Hemaptopoietic VIruses Flashcards by Emily Prazak

What is the general mechanism of most current antiviral drugs?

they inhibit viral genome replication by mimicing the shape of a nucleotide (or nucleoside) and plugging up the enzymes that replicate the viral genome.

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What nucleoside does acyclovir mimic?

guanosine

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What must happen to acyclovir for it to be active?

it has to be phosphorylated by viral thymidine kinase

after that, host kinases will continue the process until it can be incorporated

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Why does acyclovir only work on cells that are actively proliferating?

Because expression of thymidine kinase only occurs when the cells enter S phase

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What does viral pathogenesis involve in the acute phase? In the long term?

acute: cell death and inflammation

long term: malignancies and immune suppression (with opportunistic infections)

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How can viruses cause cancer (in general terms)?

they express viral oncogenes that mimic and interact with the host cell’s normal replication machinery and promote uncontrolled cellular proliferation

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What are the three stages viral oncogenes can act at?

the G1-S phase checkpoint
The regulation of cell death by apoptosis
the immunological synapse

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Activation of what molecule is the first step in progression to S phase?

Cyclin D/CDK4

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What signalling pathway controls the cell’s normal apoptotic machinery?

In the mitohcondrial membrane, when Bid makes a complex with Bax, it forms a pore that allows cytochrome C release to the cytoplasm where it activates caspases and causes apoptotic cell death

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Which complex opposes the Bid/Bax complex and inhibits cytochrome C release (antiapoptotic)?

Bcl2/Bid

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What is the genomic organization of parvovirus

linear ssDNA (group 2)

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Does parvovirus have an envelope?

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What is the capsid symmetry of parvovirus

icosahedral

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What is the tropism for parvovirus?

erythroid progenitor cells

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How does parvovirus establish infection in the host cell?

recognizes a p antgien (globoside) on progenitor cells
binds to it
internalized through coated pits

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How does parvovirus replicate

enters nucleus and forms a hairpin structure which is a self primer for DNA replication

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The relationship between the viral protein NS1 and pathogenesis is….

NS1 is a cytotoxic molecule and causes hemolysis of the RBC

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A typical clinical presentation of erythema infectiosum is…

fifth’s disease: fever, slapped cheek and lacy rash on extremities

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What is the treatment for parvovirus?

There is no effective antiviral, so supportive

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Transient aplastic crisis can occur when…

If a person already has a baseline blood disorder and they get parvovirus - they pretty much get a total lack of RBCs

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Other conditions caused by parvovirus are…

hydrops faetalis: birth defect causing eye disformity

or chronic anemia in immunosuppressed patients

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How is parvovivur diagnosed? aka…what do you do assays for?

immunofluoescence antibody assay - there are three things you can test for: b19 DNA (the earliest detection) or b19 IgM (the usually test - but remains detectable for 3 months after infection), or PCR (detected for years after infection)

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Colorado tick fever: genomic organization

segmented dsDNA

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Colorado tick fever: enveloped?

naked

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Colorado tick fever: capsid symmetry

icosahedral

colorado tick fever: tropism?

erythroblasts

Animal vector for colorado tick fever?

rocky mountain wood tick

Geography and season for colorado tick fever?

high altitudes | march - november (summer basically)

What is the clinical presentation of colorado tick fever?

biphasic fever, myalgia, light sensitivity, rash is uncommon, also uncommon is hemorrhagic disease, meningioencephalitis

What is the substrate of the Dicer/RISC complex for colorado tick fever

dsRNA is cleaved by dicer and then RISC is the thing that binds the complementary ssRNA, which will go to the complementary mRNA to break it down and halt translation

How does CTFV protect its genome from DICER/RISC

RNA replication occurs in cytoplasmatic viral factories - protects it from the complex

CTFV uses the ___ stand of its genome for transcription and as a template for replication of the ___strand.

+RNA of the -RNA strand

CTFV diagnosis?

immunofluorescent antibody test for CTFV IgMs plus CBC with leukocytopenia and thrombocytopenia

CTFV treatment?

supportive - no effective antiviral

Associated conditions for CTFV?

