Lecture 83_84: Herpesvirus' CMV, EBV, VZV, HHV 6, HHV 8 Flashcards
Describe the basic structure of All herpes viruses
proteins for attachment?
Proteins for fusion?
Enveloped
Icosohedral capsin
Double Stranded DNA – Linear
Tegument
attachment – gB and gM
Fusion – gH
There is no cure for herpes viral infection
Common cause of illness in immuno compromised patients
CMV -- Whats the HHV #? whats in the tegument? The genome -- IE, E, L genes? what other unique features?
HHV - 5
Tegument – contains pp65 and mRNAs
The Genome – 700 proteins – largest of the herpes viruses
IE genes – function in viral DNA synthesis (regulators)
Early genes – Function in DNA replication and Viral protein modification –
Late Genes – structural gene products
miRNAs – shut down the cell machinery
CMV – modes of transmission
HEENT -- shedding in oropharynx, tears, saliva GU - urine, sexual transmission Blood transfusions Breast milk Solid organ and BMT Congenital
CMV – describe a few disease manifestations?
What % are asymptomatic ?
80-90% Asymptomatic
Mononucleosis – Heterophile antibody Negative
Retinitis – Esp in AIDS patients – (white patches of infarct leading to “ketchup on scrambled egg” appearance)
Pneumonia –
Glomerulopathy
Hepatitis, Gastroenteritis
Periventriculitis – ventricles light up on CT
Transverse Myelitis – inflammation of the spinal cord – some paralysis or peripheral nerve involvement
Hearing Loss - 8th nerve involvement
Cytomegalic Inclusion Disease – vertical transmission at birth; Leading infectious cause of birth defects in the US; the early a mom infected during pregnancy, the worse
Mental Retardation
ITP
Immunosenecence
What are the different tissues types that can be infected during:
Permissive infection
latent Infection
Persistent infection
permissive – epithelial cells (mouth to anus)
Kidneys, lungs, colon
Latent – Hemopoeitic cells –
anemia, neutropenia, TTP
Persistent Infection – lymphocytes, endothelial cells, bone marrow
What is the Pathognomonic histological finding for CMV Infection?
“owl’s eye” inclusions
Immune Responses to CMV
Antiviral Antibodies:
1) Virolytic – attract complement for lysis of the virus
2) Non virolytic – complement independent
Cell mediated Immunity
- CD8, NK, — keep CMV from reactivating in the host
What are the criteria for diagnosis of CMV?
Evidence of viral replication + Systemic signs of disease
Evidence of viral replication = PCR, Histopath, IHC of antibodies or antigens; Shell vial method
Systemic Signs of Disease: Fever, Luekopenia, TTP, elevated transaminases
Prevention of CMV
Screening of solid organ and blood transfusion
Barrier protection for sexual intercourse
Antiviral Prophylaxis – Ganciclovir, Valganciclovir, Acyclovir
Bolster T cell mediated Immunity
Inactivated vaccine (Towne)
Treatment of CMV
Ganciclovir
Foscarnet – watch for renal toxicity
Hyperimmune Globulin – in combo with Gan or Fos
Valganciclovir – for retinitis
some resistance is developing
Epstein Bar Virus
- HHV #?
- Tropism
-
HHV - 4
Tropism – Complement Receptor 2 (CR2) – which is only on B lymphocytes and Oral/Nasopharyngeal epithelium (kissing disease)
Can also infect Cervical epithelium
EBV –
What % are symptomatic ?
Describe some clinical manifestations of disease
90% asymptomatic
Mononucleosis – Heterophile antibody positive
fever, pharyngitis, LAD
Rash when given Ampicillin
ITP, anemia, rash with ampicillin
Pneumonitis
Transverse melitis/peripheral neuropathies
immuno-senesence
Post Transplant Lymphoproliferative disease
What are some malignancies caused by EBV?
Burkitt’s Lymphoma
Hodgkins Lymphoma
Nasopharyngeal carcinoma
EBV manifestatins in the Immuno compromised
Hairy oral luekoplakia
Post Transplant Lymphoproliferative Disorder – may develop into lymphoma
Diagnosis of EBV
Evidence of Viral Infection + Replication
Evidence of Replication;
Quantitative PCR – evidence of EBV DNA
Positive Immunocytochemisitry — proteins/nucleic acid associated with EBV (LMP, EBER Stains)
+ systemic signs of disease: Fever, pharyngitis, LAD
Prevention of EBV
Don’t share food, drinking glasses, utensils
Barrier protection
Don’t donate blood 6 months afte rmono
Vaccines in trial
EBV PTLD – acyclovir, ganciclovir prophylaxis
bolster cell mediated Immunity
Treatment of: Mono Pneumonitis Hairy leukoplakia Burkitts Lymphoma/Naso-oro pharyngeal carcinoma PTLD
Mono – supportive care; corticosteroids for severe disease
Pneunmonitis/hairy luekoplakia – Aciclovir
Cancer – Chemotherapy
PTLD – Rituximab
Differentiation of causative agents of mononucleosis
CMV and HHV6 – Heterophile antibody negative (Monospot negative)
EVC – Heterophile antibody positive (Monospot positive)
Uses of Aciclovir
HSV 1 and 2: most sensitive
VZV: can use acyclovir, but need at higher doses bc there is some intrinsic decreased sensitivity EBV -- sensitive to acyclovir All over HHV -- inherently resistant to Acyclovir
Varicella Zoster Virus (VZV)
aka HHV #?
primary infection ?
