49 terms

Infectious mononucleosis

Infectious mononucleosis
"kissing disease"
signs/symptoms: Burkitt's lymphoma
EBV and Cytomegalovirus
EBV Family
Herpes viridae
EBV Subfamily
EBV Genus
EBV Species
Human herpes virus 4 (Epstein Barr Virus)
EBV Structure
Capsid: Icosahedral
Genome: dsDNA, linear
Enveloped: yes
What's EBV cause?
Heterophile positive infectious mononucleosis (mono or kissing disease)
may be asymptomatic or vary in severity;
common: 70% of US population will be infected by age 30; 90% of world has been infected by EBV;
35-50% during adolescence or young adulthood;
lifelong latent infection in some immune cells;
Burkitt's lymphoma and nasopharyngeal carcinoma can occur (not common in US) tho not sole cause
Burkitt's lymphoma
aka B cell lymphoma
seen in equatorial Africa; related to EBV infection in 95% cases;
disease has a high chance of involving the jawbone
How to know if you have infectious mononucleosis
milder in children (normally asymptomatic) than adults
typically seen in 15-17 year olds; symptoms include:
traid of lymphadenopathy, fever and exudative pharyngitis lasting for 1-4 weeks
can be accompanied by malaise, splenomegaly, and often hepatosplenomegaly
ampicillin-induced rash
most ppl get better in 2-4 weeks; may feel tired for a few months
What happens with EBV?
EBV can cause recurring disease in some ppl;
EBV infects B cells & epithelial cells of the oropharynx promoting virus shedding into saliva to transmit to others;
Cytotoxic T cells attack these infected B cells and kill them; This attack gives the symptoms of mono (sore throat, fever, fatigue, splenomegaly, ect)
EBV can cause mono, latency or cancer.
Consequence of EBV infection
1. replicate in B cells/epithelial cells
2. cause latent infections of B cells
3. stimulate and immortalize B cells
Lymphoproliferative diseases
generally seen in immunocompromised hosts;
Burkitt's lymphoma is seen in malaria endemic regions of equatorial Africa and accounts for 1/2 of all childhood cancers.
- related to EBV ~100% cases (all tumor cells + for EBV DNA)
- disease has high chance of involving jawbone
Burkitt's lymphoma symptoms
lymph node swelling (neck, arms, groin)
night sweats
abdominal pain
unexplained weight loss
itchy skin
Diagnosis of Burkitt's lymphoma
by symptoms
presence of neutropenia (decrease in neutrophils)
histology (large, lobed B lymphocytes w/atypical nuclei)
lymph node biopsy
Burkitt's lymphoma
multi-step process involving environmental, genetic, other factors and promoted by EBV
Hodgkin's lymphoma
accounts for 1/3rd of all lymphomas in the western world;
one of the 1st cancers cured by radiation
one of the 1st cured by combination chemotherapy
one of the most curable cancers
Hodgkin's Symptoms
painless, swollen lymph nodes in the neck, underarm or groin
night sweats
weight loss
itchy/sensitive skin
Diagnosis of Hodgkin's lymphoma
presence of Reed-Sternberg cells;
EBV can be found in Reed-Sternberg cells in 1/2 of all Hodgkin's lymphomas
Nasopharyngeal carcinoma
rare in US (2% of all head and neck cancers)
more frequently in SE Asia & N Africa
Men are most likely to develop NC than women
Nasopharyngeal carcinoma symptoms
lump in the neck
bloody discharge from nose
nasal congestion on one side of nose
hearing loss in one ear
frequen ear infections
double vision
face/neck pain
feeling of fullness in throat and sinus areas
Diagnosis of NC
screenings may look for EBV and/or exam w/endoscope
Oral Hairy Leukoplakia (OHL)
manifestation of EBV infection in an immunocompromised host;
primarily a result of virus multiplication and lysis in host cells;
responds well to antiviral therapy (systemic Acyclovir and Valacyclovir effective in ~90% of cases)
Mono vs OHL/BL
Mono = vigorous cell immunity waging war on EBV
OHL and Burkitt's lymphoma = lack of effective cell immunity
EBV pathogenesis
infects B cells & epithelial cells of the oropharynx which promotes shedding into saliva for transmission;
if infected cells permit transcription of the ZEBRA protein (Transcriptional activator protein), genes are transcribed and virus goes into lytic cycle; virions enter blood, cause viremia and infect additional B cells. Cytotoxic T cells attack and kill infected B cells causing the symptoms

