What are the eight impurtant human pathogens in herpeviridae
HSV-1 HSV-2 VZV *alpha-short replicative cycle, broad host range HSV-6 HSV-7 CMV *beta- long replicative cycle, restricted host range HSV-8 (Kaposi's sarcoma-associated HV) EBV *gamma- very restricted host range
Well-known manifestation of herpes virus
Vesicular and pustules formation on skin
Mode of infx of herpesvirus
Latent or lytic
Long genome of herpes virus encodes for enzymes for
Metabolism of nucleic acid
DNA synthesis
Processing proteins
The viral genome synthesis and capsid assembly occurs in
Nucleus
Productive viral infection means
Inevitable cell destruction
Four layers of the herpesvirus
Envelope (glycoproteins and altered host membrane)
Tegument (protein coat with viral enzymes)
Icosahedral capsid (160 capsomeres)
DNA core (double stranded)
Its envelope protein encodes for 11 glycoproteins
Human simplex virus
Binds with glycosaminoglycans
gB
Interacts with GAG heparan sulfate of the target cell
gC
Responsible for stability during entry fusion (HVEM host cell receptor) and elicits production of neutralizing antibodies
gD
Interacts with the Fc receptor of IgG
gE
Type-specific and allows antigenic discrimination between HSV-1 (gG-1) and HSV-2 (gG-2)
gG
Complexes with gE and interacts with the cell junction to spread the virus from cell to cell
gI
For virus capsid development (encoded by HSV)
gK
Important for the viral cell entry
gH-gL complex
Interaction with cell junctions to facilitate cell-cell spread (same function with gI)
gM
What accounts for the low immunity to HSV?
Virus defense mech: Virus attaches to fc receptor of IgG to neutralize antibods
The virus is transmitted through close contact bcos
It is found in semen, saliva, fluid in female genital tract, fluid in lesions
T or F: hsv can be harbored in monkeys
False??- no known animal vectors
Host cell receptors for HSV entry
Heparan sulfate (HSV1 only) -GAG Herpes virus entry mediator (HSV 1 and 2) -member of TNF Nectin 1 (HSV 1 and 2) Nectin 2(HSV 2 only) -members of Ig family
HSV exit
Budding via cytloytic mech.
Phases of replication of HSV
Immediate early- viral protein steps
Early- transcription of alpha genes via DNA dependent RNA polymerase II (product- posthoc phospoprotein)
Middle- transcription of beta genes (prod- DNA dependent DNA polymerase)
Late- gamma genes (most r structural proteins)
Where does HSV usually exist in a nucleus during latency
Episome
Target of HSV, presents virus to b and t cells
Langerhans cells
Both cmi and HMI are triggered by hsv
Trohth
Phase of latent infection of hsv going to sensory neuron to stay for years (establishment)
Retrograde transport
Phase of latent infection of hsv moving out to peripheral nerve to form viruses and infect healthy cells (reactivation)
Anterograde transport
HSV-1: _______::HSV-2: ________ ganglia
Trigeminal, lumbosacral
Tyoe of HSV more associated with orofacial lesions, fever and blisters, encephalitis
HSV-1
Type of HSV which is sexually transmitted, causes genital lesions and meningitis
HSV-2
Distinguishing feature of HSV
blisters in genital area, rectum, mouth
Why must hsv isolation be carried out immediately
Virus is labile
Smear used for presumptive id of HSV using cell scrapings of the lesions
Tzanck smear
Found in tzanck smear of cell scrapings/lesions
Multinucleated giant cells/syncytia
Ballooning cytoplasm
Cowdry type A intranuclear inclusion
Big nuclear body surrounded by a white halo
Innate immune receptors sre stimulated by ________ to induce prod of type 1 IFN
TLR (2: viral glycoprotein and 9: Viral DNA)
Group where varicella zoster virus is in
Human Alpha herpesviruses
VZV transmission
Direct contact and airborne
When is the VZV infected person contagious?
