[04.01b] Oncogenic Viruses (Part 2) V2.1.pdf

virion, genome, replication, and pathology

What four specific characteristics of the viruses should be known, according to the learning objectives?

spherical, 100-200nm, dsDNA, linear

What are the general characteristics of the Herpesviridae virion?

Larger

How does the size of Herpesviridae compare to polyomaviridae and papillomaviridae?

35

Approximately how many proteins are produced by Herpesviridae?

dsDNA

Why does Herpesviridae produce a large number of proteins?

(+)

Does Herpesviridae have an envelope?

Fc receptor

What receptor is associated with the envelope of Herpesviridae?

nucleus

Where does Herpesviridae replication occur within the host?

lytic and latent life cycle

What is the unique characteristic of the Herpesviridae life cycle?

active viral replication

What occurs during the lytic life cycle?

no viral replication

What occurs during the latent life cycle?

location of lytic and latent life cycle

What is the basis for the classification of Herpesviridae?

Alphaherpesvirinae, Betaherpesvirinae, Gammaherpesvirinae

What are the three subfamilies of Human Herpesviruses (HHV)?

Epstein-Barr Virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV)

Which two HHV species are oncogenic?

short and cytolytic

What is the growth cycle and cytopathology of Alphaherpesvirinae?

neuron

Where does Alphaherpesvirinae hide during latent infection?

Genus Simplex and Genus Varicella

What are the two genera belonging to Alphaherpesvirinae?

Herpes simplex virus type 1 (HSV-1)

What is AKA HHV-1?

blisters on the face

What is the lytic cycle manifestation of HSV-1?

trigeminal nerve

Where does HSV-1 hide during its latent cycle?

immunocompromised

In what type of patient does the lytic cycle of HSV-1 often return with visible blisters?

Herpes simplex virus type 2 (HSV-2)

What is AKA HHV-2?

genital mucosa

What does HSV-2 infect during its lytic cycle?

Varicella-zoster virus (VZV)

What is AKA HHV-3?

chickenpox (varicella)

What is the primary infection manifestation of VZV?

shingles (herpes zoster)

What is the re-infection manifestation of VZV?

immunocompromised adults

What patient population is typically infected by shingles?

neurons

Where does VZV hide during its latent cycle?

dermatomal

What type of infection is shingles?

long and cytomegalic

What is the growth cycle and cytopathology of Betaherpesvirinae?

Massive enlargement of the infected cells

What does cytomegalic cytopathology result in?

glands, kidneys, or lymphoid tissues

Where does Betaherpesvirinae hide during latent infection?

Cytomegalovirus (CMV)

What virus is AKA HHV-5?

glands and kidneys

Where does CMV hide during latent infection?

human herpesvirus 6 (HHV-6)

What is the common name/AKA for the Roseola genus?

long and lymphoproliferative

What is the growth cycle and cytopathology of the Roseola genus (HHV-6)?

lymphoid tissues

Where does HHV-6 hide during latent infection?

variable and lymphoproliferative

What is the growth cycle and cytopathology of Gammaherpesvirinae?

targets B cells and T cells

What does lymphoproliferative cytopathology mean for Gammaherpesvirinae?

lymphoid tissues (e.g. spleen)

Where does Gammaherpesvirinae hide during latent infection?

Genus Lymphocrypto and Genus Rhadino

What are the two oncogenic genera of Gammaherpesvirinae?

Epstein-Barr Virus (EBV) or HHV-4

Which oncogenic species belongs to the Genus Lymphocrypto?

Kaposi sarcoma-associated herpesvirus (KSHV) or HHV-8

Which oncogenic species belongs to the Genus Rhadino?

Infectious Mononucleosis (Kissing disease or “mono”)

What is the primary infection caused by EBV?

sore throat, skin rash, lymph enlargement

What are three symptoms of Infectious Mononucleosis?

mumps (beke)

Infectious Mononucleosis symptoms are sometimes mistaken for what other disease?

2-4 weeks

How long after infection is the EBV lytic phase typically cleared?

B cells

Where does EBV primarily hide during latent infection?

Nasopharyngeal carcinoma and Gastric carcinoma

What two cancers result if EBV reactivation occurs in epithelial cells?

Hodgkin’s lymphoma, Non-hodgkin’s lymphoma, Burkitt’s lymphoma

What three B cell cancers are associated with EBV reactivation?

T cell lymphoma

What is a very seldom B cell or T cell cancer associated with EBV?

