Virology - Herpesviruses Flashcards
1
Q
Define latent infection.
A
Latency reflects persistent infection during which no infectious virus is produced, except during intermittent periods of reactivation.
2
Q
Define reactivation.
A
Reactivation from the latent state may be restricted to asymptomatic virus shedding or manifest as clinical disease.
3
Q
Define recurrence.
A
This term is used when reactivated virus produces clinically apparent disease.
4
Q
What are the three subdivisions of the herpesviridae family?
A
- alpha: simplexvirus and varicellovirus genera
- beta: cytomegalovirus and roseolovirus genera
- gamma: lymphocryptovirus and rhadinovirus genera
5
Q
List the human herpesviruses, both vernacular and approved names.
A
6
Q
Outline herpesviruses.
A
- Structure: Icosahedral protein capsid (~100 nm) containing 162 capsomeres, containing a DNA genome. Outside the capsid is a proteinaceous layer, the tegument, surrounded by lipid envelope containing spikes of viral glycoproteins. Whole particle ~200 nm diameter.
- Genome: linear dsDNA that varies in length and composition. Genes coding for viral glycoproteins, major capsid proteins, DNA replication enzymes, some latency transcripts.
- Some herpesviruses are predominantly:
- neurotropic (HSV and VZV)
- lymphotropic (EBV, HHV 6 and 7)
7
Q
Outline the characteristics of the three herpes subfamilies.
A
- alphaherpesvirinae: rapid growth in cultured cells, latency in sensory ganglia
- betaherpesvirinae: slow growth in cultured cells, restricted host range
- gammaherpesvirinae: growth in lymphoid cells
8
Q
Outline how herpesviruses replicate. [7]
A
- Binding of viral receptor-binding proteins to cell surface proteoglycans
- Envelope fuses with cell membrane
- Nucleocapsids cross the cytoplasm to the nuclear membrane
- Replication of viral DNA and assembly of capsids in the nucleus
- The tegument takes part in the activation of genes; immediate early (IE), early (E), and late (L) genes.
- The genome is thought to be replicated in a ‘rolling circle’ manner. It is inserted into capsids in the nucleus
- Viral glycoproteins are processed in the Golgi apparatus and are incorporated into the host cell membrane, from which the viral envelope is acquired
9
Q
Outline the pathogenesis of herpes simplex virus.
A
- There are two distinct types of of HSV: type 1 and 2
- Type 1 strains are associated primarily with the mouth, eye, and nervous system, and type 2 strains with the genital tract
- The typical lesion produced by HSV is the vesicle: ballooning degeneration of intra-epithelial cells, which contains infectious fluid. Base of vesicle contains multinucleate (Tzanck) cells and infected nuclei contain eosinophilic inclusion bodies. When this breaks down an ulcer forms, crusts over, then heals.
- NK cells recognise and destroy HSV-infected cells, and herpesvirus glycoproteins are recognised by the immune system and cytotoxic (CD4+, CD8+) and helper (CD4+) T lymphocytes which activate B lymphocytes to produce antobodies.
- During replication the viral particles enter the sensory nerve endings and are transported up the axon to the nerve body in the sensory dorsal root ganglion by retrogade axonal flow. Replication in neurons end in lytic infection and neuronal cell death. Some establish latent infection.
- Factors influencing reactivation include UV light, fever, trauma, stress.
10
Q
Outline the different sites of infection for HSV.
A
- Oral infection
-
Skin infection
- Herpetic whitlow (fingers)
- Eczema herpeticum
- Eye infection
- CNS infctions
- HSV encephalitis (rare)
- HSV meningitis
- Genital tract
- Neonatal herpes (rare)
11
Q
Outline the diagnosis of HSV.
A
- Scrapings or swabs taken
- Detection of viral DNA by PCR most sensitive and specific method
- Complement fixation tests (CFTs) useful in diagnosing primary infections, although no longer widely available in the UK.
