Herpes Simplex Viruses 1 and 2 Flashcards
As a family, herpesviruses are
Large, double-strand DNA viruses whose icosahedral capsids are surrounded by lipid envelopes.
Herpesviruses are complex, encoding over 90 proteins that supply:
Attachment and fusion glycoproteins of the envelope; transcriptional regulators that redirect host RNA polymerase to viral genes; a viral DNA polymerase and associated enzymes for replication of the virus genome; capsomeres; and still other envelope glycoproteins required for virus spread from cell to cell.
A hallmark of herpesviruses is their ability to?
Establish latent infections in which the virus genome, but not virus progeny, is maintained in a quiescent state for the remainder of the host’s life.
Once infected with a herpesvirus?
A patient is infected for life and subject to recurrent infections when the latent virus reactivates to produce progeny once again.
Herpes simplex virus (HSV) serotypes 1 and 2 can be transmitted?
Sexually-transmitted viruses
HSV 1 and 2 replicate in?
Epithelial cells and reside latently in the trigeminal or sacral ganglia hence, they are termed neurotropic herpesviruses.
While HSV 2 principally causes?
Genital lesions, HSV 1 can too, and both viruses cause additional ailments.
Once attached, HSV directly fuses with the plasma membrane in a
pH-independent manner and the released nucleocapsid migrates to the cell’s nucleus where the genome is released.
Initial transcription/translation (“immediate early” expression) produces proteins that act
As transcriptional regulators that modify host RNA polymerase so that it preferentially transcribes viral genes over host genes.
“early” proteins whose roles are
To replicate the virus genome to produce progeny genomes.
Prominent “early” proteins include
A thymidine kinase and components of a virally-encoded DNA polymerase.
The thymidine kinase is important clinically for two reasons?
First, it is required to phosphorylate (and hence activate) acyclovir (ACV) and derivatives, the drugs of choice to treat most HSV infections. Second, thymidine kinase mutants are a problem during treatment because their spontaneous occurrence renders HSV resistant to ACV.
HSV resistant to ACV is particularly a problem in
AIDS patients dually infected with HSV.
The “late” class of proteins is produced; these encode the?
Capsomeres, envelope glycoproteins, and other structural proteins.
Virus assembly occurs in the?
Nucleus and the virus buds from the plasma membrane during release.
Because the same viral glycoproteins responsible for the initial fusion (entry) event are?
Also present in the plasma membrane of infected cells late in infection, infected cells may fuse with adjacent, uninfected cells.
HSV can spread from cell to cell without?
The formal release of virus progeny from one cell and subsequent attachment and penetration of a nearby cell leading to the formation of syncitia: giant cells with more than one nucleus.
Virus assembly in the nucleus and syncitium formation are the basis of?
A diagnostic test for HSV: the Tzanck smear, in which smears of cells taken from an ulcerous lesion (vesicle) are viewed under a microscope.
Nuclear assembly leads to the formation of?
Inclusion bodies in the nucleus.
If a Tzanck smear reveals multinucleated giant cells with nuclear inclusion bodies?
The infection is caused by a herpesvirus, presumably HSV.
Soon after primary infection in epidermal cells, HSV?
Establishes latency in peripheral sensory neurons.
Once latency established, the entire virus genome is?
Maintained extrachromosomally in neurons in 10-100 copies per cell, much like a plasmid in bacteria.
The only HSV gene expressed during the maintenance of latency is called?
LAT (latency-associated transcript) whose product is an RNA species that silences a subset of cellular genes to prevent apoptosis of the infected neuron.
Because only LAT is expressed?
No virus particles are produced during the maintenance of latency.
