Flashcards in HSV 1 and 2 Deck (62)
Describe the structure of the herpesvirus family.
Large, ds-DNA viruses with icosahedral capsids that are surrounded by lipid envelopes
Why is the complexity of herpesviruses also their downfall?
Several effective anti-herpetic drugs have been developed because of all of the targets unique to the virus (limiting toxicity to humans too)
What is hallmark to herpesviruses?
They can establish latent infections in which the genome, but not progeny, is maintained in a quiescent state for the remainder of the hosts's life; Patients infected are subject to recurrent infections when the latent virus reactivates
What happens once HSV attaches?
HSV directly fuses with the plasma membrane in a pH-independent manner and the released nucleocapsid migrates to the cells nucleus and releases the genome
What does initial transcription/translation of HSV ("immediate early" expression) produce?
Proteins that act as transcriptional regulators that modify host RNA polymerase so that it preferentially transcribes viral genes over host genes = production of early proteins
What is the role of the early proteins of HSV?
They replicate the virus genome to produce progeny genomes
What are the prominent members of the early protein class of HSV?
A thymidine kinase and components of a virally-encoded DNA polymerase
Why is the thymidine kinase of HSV important clinically?
It is required to phosphorylate (and activate) acyclovir and derivatives (DOCs for most HSV infections). Next, mutations are a problem because their spontaneous occurrence renders HSV resistant to ACV (problem in AIDS patients)
Once progeny genomes are synthesized for HSV, what happens?
The late proteins are produced
What late proteins are encoded in HSV?
Capsomeres, envelope glycoproteins, and other structural proteins
Where does virus assembly of HSV occur?
In the nucleus and the virus buds from the plasma membrane during release
Because the same viral glycoproteins responsible for the initial fusion are also present in the plasma membrane of infected cells late in infection, what does that mean?
That infected cells may fuse with adjacent, uninfected cells which can lead to the format of syncitia: giant cells with more than one nucleus = HSV spread without release of virus progeny
Virus assembly in the nucleus and syncitium formation are the basis of what test for HSV?
Tzanck smear, in which smears of cells taken from ulcers are viewed, if Tzanck shows multinucleated giant cells with nuclear inclusion bodies the infection is caused by HSV
After the primary infection of HSV in epidermal cells happens, what happens?
HSV establishes latency in peripheral sensory neurons
Where is the genome of HSV maintained?
What is the only HSV gene expressed during latency? What does it produce?
LAT, whose product is an RNA species that silences a subset of cellular genes to prevent apoptosis of the infected neuron
What does LAT only being expressed mean?
No virus particles are produced, but a decline in cell-mediated immunity allows the virus to reactivate
What does reactivation of HSV lead to?
Recurrent infection in epithelial cells innervated by the latently-infected neurons (reactivation can kill the neuron = numbness)
What diseases does HSV 1 cause?
Herpes labialis (fever blister), Keratitis, Encephalitis
What diseases does HSV 2 cause?
Cervicitis, Vulvular vesicles, Penile Vesicles, Meningitis
Are most HSV infections self limiting?
HSV 1 and 2 can cause what kinds of infections?
Skin, ocular, and urogenital (HSV 1 is not only above the belt, and HSV2 is not only below the belt)
What is disseminated dz a problem in in regards to HSV?
Immunocompromised patients; neonates especially at risk, and infections can be fatal or severe
What are the symptoms of HSV?
Most asymptomatic, but when symptomatic multiple blisters form on the infected skin about two weeks following infections; blisters will rupture and produce severely painful open vesicles that can take 2 weeks to heal during a primary infection
When do recurrent HSV infections happen?
During lapses in immunity; resulting cold sore or genital lesion are limited in size and duration due to presence of neutralizing antibody
What are the symptoms of the oral infections caused by HSV 1 and 2?
Primary: gingivostomatitis, vescicles on lips, tongue, and facial skin around mouth
Recurrent: classical fever blisters
Primary and recurrent: low grade fever/headache
What are the primary symptoms of genital infections caused by HSV 1 and 2?
In males: vesicles anywhere on penis
In females: vesicles can be external or internal and can be difficult to detect even when present
What are the recurrent symptoms of genital infections caused by HSV 1 and 2? (This question is more asking how do you tell the difference between the two?)
Difficult to distinguish primary from secondary genital infections w/o knowing hx; generally fewer and heal quicker; HSV 2 genital infections recur more frequently than HSV 1
Can virus shedding occur without a recurrent genital lesion?