Viro Flashcards
Outline the activation and mechanism of action of acyclovir (3)
Acyclovir per se inactive. Mono- and bi-phosphorylated by viral thymidine kinase, and tri-phosphorylated by cellular enzyme. Incomplete sugar ring chain termination when incorporated into DNA by DNA polymerase.
Outline the pathogenesis of neonatal herpes simplex infection (2)
Maternal genital infection peri-partum, often primary, may be reactivation (therefore prevention = caesarean section if genital herpes is known); virus infects neonate, vesicles may be present, generalised infection (multi-organ), high case fatality rate.
Outline four (4) medically relevant features of human herpesviruses infections (4x1 = 4)
Enveloped viruses
Lifelong infections by establishing latency
Periodic shedding in body fluids facilitates human to human transmission
Prevalence of infection is very high
Morbidity associated with most infections is low (infections are often asymptomatic)
Disease may be due to primary infection or reactivation
List three (3) life-threatening diseases caused by herpes simplex virus infections (3x½ = 1
Neonatal herpes, Herpes encephalitis, Herpes hepatitis, Herpes pneumonia, Disseminated herpes simplex
Describe three (3) severe, often fatal complications of herpes simplex virus infection (6)
- Encephalitis. HSV1 more severe than HSV2. 2/3 of cases are reactivation. Affinity for temporal lobes. High mortality. Urgent treatment before testing.
- Neonatal herpes. Infected via maternal genital herpes, often primary, also reactivation. Severe systemic disease. Vesicles often only subtle.
- Disseminated herpes. Causes hepatitis, liver failure (often rapidly progressive and fatal), ARDS, multi-organ failure.
State two (2) conditions that herpes simplex can cause in the eye (1)
Conjunctivitis, keratitis, dendritic ulcer
List three (3) malignancies caused by herpesviruses, name the virus causing each malignancy, and name one risk factor associated with each malignancy (9x½ = 4½) (NB)
Kaposi’s sarcoma HHV8 Immunodeficiency
Primary effusion lymphoma HV8 Immunodeficiency
Burkitt’s lymphoma EBV Malaria, Living in Central Africa
Outline three (3) complications of primary varicella infection in non-pregnant adults (8)
Secondary bacterial skin infections Pneumonia; interstitial pneumonitis Post-infectious encephalomyelitis; aka ADEM Meningoencephalitis Stroke Haemorrhagic varicella Shingles
State the primary means of diagnosing a case of shingles (1)
Clinical diagnosis
Name five (5) complications of varicella infection (2½)
Secondary skin infection, scarring, stroke, post-infectious encephalomyelitis, pneumonia, haemorrhagic varicella, congenital infection, hepatitis, etc
State where the varicella-zoster virus becomes latent (1)
Dorsal root ganglia
State three (3) clinical scenarios when one should consider giving post-exposure prophylaxis after varicella-zoster virus exposure (3)
Pregnancy, neonate, immunodeficiency
Outline the pathogenesis of this condition (5) (NB) (Shingles)
Following primary varicella infection (chicken pox), usually in childhood, the virus establishes latency in sensory nerve ganglia that supply the skin. The genome persists in these cells, but no viral replication takes place. The virus may reactivate from this state of latency if the host becomes immuno-suppressed - this usually only happens many years later. Cycles of virus replication occur in the sensory ganglia and virus particles travel down the axons to re-infect the skin supplied by the affected ganglion. Re-infection of skin manifests as a blistering rash.
Outline who would be at risk of acquiring this infection from Mr Kruger (1) (shingles)
Contacts who have not had chicken pox/ not immune to varicella.
Name four (4) interventions that can be used to protect contacts from contracting this virus (2)
Acyclovir, zoster hyper-immune globulin, varicella vaccine, avoid exposure
Name a drug that can be used to treat this condition (½) (VZV)
Aciclovir
State the class of antiviral agents to which this drug belongs (½)
Nucleoside analogue
How does it interfere with virus replication? (2) (NB)
Chain termination during DNA synthesis, nucleotide analogue, incorporated into DNA by DNA polymerase
Outline why this drug only acts in cells infected with herpesviruses (1)
It requires a viral enzyme, thymidine kinase, to be activated.
Name the mode of transmission for EBV (1)
Close contact/saliva
Briefly outline the signs/ symptoms of primary Epstein-Barr virus infections in young adults (4x½ = 2) (NB)
Fever & malaise, rash, lymphadenopathy, sore throat, Hepato-splenomegaly, atypical lymphocytosis
Name the commonest clinical syndrome associated with EBV infection (1)
Infectious mononucleosis (glandular fever)
Name four (4) other conditions associated with EBV infection (2)
Note, we are looking for causal associations. Any 4 of:
Burkitt’s lymphoma, Hodgkin’s disease, Oral hairy leukoplakia, Naso-pharyngeal carcinoma, Non-Hodgkin’s lymphomas in immunocompromised patients, Polyclonal lymphoproliferative disorders (post-transplant lymphoproliferative disease), X-linked lymphoproliferative disorder, Leiomyosarcomas
Name the cell type in which EBV establishes long term latency (1)
B lymphocyte
Explain how EBV establishes long term persistence in these cells (2)
EBV expresses a set of latency genes that transform the B cell. These genes induce the B cell to recapitulate the events that are triggered after antigen stimulation.
Name one non-haematological cancer that can be caused by EBV (½)
NPC, gastric adenoca
Outline the clinical information provided by the following EBV serological tests.
Paul-Bunnell/Monospot (2)
EBV nuclear antigen IgG (2)
EBV viral capsid antigen IgM (2)
a) Paul-Bunnell/Monospot (2) Detect heterophile Ab which is present during acute infection. Screening for 1o EBV infection.
b) EBV nuclear antigen IgG (2) Detect post convalescent antibody so if positive can be used to exclude primary infection.
c) EBV viral capsid antigen IgM (2) Detectable during acute infection so can be used as confirmation test.
Name in full the most common herpes virus that can be transmitted to the foetus pre-natally (1)
Cytomegalovirus
Describe two (2) methods to confirm the diagnosis of this congenital infection (6 x ½ = 3)
Direct: detection of virus in urine/amniotic fluid through culture or PCR in the first 3 weeks of life
Indirect: detection of CMV IgM in foetal cord blood/newborn blood in the first 3 weeks of life
If the students don’t get the direct and indirect methods, they must at least explain the PCR and serology adequately.
Describe varicella infection in pregnancy in both the mother and the foetus/ neonate (6)
<20 weeks
Foetus – Usually low risk of congenital abnormalities, limb damage/ hypoplasia, skin damage, microphthalmia
Mother – Typical adult varicella with vesicular rash with usual distribution and itch and pulmonary infection
> 20 weeks
Foetus – Minimal risk to foetus (i.e. much less than age <20 weeks gestation)
Much higher risk to mother (complications); neonate – severe risk, urgent acyclovir prophylaxis needed
