Herpesviruses HSV 1, HSV 2 & VZV Flashcards
Describe the features of Herpesviruses
dsDNA linear, icosahedral, enveloped
Inactivated with: detergents, acid, drying (b/c they’re enveloped)
Herpesviruses have what kind of infections
Lytic and Latent
The _________ response in all herpes infections is critical to keeping the virus in check
CD8-CTL
All herpesviruses have _________ infections
systemic/generalized
The herpesvirus _______ class of antivirals stops viral DNA replication
acyclovir
Once activated by a viral thymidine kinase, it is used by the viral DNA polymerase and causes viral DNA chain termination
The acyclovir antivirals need to be activated by a protein found in an infected cell, a ___________
viral thymidine kinase
*The drugs should only act on cells that are infected by the virus
What is Valacyclovir? Where is it metabolized? Why is it used?
A prodrug of acyclovir.
It is metabolized in the body to acyclovir.
It is used because it has a longer 1/2 life in the body. You can take fewer pills a day
What is Famciclovir?
The oral prodrug of the topical ointment penciclovir and is often used interchangeable with acyclovir and valacyclovir
What is Ganciclovir?
Used for CMV infections. It also has a prodrug that has a longer 1/2 life in the body Valgancicloir. (However, ganciclovir has more side effects than acyclovir. When treating CMV, ganciclovir/valganciclovir is used because CMV does not activate acyclovir and penciclovir very well.)
Where does resistance to the acyclovir class of drugs usually occur?
In the viral thymidine kinase
When can drugs not phosphorylated by the viral kinase be used?
Can be used if resistance develops. They also prevent viral DNA replication
List the two types of HSV
HSV-1 and HSV-2
T/F: HSV-1 and HSV-2 are identical viruses
False - they are similar but not identical viruses (50% genetic identity between the two)
T/F: A person can only be infected with one HSV virus at a time
False - a person can be infected with both HSV-1 and HSV-2
Both HSV-1 and HSV-2 infect mucosal epithelial cells, cause lesions, and become latent in nerve ganglia, __________ for oral infections, and __________ for genital infections
trigeminal ganglia; sacral ganglia
What happens to the HSV viruses during latency?
The virus expresses a range of suppressive miRNA but no proteins (no protein to present in MHC I, thus, no killing by CTLs). These miRNA’s suppress viral lytic gene expression, called latency-associated transcripts, LAT
Remember, HSV and VZV will go up the nerve via _____________ and lay dormant latent
retrograde axial transport
*No virus is produced in latency, but the cell can reactivate and produce virus
Which HSV causes genital herpes? Oral herpes?
Either virus can cause genital herpes
The vast majority or oral herpes is caused by HSV-1
Why is the number of HSV-1 causing genital herpes increasing?
It used to be that almost everyone got HSV-1 in childhood before they became sexually active, and
oral HSV-1 protects against acquiring genital HSV-1. Now, fewer and fewer people are positive for HSV-1
before becoming sexually active, and oral sex spreads HSV-1 to the genital tract.
___________ the name for the first infection with oral HSV
Gingivostomatitis
What is the primary causative agent for Gingivostomatitis? How does it work?
HSV-1
It infects mucosal epithelium with lytic infections causing sores, then travels up to trigeminal ganglion where it remains latent.
List the symptoms of Gingivostomatitis
-Gingivitis and vesicles on the buccal mucosa, also on the tongue, hard palate, gingiva, lips and face
-Vesicles break down into ulcers and then crust over on lips and face but usually don’t scar
-It lasts 1-2 weeks and can be very painful. (Children may become dehydrated)
-There is often fever and enlarged lymph nodes
___________ is the term for any reactivation/recurrent oral herpes after the primary infection
Herpes labialis
(It is usually less severe, has fewer lesions, and appears in the same place as primary lesions)
What can trigger recurrence of herpes labialis
Stress
UV light
Menstruation
Dental procedures (such as oral surgery and root canals)
T/F: Generally, herpes labialis is less severe, with no fever or lymph node swelling
True
Oral asymptomatic shedding of _______ is common in people who have been infected with herpes labialis
HSV-1
A large proportion of the US are seropositive for _________, almost all from genital infection
HSV-2
**The vast majority of them do not know they are HSV2+. And there is an increased amount of people infected genitally with HSV-1
T/F: Asymptomatic infections of genital herpes are uncommon
False - asymptomatic infections are common. It is most common to get HSV from an asymptomatic shedding partner
Where are infections and lesions present with genital herpes?
Genital epithelium
Upper thighs
Anal area
(Primary outbreak is the worst and can result in lymph node swelling, fever, and more sores than will be present in reactivation events)
T/F: HSV-2 tends to cause more recurrences and asymptomatic shedding than genital HSV-1
TRUE
What can be taken for oral and genital recurrent herpes sores?
