HSV 1 and 2 Flashcards

1
Q

Describe the structure of the herpesvirus family.

A

Large, ds-DNA viruses with icosahedral capsids that are surrounded by lipid envelopes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Why is the complexity of herpesviruses also their downfall?

A

Several effective anti-herpetic drugs have been developed because of all of the targets unique to the virus (limiting toxicity to humans too)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is hallmark to herpesviruses?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What happens once HSV attaches?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What does initial transcription/translation of HSV (“immediate early” expression) produce?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the role of the early proteins of HSV?

A

They replicate the virus genome to produce progeny genomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the prominent members of the early protein class of HSV?

A

A thymidine kinase and components of a virally-encoded DNA polymerase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Why is the thymidine kinase of HSV important clinically?

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Once progeny genomes are synthesized for HSV, what happens?

A

The late proteins are produced

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What late proteins are encoded in HSV?

A

Capsomeres, envelope glycoproteins, and other structural proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Where does virus assembly of HSV occur?

A

In the nucleus and the virus buds from the plasma membrane during release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

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?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Virus assembly in the nucleus and syncitium formation are the basis of what test for HSV?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

After the primary infection of HSV in epidermal cells happens, what happens?

A

HSV establishes latency in peripheral sensory neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Where is the genome of HSV maintained?

A

Extrachromosomally

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the only HSV gene expressed during latency? What does it produce?

A

LAT, whose product is an RNA species that silences a subset of cellular genes to prevent apoptosis of the infected neuron

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What does LAT only being expressed mean?

A

No virus particles are produced, but a decline in cell-mediated immunity allows the virus to reactivate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What does reactivation of HSV lead to?

A

Recurrent infection in epithelial cells innervated by the latently-infected neurons (reactivation can kill the neuron = numbness)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What diseases does HSV 1 cause?

A

Herpes labialis (fever blister), Keratitis, Encephalitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What diseases does HSV 2 cause?

A

Cervicitis, Vulvular vesicles, Penile Vesicles, Meningitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Are most HSV infections self limiting?

A

Yes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

HSV 1 and 2 can cause what kinds of infections?

A

Skin, ocular, and urogenital (HSV 1 is not only above the belt, and HSV2 is not only below the belt)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is disseminated dz a problem in in regards to HSV?

A

Immunocompromised patients; neonates especially at risk, and infections can be fatal or severe

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the symptoms of HSV?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

When do recurrent HSV infections happen?

A

During lapses in immunity; resulting cold sore or genital lesion are limited in size and duration due to presence of neutralizing antibody

26
Q

What are the symptoms of the oral infections caused by HSV 1 and 2?

A

Primary: gingivostomatitis, vescicles on lips, tongue, and facial skin around mouth
Recurrent: classical fever blisters
Primary and recurrent: low grade fever/headache

27
Q

What are the primary symptoms of genital infections caused by HSV 1 and 2?

A

In males: vesicles anywhere on penis

In females: vesicles can be external or internal and can be difficult to detect even when present

28
Q

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?)

A

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

29
Q

Can virus shedding occur without a recurrent genital lesion?

A

Yes

30
Q

What are the symptoms of both recurrent and primary genital infections?

A

FLS’s in addition to itching or burning skin in infected areas; muscle aches of the legs and buttocks (prodrome)

31
Q

What are the symptoms of ocular HSV infections?

A

Primary: Blepharitis and conjunctivitis seen in children
Recurrent: Keratitis can result in significant corneal scarring

32
Q

What are the symptoms of Encephalitis due to HSV?

A

It is the result of recurrent HSV 1 in adults but primary HSV 2 in neonates; presents as headache and fever –> confusion and seizures in adults; reactivation from trigeminal which then involves temporal lobes (70% mortality if untreated and 20-25 if treated early)

33
Q

What are the symptoms of meningitis due to HSV?

A

Occurs in 10% of primary HSV2; headache, stiff neck, vomiting (1 week resolution)

34
Q

What are the symptoms of neonatal HSV infections?

A

Usually the 1st - 2nd week postpartum, some are limited to skin, eyes, and mouth (they have the outcome, zoster like rash); others involve the CNS and are disseminated, 3/4 die or have significant sequelae

35
Q

How are HSV 1 and 2 transmitted?

