Herpes Viruses Flashcards
What are the three subclasses of herpes virus and which viruses are in each?
Alpha:
HSV1
HSV2
VZV
Beta:
CMV
HHV6&7
Gamma:
EBV
KSHV (HHV8)
What are the latency reservoirs for the alpha herpes viruses?
HSV1 - Trigeminal Ganglion
HSV2 - Sacral Sensor Ganglion
VZV - Dorsal Root Ganglion
What are the characteristic diseases for the alpha herpes viruses?
HSV1 - Oral lesions
HSV2 - Genital lesions
VZV - Chickenpox (primary), Zoster (Reactivation)
What are the latency reservoirs for the beta herpes viruses?
CMV - CD34+ myeloid cells
HHV6&7 - B cells/myeloid progenitor cells/T cells
What are the characteristic diseases for the beta herpes viruses?
CMV - Primary: mild disease or Mononucleosis-like syndrome. Immune Compromised: systemic disease with end organ damage
HHV6&7 - Infant: Roseola. Immune Compromised: End organ damage like encephalitis, pneumonitis
What are the latency reservoirs for the gamma herpes viruses?
EBV - B cells
KSHV (HHV8) - B cells
What are the characteristic diseases for the gamma herpes viruses?
EBV - Mononucleosis, EBV associated malignancies
KSHV(HHV8) - Karposi’s sarcoma, B-cell Lymphomas
How stable are herpes viruses, and how do they spread?
Labile and easy to decontaminate or kill in the environment = spread requires close contact.
What is the genetic and protein structure of herpes viruses?
Linear DsDNA
Spherical, enveloped visions
DNA surrounded by tegument (viral proteins with some RNAs and cellular proteins used to reprogram newly infected host cell.)
In the host cell, the genome is delivered to the NUCLEUS and forms an episome (circle).
Where does the herpes virus gain its envelope from, and what properties does the envelope provide?
Envelope derived from host Golgi, coated with 10-12 surface glycoproteins important for:
cell binding,
cell-cell spread,
and immune evasion.
What are the three stages of viral gene expression during lytic replication?
1st immediate early (IE) genes-set up environment conducive for viral replication and needed for expression of E and L genes. 2nd Early (E) genes-encode replication enzymes and nonstructural viral proteins. 3rd Late (L) genes- encode viral structural proteins needed for packaging a new virion and egress from infected cell.
Where in the cell does herpes DNA replication occur, what proteins are involved, and what diagnostic feature does this produce?
Herpesvirus DNA replication occurs in the nucleus using viral-encoded DNA polymerase and accessory viral proteins. Encapsidation of genome occurs in the nucleus. Thus, intranuclear inclusions (accumulated viral capsid proteins) are often diagnostic on histopathology for herpesvirus infection.
What are differences between primary and reactivation herpes infections common to all herpes viruses?
Most primary infections have a clinical presentation different than the disease associated with reactivation.
Primary infection results in LATENT infection in specific cells in the host.
Reactivation can be subclinical (shedding) or cause clinical disease. Both may result in spread of infection to new hosts.
Disease from reactivation is usually less severe than disease from initial infection.
Herpesvirus infection is more severe in patients with Tcell defects.
Describe latency in all herpesviruses
Small subset of viral genes expressed but no infectious particles produced
What is the purpose of viral glycoproteins?
- mediate cellular tropism (determines which cells the virus enters)
- Targets of the adaptive immune response
What do we use Acyclovir for?
Alpha herpesvirus
What do we use gancyclovir for mainly?
Beta herpesviruses
How does Acyclovir work?
chain terminator
Must have a thymidine kinase (betas dont)
Inclusion bodies
Indicative of Herpesviral infection
Intranuclear:
HSV, VZV: Cowdry type A
CMV: owl eyes
Intranuclear and intracytoplasmic :
HHV6, CMV
Host immune response to herpesvirus
Innate immune response: INF/cytokine production and NK cell activities
Adaptive immune response: neutralizing Ab, CD4+ and CD8+ t-cell functions
How does herpesvirus evade the innate immune response?
Block induction of type I interferons and other cytokines
Block dendritic cell maturation
Prevent complement activation
alter NK cell functions
How does herpesvirus evade the adaptive immune response?
Cytokine and chemokine mimetics and decoy receptors
Fc receptor binding proteins
Interfere with antigen presenting to t cells
What are two important complications of HSV1 int he normal host?
Herpetic keratitis
HSV encephalitis
Complications of genital herpes
Urethritis
Meningitis
Yeast superinfection
Perianal/perirectal disease
HSV in the immunocompromised host
Severe local disease (oral or genital)
Neonatal (severe/fatal)
Important role for antiviral
What’s the diagnostic test of choice for HSV?
PCR
How is VZV transmitted and what disease does it cause?
Through the air: respiratory secretions
Goes to lymph node, blood, liver, spleen, skin
Chickenpox
What population do we really worry about CMV with and give prophylaxis to?
transplant pts
Diagnostic tests for CMV
IgM
PCR
Tissue histology
Severe CMV in an immunocompromised host
Severe end organ disease + viremia
How do we treat disseminated CMV?
gancyclovir
If resistant- foscarnet
Congenital CMV infection (in utero)
90% are mild
10% severe: jaundice, microcephaly, enlarged liver/spleen, decreased platelets; moratlity (10-20%)
Roseola
HHV6 and HHV7
Beta herpesviruses
High fever for 3-7 days
Rash appears as fever end abruptly
Rash starts on trunk and goes to face, neck, extremities
Complications: febrile seizures, end organ disease in immune compromised
Treat immunocompromised with gancyclovir
EBV
Ebstein Barr Virus
gamma-herpesvirus
EBNA1 and EBNA2
NA1: links viral genome to cellular chromosome
NA2: turns on other viral latent genes and cellular-activation associated genes including c-myc
Mononucleosis
EBV Fever Adenopathy Pharyngitis Hepatosplenomegaly Atypical lymphocytes Heterophil antibodies (tested in monospot test)
Anti-EBNA
Negative during acute infection
Positive during latency
KSHV
HHV8 Causes kaposi's sarcoma Gamma-herpesvirus HIV Spread sexually
