Herpes Virus Flashcards
Describe the nucleic acid, capsid, and envelope of the herpes virus.
NA - double stranded DNA
Icosahedral capsid
Envelope with glycoprotein spikes on surface
How does herpes virus enter the cell?
Virus particle attaches to receptor on permissive cell believed to be heparan sulfate
The envelope fuses with the cell and the capsid moves to the nucleus, where the genome is released
What occurs to the viral DNA inside the nucleus?
Circularizes - results from terminal and internal nucleotide sequence redundancies
How are concatemers formed in herpes virus?
Rolling circle mechanism
What classes of mRNAs appear in herpes virus transcription and in what order?
alpha - immediate early
beta - early
gamma - late
*This creates a temporal cascade of mRNAs and the corresponding proteins
What kind of proteins are made from alpha mRNAs?
Regulatory proteins
What kind of proteins are made from beta mRNAs?
Enzymatic and required for DNA replication
E.g. DNA dependent-DNA polymerase and thymidine kinase
What kind of proteins are made from gamma mRNAs?
Structural proteins that are used to form progeny virus
Synthesized after viral DNA synthesis (aka late protein)
How are viral particles assembled?
Nucleocapsid formation occurs in the nucleus
Capsid passes through nuclear membrane site and acquires envelope from modified membranes of cytoplasmic vesicles having inserted viral proteins
What occurs to the host cell during viral replication?
Disruption of chromosomes by margination of cell DNA along nuclear membrane
Shut down of cell synthetic events
Cell death
What are the two serological types of herpes simplex virus and what kind of diseases do they cause?
HSV-1: oral
HSV-2: genital
Many strains of each
When is HSV-1 acquired?
Children, most inapparent 6-18 months
Ab formation is indicative of infection
When is HSV-2 acquired?
After puberty through sexual contact
Can also be acquired from an infected birth canal
What is gingivostomatitis?
HSV-1 infection
Vesicular lesions in all parts of oral cavity
What type of herpes infection infects the eyes?
Dendritic keratitis
Stromal involvement
Primarily HSV-1
What is eczema herpeticum?
Skin infection by HSV-1
Gladiatorum, herpetic whitlow, cold sores
How can HSV-2 infect the CNS of a neonate?
Infected birth canal –> transmission to neonate –> viremia –> brain
Can also affect the liver
How can herpes infect the CNS of an adult?
Spread along olfactory nerve –> temporal lobe (HSV-1)
How is the latent state of herpes virus established?
After primary infection HSV is transported up nerves to ganglia
After 14 days only HSV DNA present in cells, no viruses observed
What ganglia do HSV-1 and HSV-2 establish latency?
HSV-1 - trigeminal ganglia
HSV-2 - sacral ganglia
Can the latent virus be reactivated in the presence of antibody and cell-immediated immunity?
Yes, due to hormonal changes, chemo, immune system dysregulation, aging, UV light
How is the herpes virus reactivated from latency?
DNA in ganglia –> activation –> virus travels along nerves back to original site of infection, sequestered away from the immune system
What can result from frequent ocular herpes recurrences?
Corneal blindness and stromal scarring
What type of cancer is HSV-2 related to?
May be releated to incidence of cervical carcinoma
Could possibly potentiate HPV virus in causing cervical cancer
What skin infection can HSV initiate?
Erythema multiforme
What type of neurological effects can HSV initiate?
Idiopathic neuropathies
E.g. Bells palsy, trigeminal neuralgia, temporal lobe epilepsy
What are the three options for laboratory diagnosis of HSV?
Tzanck smear - scrape cells from base of lesion and stain
Virus isolation in cell culture
Serological - either Ab neutralization or PCR
How do you prevent neonatal infection of HSV?
C-section
What is chemotherapy used for?
Topical for keratoconjunctivitis or systemic for encephalitis
Nucleoisde analogs
What are the nucleoside analogs available for herpes infection?
Idoxuridine
Adenine arabinoside
Cytosine arabinoside
What is acyclovir used for?
Oral ACV reduces severity of recurring disease
Inhibits viral DNA polymerase
Inactive when administered, activated by viral thymidine kinase
What is Valacyclovir?
Taken orally and has better absorption characteristics
Converts to ACV
What is different about Peniciclovir?
Must be phosphorylated for activation and has a longer half life than ACV
What is the mechanism Foscarnet and Phosphonoformic acid (PFA)?
Inhibits viral DNA polymerase
What drugs does HSV form resistance against?
ACG and other nucleoside analogs
