Herpes Viruses: Herpes Simplex Flashcards
Herpes viruses are a family of large __(ss/ds) dna, __(enveloped/non-enveloped) viruses with a nucleocapsid
Herpes viruses are a family of large ds dna, enveloped viruses with a nucleocapsid
__ is usually associated with oral labial lesions, whereas __ is usually associated with genital lesions
HSV-1: likes oral cavity so it causes oral lesions.
**Think, you only have one mouth**
HSV-2: likes genital mucosa/mucosa so it causes genital lesions.
**Think: it takes 2 to make an STI**
Draw and describe the viral replication cycle of Herpes Simplex Virus
**what are 2 very unique things about the replication of HSV?**
**see image below for cycle**
Notice that this virus replicates in the nucleus, in contrast to many of the other viruses we’ve learned about so far
Also note that the viral envelope is take from the nucleus of the host cell, not the membrane!
How are HSV1 and HSV2 transmitted?
HSV1: mainly thru saliva (can also be oral to genital)
HSV2: mainly sexual (can also get oral transmission but pretty rare)
Also, from mother to chid at birth
Describe the pathogenesis of HSV (so from entry thru the mucosa, what happens and where does the virus lie dormant)
Which ganglia does HSV1, HSV2 lie dormant in?
Most infections are ___
Most infections are subclinical (asymptomatic)
Virus enters thru mucosal surface >> infects epidermis and dermis >> sensory/motor nerve endings >> ganglia (lies dormant here until reactivation)
HSV1: trigeminal ganglion
HSV2: lumbosacral ganglia
What can lead to reactivation of HSV infection?
Immunosupression
UV light (if you go to the beach in SC, you’ll get hit by that UV then you end up with HSV)
Trauma
Stress (remember how you had one last block?)
Describe the presentation of primary HSV1 infection
Acute onset of fever, malaise (basically the usual viral symptoms) and multiple vesicular lesions on inflammatory erythematous base
*again, note that many of these infections are asymptomatic*
A serious presentation of primary HSV1 infection in children is ___ (hint: too many ouches in the mouth)
Gingivostomatitis
- 4 days of fever, malaise, myalgias, cervical LAD >> painful lesions in the mouth, throat
- Difficulty eating, drinking, swallowing. Gingival bleeding. Bad breath
What is the adult equivalent of HSV1 gingivostomatitis seen in children?
Acute herpetic pharyngotonsillitis
-tonsilar exufate, severe sore throat, cervical LAD
__ is an HSV1 primary infection of the finger
Herpetic whitlow - occurs upon inoculation of HSV1 into break into the skin of the finger
More common in healthcare workers
*can happen with HSV2 as an STI - getting it from someone with genital herpes*
Another HSV1 primary infection resulting from a break in the skin is __ (hint: happens in modern day gladiators)
Herpes gladitorum
Occurs in wrestlers thru viral inoculation of abraded skin
Ulcerations on face, ear, neck; may affect trunk and extremities
Other syndromes that can result from HSV infection include __ (hint: a place called jaundice), and ___ (results from cranial nerve 7 infection)
HSV hepatitis (rare but deadly; happens in babies, immunosuppressed folks and pregaz)
Bell’s palsy
List the diseases of primary HSV1 infection
Gingivostomatitis/Acute herpetic pharyngotonsilitis
Herpetic whitlow
Herpes gladitorum
Less common: HSV hepatitis; Bell’s palsy
What could a patient present with before lesions appear in the case of HSV1 reactivation?
**think about where this bug lies dormant - the nerve ganglia, so you’re going to expect some kind of nerve related prodrome**
numbness, tingling 30min-48hrs before lesions appear
Oral HSV1 reactivation can present as ___
Which ganglia does HSV1 lie dormant in/does HSV1 reactivate from?
Recurrent oral labial lesions (so just recurrent cold sores)
Remember that this virus will lie dormant in the trigeminal ganglion (makes perfect sense because the trigeminal nerve branches control the mouth area anyway)
Another HSV1 reactivation syndrome is ___
Encephalitis - infection in temporal lobes of brain (reactivation from labial ulcers)
How would a person with HSV1 encephalitis present?
The usual encephalitis symptoms: headache, fever, confusion etc BUT can also aphasia because the infection goes to the temporal lobe
How do you Dx HSV encephalitis?
PCR of CSF**
CSF evaluation: WBCs, elevated protein and presence of RBCs
Imaging: MRI with classic necrotizing process in temporal lobe
What are the differences in presentation of esophagitis in a viral infection (e.g. with HSV) vs a fungal infection like candidiasis?
The difference between HSV and Candida esophagitis: more pain with swallowing in HSV as opposed to the difficulty swallowing caused by candida infection
**pain makes sense with this virus since its one that sits in the nerves**
What is another reactivation syndrome of HSV1 besides cold sores and encephalitis?
HSV-1 Esophagitis
What are the 3 manifestations of ocular herpes? (hint: it hits the corna, iris and retina)
HSV keratitis: Acute onset of pain, blurry vision, conjunctivitis; characterized by dendritic lesions on cornea
Herpes Iritis
Acute Retinal Necrosis: rare, necrotizing and progressive destruction of retina; leads to residual blindness and may require intraocular injections of antiviral drugs
Describe the presentation of HSV2 primary infection
Highly variable but for the most part you’re thinking about genital ulcers and inguinal lymphadenopathy:
**painful genital ulcers, dysuria, fever, inguinal lymphadenopathy, headache**
cervical and urethral involvement in women
**note that the inc period for this is 4 days**
HSV2 genital herpes can also lead to __ which is generally self ltd
Recurrence of this disease in pts is called __ and occurs more in women than men
Aseptic meningitis
Mollaret’s meningitis
How does neonatal herpes develop?
What are 3 manifestations of neonatal herpes?
Vertical transmission from mom infected with HSV2 (primary infection) usually during childbirth
Manifestations: skin, eyes and mouth syndrome, disseminated, and neurological
What is the primary manifestation of HSV2 reactivation?
Recurrent genital infection, can manifest as giant anogenital lesions and ulcers
How do you Dx HSV infection?
Generally clinical: you see it, you treat it
but also: Tzanck test: basically you scrape a skin lesion and stain the slide with Wright-Giemsa and you can see giant cells with nuclear inclusions (giant as in big, not as in multiple macrophages)
Viral culture (the infected cells are rounded on culture)/Shell vial culture
Direct Fluorescent Antibody (DFA) staining with an anti-HSV 1 or 2 mAb
PCR: mainly in HSV encephalitis
How do you treat HSV infection?
Describe the MOA of this treatment
Acyclovir (like you’re riding a cycle?)
works the same way that NRTIs do in HIV…see below (it’s all about that Thymidine kinase)
**note that you actualy use valacyclovir which is an oral prodrug with higher bioavailability but same effects as regular acyclovir**
Other option: Famciclovir (like you want a ride on my cycle, fam?): prodrug that works pretty much just like acyclovir and is cleaved to penciclovir (active drug)
How does HSV develop resistance to acyclovir?
Resistance: mainly in immunocompromised hosts with recurrent infections
also:
◦Reduced or absent TK activity
◦Altered TK activity -> decreased acyclovir phosphorylation
◦Altered viral DNA polymerase -> decreased affinity for acyclovir triphosphate