Reactivation of latent infection ?
HHV 3
Primary infection – Chicken pox
Latent infection reactivation - Shingles
Clinical time course of the primary VZV infection?
transmission – respiratory secretions
Primary viremia – asymptomatic
9-13 days after infection – Secondary viremia; fever
10-20 days after infection – chicken pox (vesiculopustular rash); disseminated dew drop lesions
Stages of VZV infection
primary infection – chicken pox
Latent Infection -
90% in DRG or Cranial Nerve ganglia – paresthesias
10% in anterior horn cells – paralysis
Reactivated infecitons – Shingles; can be lifethreatening inthe immuno compromised
Complications of Primary VZV infection
who is the most susceptible to complications in general ?
describe some of the complications of primary infections
Susceptible: Immunocompetent Adults who get primary infections – 15-30x more likely
Immunocompromised persons – 1000x more likely
Complications: CNS- - meningitis, cerebellar ataxia Pnuemonitis Hepatitis Reye's Syndrome -- encephalopathy, hepatits, hyperglycemia associated with chickenpox + ASA
Disseminated disease - hemorrhagic chicken pox
Shingles –
manifestations and symptoms
Manifestations: Vesiculopustular Rash involving 1-2 contiguous dermatomes; disappears in 10 days
Prodromal Paresthesia or Pain
Associated with Allodynia – uncomfortable sensation to light touch or temperature
Post herpetic Nueralgias –
Shingles of the head and neck
Complications of Shingles
Complications in the immuno compromised
H&N shingles
- Herpes Zoster Ophthalmicus – reactivation of VZV within the first branch of CN V) – most concerning for encehalitis
-Poster Herpetic Angiitis – replication of virus in blood vessels of the brain; can lead to stroke like symptoms;
Complications of Shingles: Poster herpetic Neuralgias Encephalalitis with CN V Involvement Ramsey Hunt Syndrome Transverse Myelitis Guillan Barre
Immunocompromised –
Disseminated Disease of the skin
Visceral disease – pneumonitis, Hepatitis, Meningoencephalitis
Ramsey Hunt Syndrome
Poster Herpetic Angiitis
Reactvation of the geniculate ganglion
Symptoms:
Vesicles only present in the External Auditory canal
Ipsilateral Decreased of taste on ant 2/3 of tongue
Ipsilateral facial paralysis
Stroke like condition, complication of Shingles
- treat with both anti viral and anti-clotting
Dx of VZV
For chicken pox and shingles – usually a clinical dx
but if in doubt: pap smear, DFA, PCR (for CNS manifestations)
Prevention of VZV
patients are infectious before the rash state
avoid inhaling infectious drops
Avoid contact with skin lesions
Oka Vaccine
VZ Immunoglobulin – passive immune therapy use to prevent infection in newborns who had just contracted chichen pox;
Treatment of VZV
Chicken pox:
immunocompetent : Aciclovir; can help shorten duration, but usually not given
Immunocompormised – Aciclovir IV
Shingles:
Immunocompetent: Aciclovir, famciclovir, valciclovir
Must treat Ophthalamic zoster
Immunocompromised: aciclovir IV
HHV 6
general facts:
Beta Herpes Virus (like CMV – HHV 5)
Infection occurs earlier than EBV or CMV (usually by the age of 2)
95% infected by adulthood
For those infected; the disease becomes latent following primary infection; can insert but no evidence of malignancy
HHV 6 Disease Manifestations
Children
Adults and Children
what is DRESS ?
Children :
Exanthem Subitum – roseola
Diffuse maculo-papuilar rash on trunk
Fever; malaise; resolves on own
Children and Adults:
Mononucleosis – Heterophile Antibody Negative
CNS complications in Immuno Compormised:
Bone marrow Suppression
DRESS – “Drug Reaction and Eosinophilia with Systemic Symptoms” —
No maligancies
Diagnosis of HHV 6
Characteristic rash – self limiitng
SErology – igM and IgG
PCR – use for CNS dx
Treatment of HHV 6
Resistant to Aciclovir
Use: Ganciclovir, Foscarnet, Cidofovir
HHV 8 –
aka?
What herpes group is it in?
tropisms
what other features does this virus have?
what is LANA ?
aka – Kaposi’s Sarcoma Virus
gamma Herpesvirus –
Lymphotrophic and Angiotrophic
Urogenitial and GI Epithelial cells
Contains tumor promoters and oncogenes
11 proteins homooglous to cell proteins which may hlep it evade the immune system
Latent DNA is Episomal
but can insert and lead to malignancies
Expresses latency associated nuclear antigen
Epidemiology of HHV 8
What groups are have the highest prevelence?
how is it transmitted?
- Rare in the US but much higher is the HIV and MSM populations
93% prevelance in mediterranean countries and Africa
Sexually transmitted
Clinical manifestations of HHV 8
Rare:
Kaposi’s Sarcoma – Cutaneous and Visceral
Primary effusion Lymphoma –
Metacentraic Castleman’s disease
Rare: Pneumonia
Diagnosis of HHV 8
Serology - IgM, IgG
PCR of Tissue bx
LANA
Treatment of HHV 8
Resistant to Aciclovir
Use ganciclovir, valaciclovir, foscarnet, cidofovir
Sarco
