NNRTIs Mechanism of Action and Pharmacokinetics

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What is the purpose of using protease inhibitors in antiretroviral therapy?

To generate synthetic substrates for reverse transcriptase

To target multiple stages of the HIV life cycle (correct)

To induce a conformational change in the enzyme structure

To competitively inhibit the incorporation of native nucleotides

What is the mechanism of action of Nucleos(t)ide Reverse Transcriptase Inhibitors (NRTIs)?

By lacking a 3′hydroxyl group to terminate DNA elongation

By inducing a conformational change in the enzyme structure

By competitively inhibiting the incorporation of native nucleotides (correct)

By blocking replication of the viral genome by phosphorylation

How do NNRTIs act as inhibitors in HIV treatment?

By binding to the active site to block enzyme function

By inducing a conformational change in the enzyme structure (correct)

By phosphorylation to generate synthetic substrates

By competitively inhibiting reverse transcriptase activity

Why are Nucleos(t)ide Reverse Transcriptase Inhibitors important in HIV pharmacokinetics?

To enter cells and be phosphorylated for substrate generation Signup and view all the answers

How do Nucleos(t)ide Reverse Transcriptase Inhibitors (NRTIs) exert their pharmacodynamic effect?

Competitive inhibition of reverse transcriptase enzymes Signup and view all the answers

Which enzyme do Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) act on?

Reverse transcriptase Signup and view all the answers

Why do NRTIs require intra-cytoplasmic activation via phosphorylation by cellular enzymes?

To be converted into their active triphosphorylated form Signup and view all the answers

What is the mechanism of action of NNRTIs?

Noncompetitive inhibition Signup and view all the answers

What is the selective toxicity of NRTIs based on?

Affinity for DNA-polymerase gamma (mitochondrial enzyme) Signup and view all the answers

What adverse effect is commonly associated with Efavirenz use?

Abnormal dreams Signup and view all the answers

Which Nucleos(t)ide Reverse Transcriptase Inhibitor (NRTI) does not require triphosphorylation for activation?

Tenofovir Signup and view all the answers

Which HIV strain are Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) active against?

HIV-1 only Signup and view all the answers

What is a common characteristic of Protease Inhibitors (PIs)?

Associated with lipodystrophy syndrome Signup and view all the answers

What is significant about the resistance development with Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)?

Rapid resistance (days or weeks) if given as monotherapy Signup and view all the answers

Where is the HBZ gene encoded in relation to the DNA strand?

Complementary negative sense strand Signup and view all the answers

What is the characteristic of HBZ expression during infection?

Continuously expressed throughout the infection Signup and view all the answers

In ATL cells, what effects does Tax-independent cell proliferation lead to?

Recapitulation of the effects of Tax protein Signup and view all the answers

Which cellular transcription factors are constitutively expressed in aggressive ATL cells?

NF-κB, NF-AT, AP-1, STAT-5 Signup and view all the answers

What is a genetic predisposition to Adult T-cell Leukemia (ATL) according to the text?

Certain human leukocyte antigen (HLA) alleles Signup and view all the answers

Which feature is characteristic of Adult T-cell Leukemia (ATL) at an advanced stage?

Presence of systemic lymphadenopathy Signup and view all the answers

How is HTLV-1 infection diagnosed according to the text?

Demonstration of antibodies to HTLV-1 in the patient's serum Signup and view all the answers

What is a cellular effect caused by the Tax protein of HTLV-1?

Induction of cell cycle progression Signup and view all the answers

How does the HTLV-1 protein p12I contribute to down-modulation of MHC-I-restricted antigen presentation?

By sequestering MHC-I alpha chain in the endoplasmic reticulum (ER) Signup and view all the answers

What is one of the effects of Tax-dependent cell proliferation of escape mutants?

Low-grade Acute T-cell Leukemia (ATL) Signup and view all the answers

How does HBZ contribute to leukemogenesis in HTLV-1 infection?

Suppressing Tax-mediated proviral transcription Signup and view all the answers

What characterizes the stage of low-grade ATL in HTLV-1 infection?

Presence of skin lesions, lymphadenopathy, and hepatosplenomegaly Signup and view all the answers