Human Herpesvirus Flashcards
What is the structure of the herpesvirus?
DNA Caspid Tegument Envelope Glycoprotein spikes Icosahedral caspid surrounding dsDNA Virus size 120-200nm Have 80 genes coding for 100 proteins
How to classify human herpesvirus?
alpha herpesviruses: Epidermal/neuronal viruses with a wide host range
- Type 1 Herpes Simplex - Virus HHV-1
- Type 2 Herpes Simplex Virus HHV-2
- Varicella-Zoster Virus (VZV) HHV-3
β-herpesviruses: Slow growth, primarily in T-cells and leukocytes - Cytomegalovirus (HCMV) HHV-5 - Human Herpesvirus 6 HH V-6 - Human Herpesvirus 7 HHV-7
γ-herpesviruses: primarily B-lymphocytes:
- Epstein-Barr virus (EBV) - Barr virus (EBV) HHV 4
Human Herpesvirus 8 HHV-8
What does does Herpes Simplex Virus 1&2 cause?
Oropharyngeal and genital herpes
What does Varicella-Zoster Virus (HHV-3) cause?
Chicken-pox (Varicella) / Shingles (Zoster)
What does Epstein
-Barr Virus (HHV-4) cause?
Infectious mononucleosis (glandular fever), Burkitt’s lymphoma, nasopharyngeal carcinoma
What does Cytomegalovirus (HHV-5) cause?
Cytomegalic inclusion disease in utero
What does HHV-6 cause?
Exanthem subitum, fatigue syndrome
HHV-7 causes what?
Pityriasis rosea?
HHV-8 causes what?
Kaposi’s sarcoma (in AIDS pts)
What does HSV1 mainly cause?
Oral infecs
What does HSV2 mainly cause?
Genital infecs
How does HSV 1 cause herpetic gingivostomatitis?
Virus enters trigeminal sensory neurones - migrates to trigeminal ganglion
HSV1 becomes latent in trigeminal ganglion but dormant in 50% of cases
Migrates to peripheral nerve endings where active viral particles are shed
What reactivates a herpes simplex infection?
UV light
Stress
Illness
Immunosuppression
HSV 2 can cause herpes labialis - features of this?
Lesion (on edge of lip) resolves
Virus lays dormant in trigeminal ganglion until reactivated
What causes a primary HSV infection?
Source of virus:
- Skin lesions
- Saliva
- Usually HSV1
Passive immunity
From maternal
Antibody in infancy
Source of virus:
- Genital lesions
- Genital secretions
- Usually HSV2
What percentage of the primary HSV infections are symptomatic and asymptomatic?
Asymptomatic = 90-99% Symptomatic = 1-10%
What occurs when there is establishment of the HSV latent infection?
Reactivation of latent virus and 2ndry/recurrent infection
Incidence of herpetic gingivostomatitis?
Very common
Mainly affects young children
Sometimes young adults - more severe
Clinical features of herpetic gingivostomatitis?
Incubation period 3-10 days Duration 5-14 days Multiple vesicles - rupture to form extensive sloughing ulcers Gingivitis with erythema and sloughing Malaise, pyrexia, lymphadenopathy
How to diagnose herpetic gingivostomatitis?
Clinical appearance
Main diagnostic difficulty with erythema multiforme
How to investigate herpetic gingivostomatitis?
Not normally done
Rising antibody attire/presence of IgM antibodies
Viral culture or PCR
What is the basic method of PCR?
Denature DNA to single strands at 95 degrees
Annealing of specific primers to DNA at 55 degrees
Extension by polymerase at 72 degrees
Amplification - Repeat 30-35 times
What occurs by the end of each PCR cycle?
Amount of DNA has doubled
What occurs by the end of 30 cycles of PCR?
1 billion molecules from the one you started with
How to manage herpetic gingivostomatitis?
Acyclovir (200mg 5x daily for 5 days) if found early or immunocompromised Fluids and soft diet Analgesics/antipyretics (paracetamol) Local antiseptics (chlorhexidine) Topical analgesics (difflam) X-infection control
How does acyclovir work?
HSV thymidine kinase (TK) phosphorylates guanosine (G) when HSV DNA replicates
ACV is phosphorylated to ACVP
Inhibits virus replication
Is a chain terminator
Herpes labialis clinical features?
Prodromal irritation
Vesicles at or near mucocutaneous junction of lips
Crusting lesions lasting 7-10 days
Usually re-occurs at same sites
Rarely: may occur, intra-orally, in nose or elsewhere on skin
How to manage herpes labialis?
Acyclovir cream 5% if used very early
OTC drying and antibacterial agents
Prophylactic treatment of herpes simplex virus 2?
Rarely justified
Prophylactic acyclovir will prevent lesions in the immunocompromised or those susceptible to erythema multiforme
What does acyclovir do in herpes labialis?
