PBL 1 Flashcards
Which virus causes chickenpox and shingles?
Varicella-Zoster virus
what type of virus is varicella zoster virus?
a strain of herpes virus
dsDNA enveloped virus
how does the varicella zoster virus enter host cells?
it fuses its membrane with the host cell membrane and releases its capsid inside the cell
capsid binds to nucleus and injects the viral DNA inside where they are transcribed into RNA and then translated into capsid proteins at the ribosome
capsid and viral DNA fuse together in the Golgi complex to form the lipid membrane
newly formed viruses leave the cell
how is the varicella zoster virus transmitted?
respiration- sneezing and coughing
direct contact with oral or skin lesions
outline primary viremia of varicella?
virus comes into contact with respiratory mucosa or skin of person and replicates in the epithelial cells. 4-6 days after infection the virus infects reticuloendothelial cells in the liver and spleen
outline secondary viremia of varicella?
2 weeks after primary viremia the virus infects immune cells (particularly T cells). infected T cells express proteins which bind to skin cell receptors which allows the release of the virus. the virus then infects keratinocytes,
what are Tzanck cells?
when infected keratinocytes fuse together to form multi-nucleated cells
what causes the small initial lesions on the skin in varicella?
uninfected cells secrete interferons to attempt to inhibit viral protein synthesis - this causes the lesions
outline the pathophysiology of shingles (herpes zoster)?
virus infects sensory neurone in the skin during varicella and they travel retrogradely to the ganglia
when the immune system kicks in to remove varicella, most of the viruses in the body are eliminated but those in the ganglia are spared
these viruses can remain dormant for Many years until the immune system weakens and the virus can be reactivated, travel up the neurone and infect the innervated dermatome
what are symptoms of varicella?
fever, headache, weakness, rash and spots, painful sores on mucosal surfaces
describe how the rash in varicella changes over time?
1-3 weeks after exposure, flat/red/itchy lesions (macule) form, overtime these become elevated (papules) and eventually they become small-fluid-filled vesicles
when do scabs form over vesicles in varicella?
1-2 days after appearance
how often do new crops of lesions appear in varicella?
every 3-5 days
what are macules?
a flat, distinct, discolored area of skin less than 1 cm wide
what are papules?
a raised area of skin tissue that’s less than 1 centimeter around.
when is varicella infectious from and to?
2 days before the spots appear to until they crust over
what are the symptoms of shingles?
unilateral rash that causes pain, itching and tingling that can last up to 4 weeks
how long can pain last for in the affected dermatome in shingles?
why?
90 days (postherpatic neuralgia) nerve fibres are damaged so messages between skin and brain get confused = chronic pain
can you catch chickenpox from someone with shingles?
yes. usually only if you haven’t had it before
can you catch shingles from someone with chickenpox?
no
can you catch shingles from someone with shingles?
no
what are some common complications of varicella zoster?
bacterial infections of the skin septicaemia TSS necrotising fasciitis osteomyelitis septic arthritis
how can you diagnose the varicella zoster virus?
skin lesion appearance
Tzanck test to look for multinucleate giant cells in the fluid of vesicles
blood test for varicella antibodies
PCR to look for viral DNA
how do you treat varicella zoster?
topical antipruritic meds analgesics anti-inflammatory meds antivirals varicella zoster immunoglobulin varicella vaccine zoster vaccine
why shouldnt you task aspirin when you have varicella?
use of aspirin with varicella has been associated with Reye’s syndrome (toxic build up of ammonia and swelling of liver and brain)
what are antivirals?
a class of medication used for the treatment of viral infections
what antivirals do we use to treat influenza?
M2 ion channel inhibitors, neuraminidase inhibitors, endonuclease inhibitors
how do M2 ion channel inhibitors work?
they block the viruses entry into the cell
what do endonuclease inhibitors do?
blocks the transcription of mRNA
what do neuraminidase inhibitors do?
stop the release of viruses from the infected host cells
which types of drugs do we use to treat HIV?
entry inhibitors, reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrate inhibitors, protease inhibitors
how do non-nucleoside reverse transcriptase inhibitors work?
block HIV reverse transcriptase which is used to convert its RNA into DNA = prevents replication
which antivirals do we use to treat hepatitis?
nucleoside and nucleotide analogues, NS3/4A protease inhibitors, NS5A inhibitors and NS5B polymerase inhibitors
how do nucleoside and nucleotide analogues work to treat hepatitis?
by inhibition of HBV polymerase activity resulting in decrease of viral replication.
which drugs do we use to treat herpes?
acyclovir, ganciclovir and penciclovir
how does aciclovir work?
It’s converted to acyclovir triphosphate, which competitively inhibits viral DNA polymerase
how does ganciclovir work?
its triphosphate form inhibits viral DNA polymerase
how does penciclovir work?
its triphosphate form inhibits viral DNA polymerase
why do most people not require antiviral drugs?
as they will have a mild illness and will recover quickly so the risks of side effects may outweigh the benefit
who are the candidates for antivirals?
those over 65, have chronic disease, anyone under 4 and anyone with a compromised immune system
what are some common side effects of antivirals?
nausea and vomiting, diarrhoea and stomach ache, headache
why are antivirals tricky to develop?
because viruses are so small and mutate quickly
viruses are also within host cells so its hard not to damage the host
