Section A (Viruses) Practice exam questions Flashcards
Discuss the role of RNA interference (RNAi) in antiviral defence and explain how viruses have evolved to counteract this mechanism. Evaluate whether RNAi could be harnessed for antiviral therapeutics.
Describe the RNAi machinery, including DICER, Argonaute, and the RISC complex.
Explain how plant and insect viruses are suppressed via RNAi.
Provide examples of viral suppressors of RNAi (e.g., VSRs) and their mechanisms.
Discuss current challenges and prospects in developing RNAi-based antiviral therapies.
Explain the stepwise process of genome delivery to the nucleus by DNA viruses such as adenoviruses, and evaluate how this process has informed viral vector design.
Outline the entry, trafficking, and uncoating steps required for nuclear delivery.
Discuss how adenoviruses use cellular motor proteins and the nuclear pore complex.
Examine modifications made to adenoviruses for gene therapy and vaccination purposes.
Consider risks such as replication-competent virus emergence and immune responses.
Evaluate how structural biology has contributed to the design of next-generation vaccines against enveloped viruses. Use RSV and HIV-1 as case studies.
Describe structural vaccinology principles and methods (e.g., cryo-EM, structure-guided design).
Explain how prefusion stabilization of viral proteins enhances immunogenicity.
Compare the design of neutralizing antibodies and vaccine immunogens.
Assess remaining challenges, such as antigenic variability and eliciting durable responses.
Describe the various membrane fusion strategies used by enveloped viruses and analyse how these strategies influence viral tropism and immune evasion.
Compare class I, II, and III viral fusion proteins and their triggers.
Explain pH-dependent vs pH-independent fusion entry mechanisms.
Discuss how structural rearrangements facilitate fusion.
Relate fusion mechanisms to host cell specificity and antibody escape.
Examine how positive-sense RNA viruses manipulate host cell membranes and resources to form viral replication complexes. Why is this understanding critical for antiviral development?
Outline the morphological changes induced by replication complex formation.
Highlight viral and host factors involved (e.g., viral proteases, lipid synthesis).
Provide examples of replication structures in viruses like Dengue or Poliovirus.
Discuss implications for targeting replication machinery in antiviral therapy.
Analyse how enveloped viruses hijack the host endosomal system during entry and discuss the role of pH and proteases in viral fusion.
Describe how viruses exploit endocytosis and endosomal maturation.
Explain the importance of low pH and host proteases (e.g., cathepsins, furin).
Use examples like Influenza, Ebola, or SARS-CoV-2.
Discuss therapeutic implications of blocking endosomal pathways.
Explain the structural and functional differences between the major classes of viral fusion proteins and how these differences impact vaccine design.
Define Class I, II, and III fusion proteins and their structural features.
Describe the conformational changes upon activation.
Link structure to immunogenicity and neutralizing antibody binding.
Discuss implications for pre-fusion stabilization strategies in vaccine design.
Discuss the key features of adenoviral vectors that make them suitable for vaccine development and gene therapy. Include a critical assessment of their limitations.
Explain adenovirus structure and ease of genetic manipulation.
Describe immune responses generated and durability of expression.
Analyse risks like pre-existing immunity and inflammation.
Review improvements in gutless or non-replicative vectors.
Evaluate how knowledge of virus uncoating has advanced our ability to interfere with early stages of infection.
Outline the steps in viral uncoating after cell entry.
Discuss the role of capsid disassembly and genome release.
Provide examples of drugs targeting uncoating (e.g., amantadine for Influenza).
Consider challenges in targeting a dynamic and rapid process.
Describe how virus entry strategies have been elucidated using structural methods. How has this shaped antiviral design?
Highlight cryo-EM and X-ray crystallography in studying entry proteins.
Provide examples of structure-informed inhibitors (e.g., fusion blockers).
Discuss the significance of understanding receptor-binding domains.
Analyse how knowledge of conformational transitions informs therapeutic targets.
Critically assess how the host immune system detects and responds to viral entry, and how viruses avoid these responses.
Describe PRRs involved in detecting viral entry (e.g., TLRs, RIG-I).
Outline interferon responses and antiviral state induction.
Provide examples of viral proteins that antagonize detection.
Discuss the arms race between detection and evasion strategies.
How do positive-strand RNA viruses modify host organelles to create replication compartments? Why are these compartments important?
Explain membrane remodelling by viral proteins.
Provide examples (e.g., double membrane vesicles in coronaviruses).
Describe how compartments protect RNA and concentrate factors.
Discuss potential antiviral targets in membrane-modifying enzymes.
Describe the process of antiviral drug discovery and how advances in structural biology and bioinformatics have accelerated this pipeline.
Outline steps: target identification, screening, lead optimization.
Discuss role of structure-based drug design.
Highlight use of computational modelling and AI tools.
Provide examples of successful drugs discovered through these methods.
Evaluate how viral structural plasticity affects both immune escape and antiviral resistance.
Define structural plasticity and conformational masking.
Explain its role in antibody escape (e.g., HIV-1 Env, RSV F).
Describe how resistance mutations alter drug-binding sites.
Discuss challenges this poses for vaccine and drug development.
Compare the effectiveness of traditional vaccines with structure-based vaccine approaches in controlling rapidly evolving viruses.
Define principles of traditional live-attenuated or inactivated vaccines.
Describe structure-based approaches using stabilized epitopes.
Use examples (e.g., RSV, Influenza, HIV).
Evaluate pros and cons of each strategy in the face of viral evolution.
Describe how RNA interference (RNAi) functions as an antiviral defence mechanism and discuss how viruses counteract this response.
Explain the RNAi pathway: DICER processing and RISC-mediated cleavage.
Discuss how RNAi suppresses viral replication in plants and insects.
Describe viral suppressors of RNAi (e.g., VSR proteins).
Explore the potential of RNAi in antiviral therapy.
Critically assess how viral genome structure and replication strategy influence the formation of replication compartments in positive-strand RNA viruses.
Describe typical replication organelles and their formation.
Explain how genome structure directs localization and assembly.
Compare replication strategies across viruses (e.g., Dengue vs Poliovirus).
Discuss implications for targeting replication with antivirals.
Discuss how structural vaccinology can aid in the design of universal vaccines for highly variable viruses like influenza.
Define conserved structural epitopes (e.g., HA stem domain).
Explain rational antigen design using structural data.
Analyse limitations of current flu vaccines and need for broader immunity.
Provide examples of current universal flu vaccine candidates.
Evaluate the impact of viral protease function on the viral life cycle and how protease inhibitors can act as effective antiviral agents.
Describe roles of proteases in polyprotein processing (e.g., HIV, HCV).
Explain timing and regulation of protease activity.
Discuss design of small molecule inhibitors (e.g., ritonavir, telaprevir).
Address resistance mutations and combination therapy.
Examine the mechanisms by which non-enveloped viruses achieve cell entry and genome delivery without membrane fusion.
Describe receptor binding and endocytosis mechanisms.
Explain how pH or protease triggers capsid rearrangement or lysis.
Provide examples (e.g., Adenovirus, Poliovirus).
Discuss implications for vector design and immune recognition.