1-2 days before rash onset
AEROSOL SIZE OF VZV
0.5-30 micrometers diameter
Target of VZV
upper respiratory mucosa and conjunctiva
Primary viremia of VZV happens in
Liver and spleen
Secondary viremia happens in
Infected mononuclear cells
Where does primary replication of vzv happen
Regional lymph nodes and lymphoreticular tissues
Common complication of VZV
Postherpetic neuralgia/ZAP
Most common site of original varicella lesions
Thoracic dermatome
Varicella vesicles exhibit
Centripetal distribution. Lesions form crop become pustules, break down and scab over
T or F: VZV is more severe in children
False
Flared up varicella in vaccinated
Breakthrough varicella
T or F: rashes in varicella in vaccinated is more vesicular than maculopapular
False, maculopapular than vesicular
Common symptoms of herpes zoster/shingles
Headache, photophobia, malaise, fever, abnormal skin sensations and pain
Describe herpes zoster rash
Unilateral, involves 1-3 dermatomes, rash is erythematous then maculopapular.
**zoster sine herpetes- no rash forms
Specimens used for diagnosis of VZV
Swabs from vesicles
Skin lesion scrapings
Vesicle fluid
What does a positive IgM ELISA mean for VZV?
primary VZV infection, re-infection, or re-activation
Why is it difficult to detect increase in IgG for HZ?
patients may have a high baseline antibody titer from prior varicella disease
*IgG detects previous VZV infection
What is a disadvantage of electron microscopy as diagnosis?
Cannit differentiate fromother herpes virus
Purpose of laboratory diagnosis for vzv
- confirm clinical diagnosis
- determine susceptibility
- determine if wild type or vaccine strain
T or F: HMI is primarily involved in vzv immunity
False, CMI and interferon
Varicella vaccines
Varivax*
Proquad*
-MMRV
Post exposure Prophylaxis
-use in healthy persons wo evidence of immunity within 3-5 days after exposure to varicella
-VARIZIG (certain groups at high risk for severe disease after exposure to VZV and within 10 days of exposure)
**LAV
Herpes zoster vaccines
Live attenuated vzv- subcutaneous admin. 14x more potent
Zostavax
**no for >60 yo with varicella vax and immunocompromised
High titer of antibody to virus, orevents varicella in immunocompromsied and infants
Varicella zoster immune globulin
Major target of EBV and main reservoir of latency
B lymphocytes
Infected by EBV
Oral epithelial cells
Epstein barr virus primarily causes this
Acute Infectious mononucleosis
It binds to MHC II on B cell membrane surface
Gp42
Binds to cd21/cr2
Gp350
Entry of EBV
Endocytosis
Ampicillin rash is senn in this stage of infection of EBV
Primary stage
Triad of symptoms of EBV
Fatigue, swollen lymph nodes, pharyngitis
Kissing disease which is marked by extreme fatigue, fever, sore throat, head and body aches, swollen lymph nodes in the neck and armpits, swollen liver or spleen or both, rash
Infectious mononucleosis (polyclonal stimulation of lymphocytes)
Four determinants of EBV in blood test
Viral capsid antigen (VCA-IgM): first to appear
VCA-IgG: second to appear, remains during convalescence
D early antigen (EA-D)
Epstein Barr nuclear antigen (EBNA)
Seen in bloow work up of EBV infected patient
Increasd wbc, abnormal liver, low neutrophils and platelets
indiccator of active infection
VCA-IgM
Positive EAD
indicates past and current infection
Indicative of any EBV infection
VCA-IgG
EBNA is only positive for
Reactivation of virus and past infection
Other complications of EBV
Lymphoproliferation
B cell hyperplasia
Nasopharyngeal carcinoma
Burkitt lymphoma (viral DNA is incorporated)
Double stranded DNA
largest genome in herpes group
Has cytoplasmic inclusion bodies and induction of giant cells
Cytomegalovirus
Hearing loss, vision loss, hepatitis, mononucleosis
Cytomegalovirus
3 clinical syndromes of CMV
- congenital CMV
- mononucleosis
- immunocompromised host
Lab diag of CMV
Blood test
**babies:2-3 wks after infx
Exanthem subitem (roseola) and rejection of transplanted kidneys
HSV 6 and 7
Kaposis sarcoma in AIDS patients and intraabdominal tumors
HSV8
Encephalitis, brain damage in survivors, bites of rhesus monkeys
B virus
Taxonomy of herpes viruses
Lymphocryptovirus: EBV Varicellovirus: VZV Simplex virus: HSV1 and 2 Rhadinovirus: HSV8 Roseolovirus: HSV 6 and 7