Human Herpesviruses Flashcards
Structure and classification of Herpesviruses What disease are caused by Herpesviruses How Herpesviruses infect human cells Pathobiology of Herpes simplex virus and other Herpesviruses
Herpeton
- greek for creep
Icosahedral capsid surrounding ds DNA
Virus size 120-200 nm
80 genes coding for 100 proteins
beta herpes
slow growth in t cells and leukocytes
cytomegalovirus
human herpesvirus 6
human herpesvirus 7
gamma herpes virus
epstein barr
human herpesvirus 8
herpes simplex virus 1+2
oropharyngeal and genital herpes
varicella zoster
chicken pox / shingles
epstein barr virus
infectious mononucleosis, burkitt’s lymphoma, nasopharyngeal carcinoma
cytomegalovirus
Cytomegalic inclusion disease in utero (newborns and immunocompromised)
HHV 6
Exanthem Subitum (6th disease)?
HHV-7 HHV-8
Fatigue syndrome
HHV 7
Pityriasis rosea?
HHV 8
Kaposi’s Sarcoma (in AIDS patients)
Infection and replication
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
HSV1
Process
Symptoms
Reactivation
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
HSV 2
Cause
Mainly genital infections
Natural history of HSV infections
source of virus -
symptoms
Primary infection
Skin lesions
Saliva
genital lesions
genital secretions
90-99% asymptomatic
1-10% symptomatic
primary HSV
Very common
Mainly affects young children and young adults
primary HSV
Very common
Mainly affects young children and young adults
Herpetic gingivostomatitis
Clinical features
diagnosis
investigation
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
Management of primary HSV
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
Clinical features of 2ndary HSV
Management
Prophylaxis
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
Value of Acyclovir in Herpes Labialis
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
Herpetic whitlow
Features
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
HSV encephalitis
adults
neonates
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
HSV 2
Mainly genital
multiple vesicles rupture to form extensive sloughing ulcers
HHV 3
1mary infection
reactivation
2ndary infection
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
Chicken pox - varicella
2ndary viraemia takes 10 days post infection
Herpes zoster
oral disease
3 phases
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
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
rash (PHN)
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
Problems with zoster affecting ophthalmic region –
> glaucoma, cataract, double vision and corneal scarring
Herpes zoster management
new alternatives
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
Post-herpetic neuralgia
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
Epstein Barr virus
Associated with
Named after Anthony Epstein & Yvone Barr who discovered the virus in 1964
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
Epstein Barr mechanism
Why is latent infection needed?
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
Infectious mononucleosis
Oral manifestation
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
Burkitt’s lymphoma
Prevalence
Manifests
Treatment
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
HHV 5
Rarely causes
Immunocompromised/AIDS
Cytomegalovirus
Glandular fever like illness
Salivary gland swelling
Large ragged oral mucosal ulcers
Salivary gland swelling
Retinitis
HSV 8 in AIDS
Kaposi’s sarcoma
