What type of nucleic acids do we have in Herpes viruses
Double stranded DNA
How can we distinguish the herpes viruses under microscopy?
What are herpes viruses susceptible to generally?
Susceptible to drying, inactivation by heat, mild detergent and solvents because of their membrane envelope
Where do herpesviruses replicate?
Types of Herpes Viruses?
Alpha Beta Gamma
What viral types fall into the Alpha category?
HSV-1 HSV-2 VZV
Presentation of HSV-1
Labial lesions (cold sores), fever blister, keratitis, encephalitis
Presentation of HSV-2
Genital lesions, severe CNS disease in neonates (congenital herpes infection)
Presentation of VZV
Herpes Zoster - Chicken pox, shingles - Transmitted by respiratory droplets
Where do alpha herpes viruses stay latent?
What viral types fall into the Beta category?
CMV HHV-6 HHV-7
Which category, Alpha or Beta, has the longest replicative phase?
Beta Alpha's is short
Where do Beta viruses stay latent?
Monocytes/macrophages Lymphocytes Endothelial cells
Monospot test result for CMV?
Histological finding for CMV?
HHV-6 is associated with what symptoms? How is it transmitted?
Roseola Transmitted by saliva
High fevers for several days that can cause seizures followed by diffuse macular rash.
What viral types fall into the Gamma category?
EBV (HHV-4), KSHV (HHV-8)
Karposi's sarcomma-associated herpesvirus: these viruses cause Karposi's sarcoma, a cancer common in AIDs patients
Epstein-Barr virus: cause of infectious mononucleosis (glandular fever). Infants are susceptible to EBV after their maternal antibody protection dissapears
What cells are infected by Gamma category viruses?
Epithelial cells and lymphocytes
What cells do gamma category viruses stay latent in?
Lympocytes and endothelial cells
Flu-like symptoms caused by HHV-4 (EBV)
Fever, hepatosplenomegaly, pharyngitis
Besides EBV, what virus type causes mononucleosis?
What cells does EBV target specifically?
EBV monospot test result?
HHV-8 is associated with what?
A Kaposi sarcoma, a neoplasm of endothelial cells. Seen in HIV/AIDS patients and transplant patients. Dark, violaceous, flat but nodular skin lesions
How is HHV-8 transmitted?
Life Cycle of Herpes
1. Lytic Replication 2. Latency 3. Reactivation
Lytic Phase, generally:
In epithelial cells, viruses take over cellular machineries for replication, synthesis of macromolecules and virus assembly, and eventually leads to cell death
Proteins made by viruses do what, generally:
Proteins are produced that prevent premature programmed cell death or apoptosis and evade immune responses
What DNA replication enzymes can herpes viruses make?
All herpesviruses encode enzymes used in DNA replication: 1. ribonucleotide reductase 2. thymidine kinase 3. primase/helicase 4. DNA polymerase
What are the immediate early genes?
Transcriptional regulatory factors that turn on delayed early gene expression
What are the delayed early genes?
DNA replication enzymes
What occurs during the DNA replication phase?
DNA replicates as covalently closed circle, followed by the rolling circle mechanism
What are the late genes?
General description of the Assembly/egress phase for viruses
Capsid generated around created proteins, primary envelopment (nuclear membrane envelops it), leave nuclear membrane, enveloped by golgi (secondary envelopment), exits
What is occurring during the latency phase?
Circular viral genome (episome) maintained in neurons without replication; expresses LAT transcript, which plays a role in latency establishment and evades immune detection
Reactivation of HSV-2 - Triggers
Stress, sunlight, trauma, menstruation
Triggers for VZV reactivation
Immune suppression, depressed cell-mediated immunity (age)
Reactivation process for HSV-2
Involved limited viral replication in neurons, transport of viral capsid to axonal terminals and egress to regions innervated by specific neurons. Asymptomatic reactivation facilitates virus spread to naive hosts.
Clinical features of HSV primary infection?
Accompanied by systemic symptoms such as fever and malaise
Clinical features of HSV reactivation
Accompanied by prodromal symptoms like pain, numbness, itchiness, tingling sensation
Clinical features of HSV acute infection
Direct destruction of tissues or induction of immunopathologic response 1. Characteristic skin lesions are vesicles with an erythematous base 2. Usually grouped at a single anatomic site
HSV Type, Age, and outcome for: Ocular Herpes
1 All ages Resolution with occasional visual impairment
HSV Type, Age, and outcome for: Oral herpes
Usually 1 All ages Just resolves
HSV Type, Age, and outcome for: Genital herpes
Usually 2 Adolescents and adults Just resolves
HSV Type, Age, and outcome for: Neonatal herpes
Usually 2 Age: 0-4 weeks Leads to development impairment
HSV Type, Age, and outcome for: Meningoencephalitis
2 Adolescents, adults Just resolves
HSV Type, Age, and outcome for: Encephalitis
1 All ages Leads to severe neurological impairment and death
HSV Type, Age, and outcome for: Disseminated herpes
Usually 1 All ages Can resolve or kill you
How to diagnose Herpes infections
1. viral culture 2. Tzanck smear (Smear of an opened skin vesicle to detect mononucleated giant cells) 3. serology 4. PCR
How does Herpes Thymidine Kinase Anti-Herpes Therapy work?
DNA chain terminator, specifically activated by the viral TK. Incorporates into the viral DNA and terminates the DNA replication of viruses
A TK antiherpes that inhibits viral DNA polymerase and chain terminates
CMV does not have a viral TK but can be inhibited by ganciclovir. A viral protein kinase homologue is involved in activating ganciclovir
Treatment for CMV?
Used in the treatment of CMV retinitis in AIDS patients receiving AZT therapy. Has renal side effects and must be administered by IV continuously
How does Foscarnet work?
Binds directly to the pyrophosphate-binding sites of RNA or DNA polymerases. Does not need to be activated by cellular or viral kinases
Live-Attenuated VZV vaccine
Who is Varivax recommended for?
- Kids - Non pregnant women of child bearing age - Those with humoral immunodeficiencies - HIV+ children with age specific CD4+counts greater than or equal to 25%
Varivax not recommended for?
- Pregnant women - HIV+ persons or persons with other cellular immunodeficiencies - People receiving immunosuppressive therapy, steroids, etc.
Which is more severe? Primary infection or Recurrent?
Primary - No immunity yet