Rocky mountain fever - very similar clinical presentation (but it's bacterial)

CMV genomic organization

linear ssDNA

CMV envelope?

yes

CMV capsid symmetric?

icosahedral

CMV tropism? systemic? latent?

epithelial cells as systemic infection (lytic) Latent in lineage-commited myeloid cells

How does CMV get into the host cell and replicate?

viral gycoproteins bind receptor on host cell and enter by endocytosis

How does CMV evade host immune response?

uses nuclear viral factories and the virus buds out through golgi bodies - so it's never in contact with cytoplasm

A typical presentation of CMS infections mononucleosis...

same presentation as mono: fever, sore throat, lymphadenopathy, lymphocytosis

What's the diagnosis for CMS

enzyme linked immuno assay - for protein pp65 found in neutrophils that are infected plus the present of owl eye's cells in blood smear

What are the associated conditionsf or CMV?

microcephaly with fetal infections CMV retinitis hepatosplenomegaly and jaundice and meningioencephalitis

What's the treatment for uncomplicated CMV infection?

supportive

WHat's the treatment for severe systemic CMV infections?

ganciclovir

Why is acyclovir not effective against CMV?

CMV doesn't have thymidine kinase

Human Herpes VIrus - genomic organization?

linear dsDNA

HHV envelope?

yes

HHV capsid symmetry?

icosahedral

HHV tropism?

CD4 T cells

How do HHV 6 and HHV7 differ?

6 - T cells, B cells, and NK -d detected in low levels of saliva 7 - mostly just T lymphocytes, high detection in saliva

WHat does HHV 6 use to enter host cell?

CD46

How does HHV 7 enter the cell?

binds to CD4

Most cases of exanthem subitum (roseola) occur in children of what age?

under 2

What are the symptoms of exanthem subitum?

nonpuritic morbiliform rash, usually on the trunk - always develops after a high fever (this is the happy rash kid)

Treatment for HHV6 or 7?

supportive - acet and ibu for fever

WHat happens in adults?

IT's more of a mono-like illness.

What can the reactivated infection cause/

encephalitis

In immunocompromised patients, what can happen?

enephalitis, plus all the other normal symptoms

Treatment for severe HHV if encephaitis?

ganciclovir, foscarnet, and cytoforvir

Genomic orgnization of kaposi?

circular dsDNA

Kaposi envelopes? capsid?

yes - icosahedral

What are the malignancies associated with KSV?

Kaposi sarcoma Primary effusion lymphoma Multicentric Castleman's disease

Who are affected by KSV?

People with immune compromise; especially HIV subsaharan africa, 50% of people are infected

KSV tropism?

B cells

What is vFLIP a homologue of? What does it do?

FLICE (which normally regulate apoptosis by inhibiting it)....so it inhibits apoptosis ,thus causing cancer

What is KSV's vBcl-2 a homolog of? What does it do?

Bcl-2 of the host cell (duh) so it also inhibits apoptosis

KSV vGPCR is a homolog of what?

IL6 - which will increase B cell proliferation

KSV's vCyclin is a homolog of what? what does it do?

host cyclin so it will go thorugh the G1-S checkpoint and continue proliferating

What's the treatment for KSV?

Ganciclovir, Cidofir and Foscarnet (just like HHV)

What is ganciclovir?

synthetic analog of 2' deoxy guanosine that acts as a chain terminator in virally infected cell

What is cidofir?

a monophosphate nucleotide analog - acts as a competitive inhibitor of DNA polymerase to terminate chain

What is foscarnet?

binds to pyrophosphate analog that binding site of DNA polymerases - don't affect human DNA polymerase at the levels given

What is the genomic organization of human T cell lymphotrophic virus

ssRNA+

Is HTLV enveloped? capsid?

yes - icosahedral

What is the tropism for HTLV? How are HTLV1 and 2 different in this regard?

T cells: HTLV1 does CD4 and HTLV2 does CD8

In what population is HTLV2 most common?

american indians and injection drug users

How does HTLV enter the host cell?

It binds to GLUT-1 on the T cells

How does HTLV become a provirus?

After it enters the host cells, the capsid uncoats and the virally encoded reverse transcriptase creates a DNA copy that is then integrated into the host genome under the influence of viral integrase

What does the transcription factor Tax doe for HTLV?

It upregulates expression of IL-2 and the IL-2 receptor, which induces proliferation of T cells (also protooncogenes c-fas, c-erg and then GM-CSF)

What cancer is associated with HTLV?

acute T-cell lymphoma (ATL)

What is the typical presentation of ATL?

lymphadenopathy, hypercalcemia, lytic bone lesions and cutaneous skin involvement: ranges from papules, nodules, plaques, pathces, and diffuse erythroderma

What is HTLV Associated Myelopathy (HAM)

It's a chronic progressive demyelinating disease caused by auto-reactivity

What is the typical presentation of HAM?

4th decade of life...sublte onset of progressively stiff gait, gradually progressing to weakness, spasticity, back pain, urinary incontinence, apresthesias, hyperreflexia, clonus, babinski, etc.

Hemaptopoietic VIruses Flashcards

(85 cards)