5/27- Human Herpes Virus (HHV) 2 Flashcards
Three subfamilies of herpesvirus?
Alpha
Beta
Gamma
Viruses within alpha subfamily of herpesvirus?
H. simplex type 1 (HHV1), 2, and 3
Viruses within beta subfamily of herpesvirus?
Cytomegalovirus (HHV5)
HHV 6
HHV 7
Viruses within gamma subfamily of herpesvirus?
Epstein-Barr (HHV4)
KSHV (HHV8)- Kaposi’s
Characteristics of alpha subfamily?
- Rapid growth
- Variable host range
- Latent in ganglia
Characteristics of beta subfamily?
- Slow growth
- Persist in CD4+ cells, monocytes/macrophages, mesenchymal cells
Characteristics of gamma subfamily?
- Poor growth/abortive
- Latent in lymphocytes
Question:
Acute infxn followed by complete elimination from the host is characteristic of which one of the following viruses?
A. Influenza virus
B. Herpes varicella-zoster virus
C. BK virus
D. Adenovirus
Answer:
Acute infxn followed by complete elimination from the host is characteristic of which one of the following viruses?
A. Influenza virus
B. Herpes varicella-zoster virus
C. BK virus
D. Adenovirus
Common targets of antiviral therapy of herpesvirus?
Genomes encode numerous enzymes involved in NA metabolism and DNA synthesis
Is herpes lytic or lysogenic?
Production of infectious progeny results in lysis of infected cell
Clearance or latency for herpes?
All persist and may reactivate; reactivation may/may not be associated with disease
What molecules are required for infectivity?
gB and gD (gG is type specific)
(gB is most important ‘neutralizing epitope’)
Epidemiology of HSV?
- Worldwide
- Seroprevalance varies by age and SES
- more HSV1 in lower SE groups; earlier 1’ infxn
- more HSV2 after puberty
Transmission of herpes virus?
Direct contact
Pathogenesis of 1’ herpes infxn?
- Penetrates into skin
- Local replication and entry of virus into cutaneous neurons
- Centripetal migration in axon of uncoated nucleocapsids
- Synthesis of infectious virions
- Centrifugal migration fo infectious virions to epidermis
When is viremia most common with HSV?
- Among pts with 1st episode of genital HSV
- Especially women with HSV 2 infection
What cells are involved in the immune response for HSV? Other lines of immune defense?
- NK cells
- Cell-mediated immunity with CD8+ T cells
Other:
- TLRs
- Serum antibodies (neut, CF, IF, ELISA)
- peripheral mucosal immune system
Most reactivations of herpes in healthy people are long/symptomatic or short/asymptomatic?
Short/asymptomatic
Where does the herpes virus remain latent?
Trigeminal ganglion
What percentage of 1’ herpes infxns are asymptomatic?
> 90%
Common disease syndromes for HSV?
- Gingivostomatitis -> fever blister (HSV 1 > 2)
- Keratitis
- Whitlow
- Encephalitis
- Cutaneous herpes (‘herpes gladiatorum’)
- Genital herpes (now HSV1 > 2 in US)
- Neonatal herpes
What layer are the vesicles with HSV infxn?
Intra-epithelial
What do HSV lesions look like?
Grouped vesicles on erythematous base
Symptoms of herpetic gingivostomatitis?
- Fever
- Malaise
- Myalgias
- Irritability
- Pain
- Tender lymph nodes
Signs:
- Typical lesions on: tongue, palate, lip, gingiva, face, pharynx
- Adenopathy
Symptoms of herpetic keratitis
- Pain
- Blurred vision
- Conjunctivitis
- Dendritic lesions of cornea
- HSV keratitis is MCC of corneal blindness in the US!
Symptoms of herpetic whitlow?
Lesions of fingers may result from autoinoculation or from occupational/other exposure. (may be confused w/ pyogenic bacterial infxn)
What is the MCC of acute, sporadic viral encephalitis in the US?
Herpes simplex virus
Symptoms of herpes simplex encephalitis?
- Fever
- Headache
- Focal neurologic Sx/signs
Symptoms of genital HSV2 infxn (1’ and recurrent)
1’: fever, headache, malaise, and myalgia; pain, itching, inguinal adenopathy, vaginal & urethral discharge, possible acute urinary retention and aseptic meningitis
reactivation: often mild or asymptomatic
% breakdown of different types of vertical transmission?
90% perinatal
5-8% congenital
few postnatal
Symptoms of neonatal herpes?
Involves skin, viscera, and/or CNS
What is eczema herpeticum?
Widespread lesions that may develop in people who have underlying skin disorders such as eczema
Question:
Direct contact with characteristic lesions in which one of the following clinical settings does NOT transmit infection to susceptible individuals?
A. Genital herpes
B. Erythema infectiosum (“Fifth Disease”)
C. Condyloma accumulata (genital warts)
D. Orf (parapox)
Answer:
Direct contact with characteristic lesions in which one of the following clinical settings does NOT transmit infection to susceptible individuals?