HIV patients or transplant patients

In what two patient populations are EBV-related lymphoproliferative disorders often seen?

saliva and semen

What are two bodily fluids through which EBV is transmitted?

oropharynx

What is the entry point of EBV?

Adsorption, Penetration, Replication in the nucleus, Release of the virus

What are the usual steps of the lytic phase?

Viral persistence, Restricted expression, Potential for reactivation, Cell markers (Latent cell antigens)

What are the four hallmarks of herpesviridae latency?

capsid proteins and glycoproteins

What specific proteins are not expressed during the restricted expression phase of EBV latency?

germinal center

Where does EBV hide initially before potential reactivation?

viral envelope glycoprotein gp350

What is the viral target protein that interacts with the B cell during EBV adsorption?

CD21 (or CR2) receptor

What B cell receptor does EBV gp350 interact with?

C3d complement

What other substance binds to the CD21 receptor?

episome

What does the EBV virus create inside the cell (a genetic element outside the host chromosome)?

LMP 1, EBNA 2, and EBER 3

What are three important viral antigens produced inside the nucleus by EBV?

B cell immortalization

What is the importance of EBV viral antigens?

germinal centers (spleen, lymph nodes)

Where do immortalized B cells go to hide from T cells?

chemical-inducing agents or antibodies cross-linking with EBV

What two factors can trigger EBV to exit latency and enter the lytic cycle?

memory B cells

What type of B cells enter the latent cycle and become immortalized?

EBNA (EBV nuclear antigens)

Which latent phase EBV antigen changes the MHC protein so it won't be presented to T cells?

DNA episomes

EBNA is associated with what form of EBV DNA?

LMP (latent membrane protein)

Which latent phase EBV antigen mimics growth factor and is important for transformation?

EBER (EBV-encoded small untranslated RNA)

Which EBV antigen is present in both latent and lytic phases?

non-structural proteins

What characterizes Early Antigens (lytic phase)?

Onset of viral replication

What does the presence of Early Antigens signify?

Viral capsid antigen and Viral envelope glycoprotein

What are two examples of Late Antigens (lytic phase)?

Productive replication

What does the presence of Late Antigens signify?

subclinical and self-limiting

How is Infectious Mononucleosis characterized in terms of clinical outcome?

90%

According to a study, what percentage of the population is seropositive for EBV?

Body aches, fatigue, fever, swollen tonsils

What are four symptoms of Infectious Mononucleosis?

fluids and bed rest

What is the recommended treatment for Infectious Mononucleosis?

Burkitt’s lymphoma

What is a tumor of the jaw prevalent in African children resulting from latent infection reactivation?

Epstein-Barr virus nuclear antigen 1 (EBNA1)

Which EBV antigen can be isolated in 90% of Burkitt’s lymphoma patients in Africa?

Malaria

What is a cofactor for Burkitt’s lymphoma in Africa?

preponderance of B-cells

Why is Malaria considered a cofactor for Burkitt’s lymphoma?

activation of proto-oncogene c-myc

What is the main genetic translocation involved in Burkitt’s lymphoma?

Chinese, Southeast Asian descent, or Eskimos

What three populations usually exhibit Nasopharyngeal Carcinoma?

High diet of salted and dried fish

What is a possible cofactor for Nasopharyngeal Carcinoma?

Oral Hairy Leukoplakia

What pathology looks like Candidiasis but has white patches that cannot be removed?

EBV actively replicating in epithelial cells

What causes Oral Hairy Leukoplakia?

poor prognosis

What does Oral Hairy Leukoplakia signify if an AIDS patient has it?

Not pre malignant

Is Oral Hairy Leukoplakia considered premalignant?

50%

What percentage of Reed Sternberg cells in Hodgkin’s Lymphoma have the EBNA or EBV antigen?

20-40 years old

What is the age range for Hodgkin’s Lymphoma patients?

100%

What percentage of CNS non-Hodgkin’s lymphoma cases virtually have the virus?

uncontrolled production of lymphocytes

What characterizes other lymphoproliferative disorders?

PCR

What laboratory diagnostic test for EBV can detect EBV DNA in the blood and check the progression of PTLD?

Serology

What method involves the detection of antibodies for EBV antigens?

ELISA, Immunoblot, Heterophile agglutination test

What three specific tests are used for EBV serology?

heterophile antibody

What antibody does the Heterophile agglutination test detect?

Monospot test

What is an example of a quick heterophile agglutination test used in the US for infectious mononucleosis?

Acyclovir

What antiviral drug can stop EBV from actively replicating?