Herpesvirus 1, 2, 3
1&2 = HSV
#4 = EBV
Herpesvirus 5, 6, 7
5 = CMV
6 = HHV6
7 = HHV7
Herpesvirus genome and structure
-Envelope, tegument, and capsid
Herpesvirus produces proteins in what three phases
Immediate Early proteins (alpha) regulate gene transcription
Early proteins (Beta) DNA pol and TF's
Late Proteins (Gamma) = structural proteins
Herpesvirus envelope is from ______
Herpesvirus encodes what two enzymes
80% of Herpesvirus are ______
Oral herpes (acute gingivostomatitis) incubation time
Cold sores =
Herpes labialis prevalence?
Herpes Keratitis most frequent cause of ______
Major signs of herpes keratitis
- Unilateral red eye
- Vesicular skin rash
- Folicular conjunctivitis
DENDRITIC CORNEAL ULCER (= hallmark sign)
Herpes keratitis Tx
Acyclovir cream 3%
Herpes Whitlow caused by
HSV 1 or 2
Herpes whitlow incubation period
Herpes whitlow infection characteristics (3)
Treatmtent is SELF LIMITING
Herpes gladiatorum appearance and treatment
Head and neck blister cluster
Treatment is acyclovir
Eczema herpeticum epid, features, incubation, and Tx
- Rare, usually children
- Severe disseminated disease at pre-existing sites of skin damage
- Incubation of 5-12 days
- Tx = Acyclovir and ANTIBIOTICS to prevent 2' infection
Genital Herpes systemic effects
Fever, flu-like symptoms, swollen lymph nodes
Genital HSV2 lasts about _______
HSV encephalitis usually caused by
HSV accounts for __% of all encephalitic viral infections
HSV encephalitis phases
Prodrome = fever and nausea
Encephalopathy = either acute or subacute
HSV encephalitis has a predilection for edema and hemorrhage in ______
CSF appearance in HSV encephalitis
Glucose and protein = mostly normal
Elevated WBC (mostly lymphocytes)
RBC found becaue of hemorrhage
HSV meningitis mostly caused by ____
50% of HSV meningitis cases are _____ and 50% are _____
Primary and Secondary
HSV enceph vs. meningitis -- CSF appearance
Enceph has way higher RBC
Meningitis has higher WBC and Protein
Neonatal herpes caused mostly by
Neonatal HSV can be transmitted...
- vertically from mom
- from another neonate
Symptoms of neonatal HSV (after vs before birth infections)
After Birth = Many confined to skin, eye, and mouth. Encephalitis in 35%. Disseminated in 25%.
Before birth = Premature birth, low birthweight, microcephaly, hydrocephalus, chorioretinitis, vesicular skin lesions
- HSV replicates in ______ cells.
- Hangs out in the ______ and______ ganglia.
- Establishes ________
- trigeminal and sacral
HSV1 and 2 cause 3 types of infections:
Lytic (replication in mucoepithelial cells, disease @ lesion site)
Persistent (in lymphocytes and MQ
Cell death during HSV infection can result from _____, _____, or _______
- Virus induced inhibition of cell molecules
- DNA degradation
- Cytoskeleton disruption
Other cellular hallmarks of HSV infection
- COWDRY bodies (acidophilic intranuclear inclusion)
Innate ___________ may be sufficient to limit HSV infection
innate protection by interferon
Antivirals for HSV
- Anything ending in "cyclovir" (A, Pen, Val, Fam)
- Adenosine Arabinoside
Varicella is a result of _______ infection of VZV
Varicella Pox appearance
vesicle, pustule, crust, scabbed lesions
Lesions appear for 3-5 days
Varicella incubation period
about 2 weeks
When is chickenpox contagious?
2-3 days before rash appears
__________ can be observed during the course of chickenpox infection
ALL stages of lesions
Varicella rash characteristics and associated diseases?
