CMV infection has a high risk of transferring CMV to the fetus

Answer 37

TRUE The risk of congenital CMV from an already CMV-positive woman is low

Question 38

What do babies born with asymptomatic CMV infections have a risk of?

Answer 38

10% risk of some hearing loss. This hearing loss can be delayed or progressive

Question 39

What do babies born with symptomatic CMV infection have a risk of?

Answer 39

These babies can have motor and cognitive deficits, hearing loss, or vision impairment. They generally have more sequelae than babies born with asymptomatic infection

Question 40

Are CMV infections that are acquired AT birth or through breastfeeding a problem?

Answer 40

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.

Question 41

Where do many children get CMV infections?

Answer 41

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.

Question 42

_____ is a very common childhood infection

Answer 42

HHV6

Question 43

HHV6 is the cause of ________

Answer 43

Roseola and febrile seizures

Question 44

HHV8 (Kaposi sarcoma-associated herpesvirus) is present in large numbers in _______ but lower in the ________

Answer 44

MSM; general population of the US

Question 45

List the symptoms of HHV8

Answer 45

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

Question 46

How is HHV8 transmitted?

Answer 46

Probably transmitted through sex and/or saliva/kissing

Question 47

Describe the lesion presentation of HHV8

Answer 47

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)

Question 48

Why was the term 'Prion' coined?

Answer 48

To highlight the fact that it was a proteinaceous infectious particle

Question 49

What is a prion?

Answer 49

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

Question 50

The PrPsc has a high number of ______ compared to PrPc

Answer 50

beta-sheets

Question 51

How does an infectious PrPsc work?

Answer 51

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.

Question 52

How are the different kinds of prion diseases caused?

Answer 52

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.

Question 53

What are the vast majority of prion disease?

Answer 53

Spontaneous Creutzfeldt-Jacob disease This is primarily seen in older people

Question 54

What is the life expectancy of someone with prion disease?

Answer 54

After symptoms appear, life expectancy is rarely over a year. It is a fatal condition

Question 55

T/F: It is very easy to kill prion proteins

Answer 55

False! Prions are resistant to many disinfectants, proteases, and normal autoclaving. It is very hard to kill prion proteins

Question 56

What causes vCJD (variant Creutzfeldt-Jacob Disease)

Answer 56

Caused by eating beef contaminated with prion proteins (Incubation time could be as short as 5 years and is still 100% fatal)

Question 57

What is the cause of Iatrogenic Creutzfeldt-Jacob Disease (iCJD)

Answer 57

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.