- Encephalitis can be detected by testing CSF
- Virus isolation for immunofluorescence staining and electron microscopy
12
Q
How is HSV treated?
A
Aciclovir, inhibits viral DNA synthesis. Can be oral, topical, or IV.
13
Q
What are the two forms of infection of Varicella-zoster virus (VZV)?
A
- Primary infection: varicella (chickenpox) is a generalised eruption
- Reactivated infection: zoster (shingles) is localised to one, or a few, dermatomes
14
Q
Outline VZV.
A
- Varicella and zoster are identical. The virus has the morphology of all herpesviruses.
- Following attachment to the cell surface glycosaminoglycans and fusion, the nucleocapsid enters the cells and viral DNA is released into the nucleus where virus replication takes place.
15
Q
Outline the pathogenesis of varicella and zoster.
A
- Varicella: predominantly affects children. Virus enters through URT or conjunctivae, and may multiply in local lymph tissue before before entering the blood. After replicating in reticulo-endothelial sites, a second viraemic stage occurs with the appearance of skin and mucosal lesions. VZV vesicles lie in the middle of the epidermis, pustules dry up, scab, and desquamate.
- Zoster: latent virus is found in neurons and satellite cells in sensory ganglia, similar to HSV. Reactivation can happen at any age, stimulus is unknown. Ususally limited to one dermatome; in adults this is usually thoracic or in the upper lumbar regions.
19
Q
Outline Epstein-Barr virus (EBV).
A
- EBV is often acquired in childhood when it is generally asymptomatic
- Gives rise to infectious mononucleosis (glandular fever) in up to a quarter of individuals when infection is delayed until adolescence
- The B lymphocyte is the principal and essential cell infected
- Two types of EBV, type 1 and type 2, however they are very similar
21
Q
Outline the clinical manifestations of EBV and other complications.
A
- Infectious mononucleosis is seen in the 15-25 years age group when primary EBV infection is delayed. Incubation period is 30-50 days, and the onset is abrupt with sore throat, lymph node enlargement, and fever, often accompanied by malaise, headache and sweating. Pharyngitis may be severe, accompanied by a greyish-white membrane and gross tonsillar enlargement. Splenic enlargement in severe cases.
- African Burkitt’s lymphoma (endemic)
- Nasopharyngeal carcinoma (South-East Asia and China)
- Hodgkin’s lymphoma
-
T/NK cell lymphoma
*
22
Q
Outline how EBV is diagnosed.
A
- Infectious mononucleosis is accompanied by the production of heterphil agglutins that can be detected by a rapid slide agglutination test (Paul-Burnell test)
- Immunostaining using ELISA detecting IgM EBV antibody (monoclonal antibody)
- Raised leukocyte count and 20% have atypical appearance (bulky cytoplasm, irregular nuclei)
24
Q
Outline cytomegalovirus (CMV).
A
- Nuclei of infected cells contain large inclusion bodies resembling ‘owl eyes’, as can be seen with an IHC stain under the light microscope.
- CMV has the same general herpesvirus structure and replicates in the salivary glands, kidney, respiratory tract, and other epithelial sites.
- Obvious growth cycle in culture, grows a lot slower compared to HSV.
- Transmissable to foetus via placenta, and neonates via breast milk
25
Q
Outline the pathogenesis of CMV.
A
- Primary infection with CMV may be acquired at any time persists in the host for life. Reactivation is common, and virus is shed in body secretions such as urine, saliva, semen, breast milk and cervical fluid.
- In young adults it is transmitted through kissing and sexual contact, and can lead to infectious mononucleosis, splenomegaly, and impaired liver function.
27
Q
How is CMV diagnosed?
A
- Conventional culture is used to isolte the virus, but this approach has been replaced by genome detection assays
- CMV must be determined in the urine or salive in the first three weeks of life to demonstrate congenital infection
- Need to show CMV is in affected tissue, either through IHC or genome detection assays
- ELISA for CMV Ig