- more prevalent on trunk
- SCALP presence distinguishes it from other rashes
- May cause Interstitial PNA in 20-30% of adults (from inflammatory rxn at site of lesion)
Herpes Zoster is a _______ infection of __________ Varicella
recurrent infection of latent VZV
Shingle rash is usually ________ and forms a __________
forms a "dermatomal pattern"
VZV transmission via ________, rarely _____
VZV initially infects the _________ and spreads to ________ by VIREMIA
Syncitia and intracellular inclusions occur in VZV because the virus...
is spread cell to cell
VZV is latent isn _________ or __________
DRG or Cranial nerve ganglia
Who is given VZV immunoglobulin? (3)
- IC patients
- Exposed staff
- neonates from infected mothers
VZV vaccine = _______
VZV vax can be effective when given...
(antibodies and CMI are stimulated)
VZV vaccination in adults is an effective means to...
boost antibodies to reduce onset of zoster
Epstein Barr Virus: Family/Herpesvirus type
EBV genomem, shape, and surface proteins
gp350/220 + gp110
EBV gp350 surface protein forms _________, and binds to _____ receptor on B cells
Glycoprotein complex I
CD21 (CR2) on B cells
EBV internalization occurs by ______
Three potential outcomes for EBV infection
Replicate in B cells or epithelial cells
latent infection of B cells
- Stimulate and immortalize B cells
EBV transcription and translation start with _________ genes
Two types of EBV cellular infections
- Permissive (Epithelial and B cell)
- Nonpermissive (B cell)
Viral capsid and glycoproteins that are synthesized by EBV (3) during a Permissive Epithial & B cell infection
- Early antigen (EA)
- Viral Capsid Antigen (VCA)
- Glycoproteins of the membrane antigen (MA)
EBV: Three viral genes that are expresed depending on the state of the B cell
**This is part of what type of B cell infection??**
EBNA's = E-B nuclear antigens
LMP's = Latent membrane proteins
LP's = Latent proteins
**Non-permissive B cell infection**
What are EBNA's and LP's?
DNA binding proteins
establish and maintain infection
What are LMP's?
Membrane proteins with oncogenic-like activity
(stimulate and immortalize B cell)
EBV establishes latency in _________
Memory B cells in which only the EBNA and LMP are expressed
Purpose of the DNA binding protiens and LMPs (overall)
maintaining the genome in the B cells but minimizing chance of immune recognition of the infected cells
Permissive epithelial and B cell infection results in ____________
Heterophile Antibody-Positive Infectious Mononucleosis (Mono)
Sx of infectious mononucleosis
exudative pharyngitis (w HIGH FEVER)
Serious complications with mono:
- Laryngeal obstruction or splenic rupture
Anti EA and Anti VCA antobidies occur within __________, while anti EBNA antibodies are formed at about __________
EBV incubation period is roughly _________
3 diseases from Non-Permissive B cell infection:
- EBV-induced Lymphoproliferative Disease
- Burkitt's Lymphoma
- Nasopharyngeal Carcinoma
EBV induced Lymphoproliferative disease characteristics (3)
(CBC, immune response, and who is most likely to get it)
High B cell lymphocytes
Lack of T cell response d/t immunosuppressive drugs
- occur at higher rates in heart and lung transplant patients than those getting bone marrow or kidney/liver
Burkitt's lymphoma definition =
Agressive monoclonal B cell lymphoma of the jaw and face
Affects children, associated with HIV (AIDS-associated malignancy)
NP carcinoma endemic in ______.
Proliferation of _______ cells.