Prophylactic - oral AVC (600-1000mg/day in 2 doses) is effective
Reduces:
- Duration of pain by 1.4 days
- Time to lesion crusting by 2.1 days
- Occurrence of new lesions by 50%
- Mean number of recurrences over a 4 month observation period
INCREASES mean time to next recurrence from 46 to 118 days
What is herpetic whitlow?
Herpetic infection of the fingers from handling the oral tissues of someone with active 1 or 2 herpes simplex lesions
Features of herpetic whitlow?
Very painful
Difficult to treat
Prevention better than cure - wear gloves
Features of HSV encephalitis?
Mainly affects frontal lobes of the brain
70-80% mortality if untreated
Of survivors, only 3% return to normal
Usually people >50yrs (HSV-1) and neonates (HSV-2) affected
Signs and symptoms of HSV encephalitis in adults (HSV-1)?
Adults
Headache and behavioural changes over several days
Fever
11% have history of recurrent HSV infecs
Signs and symptoms of HSV encephalitis in neonates (HSV-2)?
Adults Skin rash, lesions and CNS symptoms Virus present in liver, lung and adrenal glands Resp distress Fits and convulsions Raised intracranial pressure
Incidence of HSV encephalitis in neonates?
1 per 300,000
What do HHV-3 and HSV1 and 2 have in common?
Similarities in structure and infection
What happens if you get varicella-zoster virus (HHV3)?
Chicken pox/varicella (primary infec) = Dormant in the dorsal root/trigeminal ganglion = Remains dormant OR Reactivation: Age (70% >50yrs) Stress Illness Immunosuppression
= Herpes Zoster (2ndry infec)
Seldom reoccurs
Where does herpes zoster 2ndry infection (shingles) most commonly affect?
What does it look like?
Chest and back only on 1 side (opposite to the side infected)
= Blisters, rash
Herpes zoster causing oral disease most commonly affects what nerve? What are the 3 phases?
Trigeminal nerve Phases: - Preherpetic neuralgia - Rash - Post herpetic neuralgia
Explain the pre-herpetic neuralgia?
Pain in the distribution of the affected division of the trigeminal nerve
Prior to the development of the rash
May mimic dental pain
Explain the rash phase of herpes zoster?
Unilateral vesicles in the distribution of a branch of the trigeminal nerve:
- Opthalmic
- Maxillary
- Mandibular
Vesicles break down to form:
- Ulcers
- Crusting lesions
Lasts 2-3 weeks
What eye problems can herpes zoster cause?
Glaucoma
Cataract
Double vision
Scarring of the cornea
How to manage herpes zoster?
Acylovir 800mg 5 x daily for 7 days if seen soon after lesions develop
Analgesics
Ophthalmic referral if eye involved
Avoid contact with children
Alternatives to acyclovir:
- Valaciclovir 1g 3xdaily for 7 days
- Famciclovir 250mg 3xdaily for 7 days
Explain post herpetic neuralgia of herpes zoster?
10% of pts = unpleasant intractable burning pain in the distribution of the affected nerve
More common in elderly
Effective early treatment of zoster may decrease risk of neuralgia
Treat pain with tricyclic antidepressants and neuropathic pain drugs
What is HHV-4 (EBV) associated with?
Infectious mononucleosis (glandular fever) - acute 1 infec with EBV)
Burkitt’s lymphoma - a B cell malignancy
Nasopharyngeal carcinoma - epi cell malignancy
Oral hairy leukoplakia - seen in AIDS pts and some transplant recipients
Where does primary infection EBV replicate and establish latency?
Replicates in oropharyngeal epi cells
Establishes latency in B lymphocytes
What is EBV latent infection of B lymphocytes necessary for?
Virus persistency
Subsequent replication in epi cells
Release of infectious virus into saliva
What percentage of the world’s population are infected with EBV?
95%
Symptoms of infectious mononucleosis EBV?
Most are asymptomatic
Sore throat
Swollen cervical lymph nodes
Mild fever
EBV in the oral environment - infectious mononucleosis signs?
Petechiae on soft palate
Creamy exudates on fauces
Cervical lymphadenopathy
What is burkitt’s lymphoma?
Malignant, B cell lymphoma of high prevalence in children in tropical Africa at elevations below 1500 metres where malaria is present
Usually affects jaw bone - tumour mass
How to treat burkitt’s lymphoma?
cyclophosphamide (chemo)
What can HHV-5 (Cytomegalovirus) rarely cause in healthy individuals?
Glandular fever like illness
Salivary gland swelling
What can HHV-5 (Cytomegalovirus) cause in immunocompromised/AIDS pts?
Large ragged oral mucosal ulcers
Salivary gland swelling
Retinitis
What can HSV-8 cause in AIDS pts?
Kaposi’s sarcoma
