Human Herpesviruses

Question 1

Herpeton

Answer 1

• greek for creep
  Icosahedral capsid surrounding ds DNA
  Virus size 120-200 nm
  80 genes coding for 100 proteins

Question 2

beta herpes

slow growth in t cells and leukocytes

Answer 2

cytomegalovirus
human herpesvirus 6
human herpesvirus 7

Question 3

gamma herpes virus

Answer 3

epstein barr

human herpesvirus 8

Question 4

herpes simplex virus 1+2

Answer 4

oropharyngeal and genital herpes

Question 5

varicella zoster

Answer 5

chicken pox / shingles

Question 6

epstein barr virus

Answer 6

infectious mononucleosis, burkitt’s lymphoma, nasopharyngeal carcinoma

Question 7

cytomegalovirus

Answer 7

Cytomegalic inclusion disease in utero (newborns and immunocompromised)

Question 8

HHV 6

Answer 8

Exanthem Subitum (6th disease)?
HHV-7 HHV-8
Fatigue syndrome

Question 9

HHV 7

Answer 9

Pityriasis rosea?

Question 10

HHV 8

Answer 10

Kaposi’s Sarcoma (in AIDS patients)

Question 11

Infection and replication

Answer 11

Hijacks host cell machinery
Viral cell injects DNA into host cell and gets uncoated
Transcription of DNA
Translation of viral proteins
Factor produced with has high affinity for host cell DNA polymerase - alters specificity
Viral DNA replicated and reinserted into viruses –> mature viruses
Viruses break out of nuclei and cytosis occurs

Question 12

HSV1

Process
Symptoms

Reactivation

Answer 12

Mainly oral infections
- herpetic gingivostomatitis

• virus enters trigeminal sensory neurones and affect sensation and motor fx
• migrates to trigeminal ganglion
• 50% becomes reactivated and migrates to peripheral nerve endings
• causes 2ndary pathology
• shedding of viruses at epithelial level
• herpes labialis - cold sores
• XS UV light
• stress
• illness
• immuno suppression

Lesion resolves
Virus lays dormant again in trigeminal ganglion until reactivated

Question 13

HSV 2

Cause

Answer 13

Mainly genital infections

Question 14

Natural history of HSV infections

source of virus -

symptoms

Answer 14

Primary infection
Skin lesions
Saliva

genital lesions
genital secretions
90-99% asymptomatic
1-10% symptomatic

Question 15

primary HSV

Answer 15

Very common

Mainly affects young children and young adults

Question 16

primary HSV

Answer 16

Very common

Mainly affects young children and young adults

Question 17

Herpetic gingivostomatitis
Clinical features

diagnosis

investigation

Answer 17

Incubation period 3-10 days
Duration 5-14 days 
multiple vesicles rupture to form sloughing ulcers
gingivitis with erythema and sloughing 
malaise, pyrexia and lymphadenopathy 

Diagnosis:
Typical clinical appearance
Main diagnostic difficulty with erythema
multiforme
Investigation:
Not normally done
Rising antibody titre / presence of IgM antibodies
Viral culture or now mainly PCR

Question 18

Management of primary HSV

Answer 18

Acyclovir (200mg 5 x daily for 5 days) if found early or in immunocompromised
Fluids and soft diet
Analgesics / antipyretics (paracetamol)
Local antiseptics e.g. chlorhexidine Topical analgesics e.g. Difflam X-infection control

Question 19

Clinical features of 2ndary HSV

Management

Prophylaxis

Answer 19

Prodromal irritation
vesicles at or near mucocutaneous junction of lips
Crusting lesions 7-10 days
Usually reoccurs at the same sites

May occur intra-orally in nose or elsewhere

Acyclovir cream 5% if used OTC drying and antibacterial agentsvery early
Prophylactic:

rarely justified
prevents lesions in immunocompromised or those susceptible to erythema multiforme

Question 20

Value of Acyclovir in Herpes Labialis

Answer 20

Prophylactic - oral ACV (600-1000mg/day in 2 doses) is effective.
Reduces duration of pain by 1.4 days
Reduces time to lesion crusting by 2.1 days
Reduces occurrence of new lesions by at least
50%
Increases mean time to next recurrence from 46
to 118 days
Reduces mean number of recurrences over a 4 - month observation period

Question 21

Herpetic whitlow

Features

Answer 21

Herpetic infection of the fingers from handling the oral tissues of someone with active 1° or 2° Herpes simplex lesions (mainly dentists)
Very painful
Very difficult to treat Prevention better than cure - wear gloves