Acyclovir, Valacyclovir, or Famciclovir can be taken
prophylactically or at the first signs of an outbreak. Acyclovir, valacyclovir, or famciclovir can also be taken
daily to help prevent outbreaks and transmission but do not entirely stop asymptomatic shedding
What is Herpetic Whitlow?
Herpetic lesions on the finger, common in dentist and other HCW.
Herpetic whitlow lesions can shed _____ and spread the virus to other people
HSV
Are recurrences of herpetic whitlow common?
Yes
What are preventative measures for herpetic whitlow?
Gloves and handwashing
What can be taken to reduce symptoms of herpetic whitlow?
Topical acyclovir or penciclovir, or oral acyclovir, valacyclovir, or famciclovir
What can cause Ocular Herpes?
Reactivating oral herpes going to the eye or spread by touching the eye and contaminating it with HSV-1 (more common in people who wear contacts)
What are symptoms of ocular herpes
Most of the time is resolves without a problem. But can cause more sever infections that scar the cornea. Ocular herpes can also recur with a higher chance of some permanent vision less.
What is treatment for ocular herpes
antiviral eye drops and/or oral acyclovir
Almost all cases of Herpes Simplex Encephalitis are with ____
HSV-1
How does Herpes simplex virus spread?
Travels up olfactory or trigeminal nerves to the temporal or frontal lobes of the brain. (This can happen during primary infection or during the reactivation of the virus). The virus replicates, causing necrosis of brain tissue
How do you treat herpes simplex?
Prompt tx is needed with acyclovir given intravenously.
Without acyclovir
treatment, there is a high fatality rate, which is drastically reduced with acyclovir, but
survivors can have neurological deficits.
How is neonatal herpes caused?
-Most cases caused by HSV-2, but HSV-1 cases are rising
-Can also be caused by the reactivation of an existing infection close to labor
How is neonatal herpes spread?
Spread from vertically. Most cased are due to primary infection while pregnant
How is neonatal herpes treated?
The use of acyclovir in an infant can drastically reduce mortality.
(If there are genital lesions close to delivery, it is recommended to deliver by a cesarian. If there are
lesions anytime during pregnancy, acyclovir is recommended starting at 36 weeks of pregnancy.)
How is Varicella Zoster Virus/Chickenpox spread?
Via respiratory droplets; lesions are also contagious
Where are most Varicella lesions located?
on the face and trunk, with fewer on the extremitites
What is a defining feature of Varicella?
Vesicular rash; lesions are present in all stages, from just erupted to crusted over
(Varicella can be more sever in adults, pregnant women, and the immunocompromised, with the most common risk being pneumonia)
Varicella is usually latent in….
dorsal root and cranial nerve, and trigeminal ganglia
Do not give _____ to children with chickenpox or influenza; it may cause Reye’s syndrome
Aspirin
There is a high risk for pneumonia with high mortality rate when pregnant and infected with ______
varicella
*The mortality can be lowered with tx
If infected with Varicella in the first trimester, what can happen?
Can cause severe congenital disabilities
What happens if varicella symptoms occur before delivery?
Before a maternal antibody response can occur and transfer to the fetus, the baby can contract varicella. The baby can have disseminated disease
(Luckily, congenital varicella and disseminated infection of newborns are very rare)
Reactivation of varicella virus along dermatomes causes _________
Herpes Zoster/Shingles
Usually 1-3 adjacent dermatomes, thoracic, ophthalmic, and cervical are most common
T/F: Herpes Zoster lesions can be infectious and cause the primary infection of chickenpox (varicella)
True
What is herpes zoster opthamalicus?
Shingles outbreak near the eye
Prompt tx with antivirals is needed b/c the infection can travel to the eye leading to permanent vision loss
About 1/3 of people with shingles can develop…..
Post-herpetic neuralgia (PHN); this is where you continue to have mild to severe pain after the resolution of lesions. PHN may last weeks, months, and sometimes years
Shingles occur primarily in people over 50 when the ____ response for _____ seems to be waning
CTL; VZV
How do you prevent Varicella?
There is an attenuated vaccine recommended for all children. Need two shots for complete protection
Because the varicella/chickenpox vaccine is an attenuated virus, it is contraindicated in ___________
immunosuppressed or pregnant people
What vaccine is approved for shingles?
A subunit vaccine Shingrex (envelope glycoprotein E) with an adjuvant. It is very efficacious in preventing shingles and post-herpetic neuralgia. It is recommended for all people over 50 y/o who’ve had chickenpox
What happens if you’re exposed to chickenpox and previously not vaccinated?
-If given early enough (w/in 72 hours of exposure) the vaccine can afford some protection.
-If contraindicated for the live-attenuated vaccine, varicella IgG (VeriZIG) can be given to help prevent infection
T/F: In people with HIV, there can be more recurrent oral and genital outbreak that are more severe with HSV-1 and HSV-2
TRUE
T/F: People with HIV are much less likely to get shingles
FALSE - they are much more likely to get shingles at an earlier age and do worse if they contract chickenpox