A. Genital herpes
B. Erythema infectiosum (“Fifth Disease”)
C. Condyloma accumulata (genital warts)
D. Orf (parapox)
Mechanisms of latent HSV?
- Viral DNA persists as an episome
- Latency-associated transcript encodes microRNA that is anti-apoptotic (no symptoms/lesion/virus)
Reactivation from trigeminal ganglia results in what?
- No symptoms, or
- Intraoral mucosal lesions of lip/face (cold sore)
What is herpetic stomatitis
Extensive lesions that may develop in pts who are immunocompromised (gross tongue pic)
Detection/Diagnosis of HSV?
- Tzanck prep to look for multinucleated giant cells
- Fluorescent antibody staining
- Isolation in tissue culture (needle aspirate to see cytopathic effect of HSV in tissue culture)
- Serodiagnosis (higher in 1’ infxn, no rise w/ recurrent infxn, significant rise in CSF/serum with encephalitis)
Question:
A 25 yo sexually-active woman presents with a 2 day Hx of headache and burning on urination. PE reveals genital ulceration; several vesicular lesions are noted. Which of the following is LEAST likely to provide useful diagnostic info?
A. Tzanck smear of lesion scrapings
B. Rapid antigen test of lesion swabs
C. Viral culture
D. Routine urine for culture and sensitivities
Answer:
A 25 yo sexually-active woman presents with a 2 day Hx of headache and burning on urination. PE reveals genital ulceration; several vesicular lesions are noted. Which of the following is LEAST likely to provide useful diagnostic info?
A. Tzanck smear of lesion scrapings
B. Rapid antigen test of lesion swabs
C. Viral culture
D. Routine urine for culture and sensitivities (routine is bacteria)
Peak epidemic season(s) fro VZV?
Winter
Main transmission of VZV?
Respiratory
What factors could contribute to reactivation of varicella?
- Aging
- Radiation
- Surgery/trauma
- Immunosuppression
Pathogenesis of Varicella?
- Incubation period
- Mucosal inoculation: aerosol or contact
- Replication in regional nodes
- VZV-infected T cells enter capillaries
- Primary T-cell viremia
- Replication in liver and spleen
- Secondary T-cell viremia
- Development of rash after 24-72 hours
Symptoms of Varicella/Chickenpox?
- Usually mild
- Fever and malaise
- Followed by development of rash (24-72 after infxn) (itchy rash)
What can complicate varicella infxn?
2’ infxn with Group A strep
Varicella pneumonia occurs in what pts?
- More often in adolescents and adults
- Immunocompromised
When is varicella fatal?
- immunocompromised children (e.g. SCID)
Greatest risk of maternal infxn for vertical transmission of varicella?
Maternal dz occurring 5 days before or up to 48 hrs postpartum
What is herpes zoster (HZ)?
Reactivation dz associated with VZV infxn (aka Shingles)
What increases risk of HZ?
- Aging
- Immunosuppression
How many (%) people develop HZ in lifetime?
20% (1/2 of these by age 85)
What debilitating symptom may accompany HZ? %?
Postherpetic neuralgia (PHN) in 20-50%
Characteristics of HZ rash?
- Unilateral
- Dermatomal
- Often thoracic
Common organ involved with HZ?
Eye (ophthalmoplegia)
Antivirals and other methods used to treat and prophylax for HHV3?
Antivirals:
- Acyclovir
- Famciclovir
- Valacyclovir (other topical and parenteral drugs)
Live attenuated vaccine
Varicella-zoster immunoglobulin (VZIG) to prevent/modify dz after exposure
Strict infxn control msrs to prevent nosocomial spread
Who should receive the VZV vaccine?
- Healthy susceptible children and adults
- High dosage vaccine for prevention of shingles in people > 60 yo
Question:
Which of the following diagnostic tests is LEAST likely to establish the diagnosis of recurrent VZV infection (or shingles)?
A. Viral culture of vesicular fluid
B. Detection of nucleic acid via PCR of lesion scrapings
C. Acute IgG titer vs. VZV
D. Tzanck smear of lesion scrapings
Answer:
Which of the following diagnostic tests is LEAST likely to establish the diagnosis of recurrent VZV infection (or shingles)?
A. Viral culture of vesicular fluid
B. Detection of nucleic acid via PCR of lesion scrapings
C. Acute IgG titer vs. VZV
D. Tzanck smear of lesion scrapings
Question:
A 52 yo female presents w/ 2 day Hx of pain on R side of chest. New rash this morning- unilateral, vesicular in T8 distribution. Which statement about condition is CORRECT?
A. No treatment is available
B. No vaccine is available which could have prevented this condition
C.. The lesions are potentially infectious
D. These lesions are probably the result of direct contact with a persons who had varicella within the last 3 wks
Answer:
A 52 yo female presents w/ 2 day Hx of pain on R side of chest. New rash this morning- unilateral, vesicular in T8 distribution. Which statement about condition is CORRECT?
A. No treatment is available
B. No vaccine is available which could have prevented this condition
C.. The lesions are potentially infectious
D. These lesions are probably the result of direct contact with a persons who had varicella within the last 3 wks