- Asia + N. Africa
- Epithelial cells
- Nasal discharge, nosebleed, PT tube obstruction, Metastasis to other organs
EBV transmitted by (3)
saliva, oral contact, fomites
Clinically, EBV causes _____ or ______ infections
Acute or latent
Acute EBV infection pathogenesis (three steps)
replication in NP cells
spread to Salivary gland
VIREMIA and infection of RE system
EBV latent infection:
1. Virus is present as _____ in B cell and epithelial cells.
2. Viral ______ rate is low
3. What cellular interaction causes this to occur?
reactivation rate is low
- happens from NP cells infecting passing B cells
B cell proliferation in EBV infection causes increase in __________
T cell activation during EBV infection results in __________
atypical lymphocytes called DOWNEY CELLS
What is a Downey Cell?
large lymphocye due to antigen stimulation
Have basophilic cytoplasmic rim
Heterophile antibody results from activation of _________
When can it be detected/how long does it last?
detected at 1st week, can last several months
Heterophile is a great indication for whom?
Adults (not reliable in children)
What is a Paul and Bunnel test?
detects Antibodies that cause agglutination of RBC's from another species (horse)
___% of adults have been infected with EBV by age 40
Infants are susceptible to EBV when?
When mom's antibody protection wears off
EBV diagnostic tests (4)
- Physical exam (look at SPLEEN)
- MonoSpot test
- Microscopy for Downey Cells
Explain the blood test to determine the stage of EBV infection.
- No VCA antibodies = susceptible
- IgM to VBA but no EBNA = Primary infection
- VCA and EBNA antibodies = Past infection
- Elevation of antibodies to EA in presence of EBNA antibodies = REACTIVATION
CMV family member (and class)
Three infections from CMV
- Congenital CMV
- Heterophile-negative mononucleosis
- Diseases of Immunocompromised patients
Congenital CMV: _____ infection from mom is spread to placenta.
_______ infection in mom rarely causes congenital abnormalities
CMV may cause ________ or ________ symptoms
Give some examples of both.
Temporary (liver, spleen, lung, seizure)
Permanent (Hearing/vision loss, Microcephaly, Mental disability)
Heterophile-negative mono is similar to IM except for...
Paul-Bunnell test is negative
CMV diseases in immunocompromised patients include
CMV cellular hallmark
What are Cowdry bodies?
giant multinucleated cells in CMV infection
found in Parotid gland
OWLS EYE appearance
CMV causes ______ infection in salivary, breasts, kidneys, and peripheral blood leukocutes.
This leads to _____________
Leads to chronic excretion by the organ involved.
CMV incubation period
CMV main sites of replication
Salivary glands and Kidneys
drugs possess many sides
Drugs = Ganciclovir, valganciclovir,
HHV6 and HHV7, also known as...
HHV6 infects what cells? Where does it replicate
lymphocytes, monocytes, epithelial and endothelial cells
Replicates in salivary glands
****These are both similar to CMV****
Roseola (6th disease) due to ____ more than ______
HHV6 more than HHV7
Roseola is a common _____________ disease affecting _____
When/where does Roseola rash appear?
After three days (after fever)
appears on neck, trunk, thighs
_____ infections of Roseola (HHV6) can cause other complications, such as...
What about IC patients?
Primary infections can cause encephalitis, lymphadenopathy, and hepatitis
**May cause these things in Immunocompromised patients upon reactivation.
Another name for infantile Roseola
Infection with HHV6 and 7 occur mainly during ________
Seroprevalence of HHV6 in 2 year olds approaches...
HHV7 antibody prevalence in adults reaches ____%
What is HHV8
Kaposi's Sarcoma-associated Herpes
HHV8 causes ____ or _______ infections
It infects ____________ cells but multiplies in ________ cells
latent or lytic
Infects peripheral blood lymphocytes but multiplies in endo/epithelial cells and monocytes
Kaposi's sarcoma is a ___ tumor form ______ lineage
spindle cell tumor derived from endothelial cell lineage
Kaposi Sarcoma locations
under skin, in oral lining, nose, and throat
Kaposi sarcoma can be limited to _____ or may...
mucocutaneous lesions or may spread to other otgans
Kaposi sarcoma cancer spreads to ___ or ____ causing bleeding and function issues
GI or lungs
HHV8 is a defining illness for what?
HHV8 may be spread via what routes?
Sexual or Nonsexual
nonsexual = poorly understood
HHV8 treatments (2)