Virus can evade host cell immunity by splicing its DNA into host cell
EBV lab diagnosis
blood work reveals hyperplasia
atypical lymphocytes (more basophilic and vacuolated cytoplasm than normal lymphocytes; nucleus may be oval, kidney-shaped or lobulated)
lymphocytosis (60-70% WBCs are mononuclear w/30% atypical lymphocytes)
heterophile antibody & antibody to viral antigens
Heterophile Ab
detected by end of 1st week of illness;
excellent indicator of EBV infection in adults, not kids
Paul Bunnell antigen (PB Ag)
found on sheep, horse and bovine RBC but NOT guinea pig kidney cells.
Used to test for IgM Ab produced by EBV activated B cells.
Sheep, horse, bovine but not guinea pig kidney cells = heterophile positive
If heterophile test is negative
IgM Ab to VCA, to EBNA etc
EBV Abs are used to diagnose mono if symptomatic with negative Mono test.
Recommended tests: Viral capsid antigen (VCA)-IgM, VCA-IgG and D early antigen (EA-D) tests to detect a current or recent infection.
VCA-IgG and Epstein Barr nuclear antigen (EBNA) tests detect previous infection
EBV complications
rupture of the enlarged spleen
hemolytic anemia
Guillain-Barre syndrome
Guillain-Barre syndrome
rare nervous system disorder resulting from nerve damage caused by the body's immune system in response to infection
EBV transmission
blood transfusions
organ transplants
Treatment of EBV
self-limiting and resolves on its own; treat symptoms
Cortisone for severly swollen tonsils or throat tissues which threaten to obstruct breathing
Penicillin/erythromycin for possible strep (not ampicillin or amoxicillin due to potential rash)
Plasma exchange or intravenous immune globulin (IVIG) for Guillain-Barre syndrome
EBV extra facts
1st virus found to contain micro RNAs (miRNAs; found in B cell latency)
CMV Family
CMV Subfamily
CMV Genus
CMV Species
Human herpesvirus 5 (Cytomegalovirus)
CMV structure
Capsid: icosahedral
Genome: dsDNA, linear
Enveloped: Yes
CMV info
largest genome of the human herpesviruses;
encodes largest # of glycoproteins among herpesviruses;
most prevalent viral cause of congenital infections;
issue particularly with AIDS patients and solid-organ transplant recipients
can cause birth defects if woman seroconverts during pregnancy
What does CMV cause?
Heterophile negative infectious mononucleosis
infections of multiple organs in AIDS patients
organ rejections
50% of adults in US have CMV;
most cases, shedding of virus is symptomatic
symptoms are milder version of mono
Histologic landmark for CMV infected cells
cytomegalic cell (enlarged cell that contains dense, central, "owl's eye" basophilic intranuclear inclusion body.
CMV diagnosis
cytomegalic cell
viral culture (takes 2 weeks to 1 month for cultivation)
serology: indirect ELISAs detect anti-CMV Abs
Direct detection of CMV antigens (early antigen p72 and late antigen p65) in blood, CSF or bronchioalveolar lavage through immunofluorescence
PCR, DNA hybridization assays
early p72 and late p65 antigens
detected in blood, CSF or bronchioalveolar lavage through immunofluorescence to detect active CMV infection
CMV complications
Primary infection usually self limited;
rare complications: pneumonitis, aseptic meningitis, Guillain-Barre syndrome
CMV transmission
saliva, urine, blood, throat washings, tears, breast milk, semen, stool, vaginal and cervical secretions, and transplant tissues

orally, sexually, blood transfusions, transplants, in utero, at burth and by nursing
Groups at risk of CMV infection
babies (prior to birth or within 1st month of life)
sexually active ppl
blood and organ recipients
burn victims
immunocompromised individuals

(responsible for the failure of many transplants)
Risks of contracting CMV
if seronegative and exposed to CMV;
worldwide and non-seasonal in occurrence;
seroprevalence from 30-100% depending on age, geographic location, and ethnic/socioeconomic background.
US seroprevalence is around 40-50%;
congenital CMV prevalence in US 0.5-1.5%
CMV Treatment
- Acyclovir (less potent than others)
- Ganciclovir
- Valganciclovir
- Cidofovir
- Foscarnet

Passive administration of CMV serum immunoglobulins is commonly used for prevention or treatment of CMV disease following organ transplantation