A

Sexually; HSV2 is the more frequent genital infection

36
Q

What is the “above/below” the belt a reflection of?

A

The preferred tropism and the route of transmission of each organism

37
Q

How is Oral herpes transmitted to children?

A

Often from their parents; estimated 60% of US adults have HSV 1

38
Q

When are most HSV 2 infections dx’ed?

A

Between 20-29; 10% in males, 20% in females and 10% in young adults

39
Q

Is Herpes encephalitis rare?

A

Yes, 3/100000 adults; NOT more common in immunocompromised hosts; recurrence due to HSV 1
In neonate form it is from primary HSV 2 and about 25/100000 births

40
Q

How many neonatal infections of HSV are transplacental, with the rest occurring at time of birth?

A

5%

41
Q

If the mother current has a primary HSV infection what is the risk of transmission to the child? recurrent?

A

30%; 2-3% (maternal ab’s protective)

42
Q

What should be done if the mother has lesions at time of deliver?

A

C-section

43
Q

What is the diagnosis of genital herpes done by?

A

Culturing virus from lesions (3-10 days depending on the cytopathic effect)
Fluorescent antibody screening of virus grown in cell culture
PCR screening from vesicle swabs
Serology; can distinguish HSV 1 vs 2 but only indicates past infection
Tzanck smear

44
Q

What is the dx of herpes meningitis done by?

A

Mainly aimed at ruling out bacterial source; CSF is cultured to look for CPE to indicate viral origin = self limiting

45
Q

What is the dx of herpes encephalitis done by?

A

Cultures of CSF rarely positive here, serology also too late here, normal EEG rules OUT herpes encephalitis
Confirmation achieved by PCR of genome fragments from CSF then used in a southern blot (result in 24 hrs)

46
Q

What is dx of neonatal herpes done by?

A

Dx as for other disease, in addition check liver enzymes for disseminated disease evidence

47
Q

What is the DOC of herpes treatment?

A

ACV

48
Q

What are ACV drugs?

A

Deoxyguanosine analogs that prevent viral genome replication by inhibiting the viral DNA polymerase

49
Q

Are ACV drugs prodrugs?

A

Yes, they require three phosphate groups to become activated

50
Q

What adds the phosphate groups to ACV?

A

First by a viral kinase (HSV thymidine kinase), then 2 by cellular kinases

51
Q

Will cellular kinases add the first phosphate?

A

No, so ACV is never made into active form in a non-infected cell

52
Q

What is significant about mutations in thymidine kinase?

A

Render ACV inactive; problem in AIDS patients

53
Q

What are the ADEs of ACV tx?

A

Nausea, skin rash, diarrhea, renal failure, seizures, disorientation (last 3 in high dose therapy)

54
Q

What are Vidarabine and Trifluoride

A

DNA analogs that inhibit viral DNA polymerase

55
Q

What is foscarnet?

A

Pryophosphate analog that blocks the pyrophosphate-exchange site preferential on the viral DNA polymerase (blocks viral DNA replication)

56
Q

Does Foscarnet require phosphorylation?

A

No, so it is not affected by thymidine kinase mutations and is a backup to ACV if it fails

57
Q

What is Docosanol?

A

An OTC med for cold sores, can lessen the extent

58
Q

What does Docosonol do?

A

Modifies host cell membrane so that the virus envelope cannot fuse with the plasma membrane

59
Q

What is the specific Tx for genital herpes?

A

Low dose ACV from first sign of outbreak until completed, A single day, high dose of Famciclovir is FDA-approved if taken w/in first 6 hrs of sx
Daily suppressive therapy of low dose ACV reduces freq + length of virus shedding/spread (expectant mothers)
Educate to recognize symptoms to reduce spread

60
Q

What is the specific Tx for herpes encephalitis?

A

IV, High dose ACV for 10 days - 3 weeks at first sign of illness

61
Q

What is the specific Tx for neonatal/congenital herpes?

A

IV, high dose ACV for 14 days in skin, eye, mouth infections and for 21 days in CNS infections

62
Q

Is there an HSV vaccine?

A

No