Question 22

HSV encephalitis

adults

neonates

Answer 22

70-80% mortality if untreated
only people >50s (HSV1) and neonates (HSV2) affected

Adults (HSV-1)
•Headache and behavioural changes over several days •Fever
•only 11% of cases have a history of recurrent HSV infections

Neonates (HSV-2)
•Skin rash, lesions and CNS symptoms
•Virus present in liver, lung and adrenal glands
•Respiratory distress
•Fits and convulsions
•Raised intracranial pressure
•Incidence is approximately one case per 300,000 live births in the UK

Question 23

HSV 2

Answer 23

Mainly genital

multiple vesicles rupture to form extensive sloughing ulcers

Question 24

HHV 3

1mary infection

reactivation

2ndary infection

Answer 24

varicella zoster
many similarities in structure and infection to HSV 1 and 2

chicken pox - varicella
- dominant in dorsal root/trigeminal ganglia

• age >50
• stress
• illness
• immunosuppression

herpes zoster - shingles

Question 25

Chicken pox - varicella

Answer 25

2ndary viraemia takes 10 days post infection

Question 26

Herpes zoster oral disease 3 phases

Answer 26

2ndary infection most commonly affects chest and back fluid filled rashes most commonly affects one division of the trigeminal N pre-herpetic neuralgia rash post herpetic neuralgia

Question 27

pre herpetic neuralgia

Answer 27

Pain in the distribution of the affected division of the trigeminal nerve Prior to the development of the rash May mimic dental pain

Question 28

rash (PHN)

Answer 28

``` Unilateral vesicles in the distribution of a branch of the trigeminal nerve Ophthalmic Maxillary Mandibular Vesicles break down to form Ulcers (mucosa) Crusting lesions (skin) Last 2-3 weeks ```

Question 29

Problems with zoster affecting ophthalmic region --

Answer 29

> glaucoma, cataract, double vision and corneal scarring

Question 30

Herpes zoster management new alternatives

Answer 30

Acyclovir 800mg 5 x daily for 7 days if seen soon after lesions develop Analgesics Ophthalmic referral if eye involved Avoid contact with children Valaciclovir 1g 3 x daily for 7 days Famciclovir 250mg 3 x daily for 7 days

Question 31

Post-herpetic neuralgia

Answer 31

10% of patients go on to get extremely unpleasant intractable burning pain in the distribution of the affected nerve More common in the elderly Effective early treatment of zoster may ↓ risk of neuralgia Treat pain with tricyclic anti-depressants and neuropathic pain drugs

Question 32

Epstein Barr virus Associated with Named after Anthony Epstein & Yvone Barr who discovered the virus in 1964

Answer 32

HHV4 Infectious Mononucleosis (Galndular Fever) – acute 1o infection with EBV Burkitt’s Lymphoma – a B-cell malignancy Nasopharyngeal Carcinoma – an epithelial cell malignancy Oral Hairy Leukoplakia – seen in AIDS patients and some transplant recipients

Question 33

Epstein Barr mechanism Why is latent infection needed?

Answer 33

Primary infection EBV replicates in ora-pharyngeal epithelial cells Becomes latent in B cells Virus persistence, subsequent replication in epithelial cells and release of infectious virus into saliva

Question 34

Infectious mononucleosis Oral manifestation

Answer 34

About 95% of the world’s population are infected with EBV Most infections are asymptomatic Symptoms include sore throat, swollen cervical lymph nodes and mild fever Infections in the western world are usually seen in young adults The disease can run a prolonged, episodic course, interfering with physical and scholastic performance (good excuse for poor exam results ) Petechiae on soft palate Creamy exudates on fauces Cervical lymphadenopathy

Question 35

Burkitt's lymphoma Prevalence Manifests Treatment

Answer 35

Malignant B cell lymphoma High prevalence in children in tropical africa <1500m where malaria is present Affects children sub clinically Usually affects jaw bone as tumour mass Nasopharyngeal carcinoma Severe, clinical EBV infections early in childhood predispose to Burkitt’s Lymphoma – EBV immortalises B cells Treatment – cyclophosphamide (chemo

Question 36

HHV 5 Rarely causes Immunocompromised/AIDS

Answer 36

Cytomegalovirus Glandular fever like illness Salivary gland swelling Large ragged oral mucosal ulcers Salivary gland swelling Retinitis

Question 37

HSV 8 in AIDS

Answer 37

Kaposi's sarcoma