L5 - Viral Entry Flashcards
What is the significance of virus entry in the viral life cycle?
Virus entry is an essential step to establish infection as it allows the virus to bind, penetrate, and ultimately replicate within the host cell.
How do viruses achieve high local concentration on the cell surface?
They attach through multiple, low‐affinity receptor–virus interactions that stably concentrate virus particles on the cell surface.
What are the two general pathways a virus may follow after receptor binding?
Viruses may fuse directly at the plasma membrane or be internalised via endocytosis/macropinocytosis, remaining within a vesicle.
How does the virus escape from an endosomal compartment?
Escape occurs either by fusion of the viral and vesicular membranes or by disrupting the vesicle’s integrity.
What types of molecules serve as viral receptors and attachment factors?
They include proteins, glycoproteins, glycolipids, and sometimes carbohydrates such as heparan sulphate and sialic acids.
How do attachment factors differ from true viral receptors?
Attachment factors are non-essential, low-affinity, and serve primarily to concentrate virus particles, whereas receptors trigger entry via specific binding.
Why is multivalency important in virus–cell interactions?
Multivalent binding increases overall binding avidity, ensuring stable attachment despite individual low-affinity interactions.
In what way can receptor clustering influence viral uptake?
Clustering can induce signalling (e.g. via receptor tyrosine kinases) that promotes endocytosis or direct fusion.
Which uptake mechanisms allow viruses to enter host cells while enclosed in vesicles?
Clathrin-mediated endocytosis and macropinocytosis are key mechanisms for virus internalisation.
How does macropinocytosis differ from receptor-mediated endocytosis?
Macropinocytosis involves the non-specific “cell drinking” of extracellular fluid, while receptor-mediated endocytosis is a targeted, receptor-triggered process.
What role does the cellular environment (such as pH) play in viral uptake?
A drop in pH within endosomes can trigger conformational changes in viral proteins necessary for membrane fusion.
Why must viruses traffic to specific endosomal compartments?
Specific compartments provide the correct conditions—like low pH or particular enzymes—to facilitate viral fusion or uncoating.
What is the role of viral fusion proteins during entry?
Fusion proteins catalyse the merging of the viral envelope with the host cell membrane, enabling the delivery of the viral genome into the cytosol.
How is fusion at the plasma membrane initiated for enveloped viruses?
It is initiated by a dedicated fusion protein—often activated by receptor binding—that undergoes a conformational change exposing a fusion peptide.
What triggers fusion within the endosomal compartment?
A decrease in pH in the late endosome induces structural rearrangements in the fusion protein, exposing the fusion peptide.
What distinguishes Class I, II, and III fusion proteins?
They differ in structure and activation: Class I proteins are cleaved to expose an amino‐terminal fusion peptide; Class II proteins use an internal fusion peptide and form dimers that rearrange at low pH; Class III proteins combine features of both, often with reversible conformational changes.
How do non-enveloped viruses typically enter host cells without membrane fusion?
They rely on mechanisms such as endocytosis followed by the formation of membrane pores or disruption of the endosomal membrane.
What role does capsid reorganisation play in non-enveloped virus entry?
Reorganisation exposes hydrophobic domains or peptides that interact with and destabilise the host membrane to allow genome release.
Why is receptor-mediated attachment still critical for non-enveloped viruses?
It concentrates viruses on the cell surface and may trigger endocytic uptake despite the absence of a viral envelope.
What is a key difference between the entry mechanisms of enveloped and non-enveloped viruses?
Enveloped viruses use fusion proteins for membrane merging, whereas non-enveloped viruses typically form pores or cause mechanical disruption of the endosome.
What are the key steps involved in viral entry into host cells?
The key steps include attachment to host cell receptors, uptake via endocytosis or direct fusion, and genome release into the cytoplasm.
How does the specificity of receptor binding influence viral tropism?
Receptor binding determines which cells a virus can infect, influencing host and tissue specificity.
What distinguishes true viral receptors from attachment factors?
True receptors facilitate viral entry, while attachment factors merely enhance viral concentration on the cell surface.
How does receptor-mediated endocytosis facilitate viral entry?
Endocytosis allows viruses to enter vesicles, where pH changes trigger fusion with the endosomal membrane, releasing the genome.
Why do some viruses utilize direct fusion at the plasma membrane?
Direct fusion enables viruses to bypass endosomal processing by merging directly with the host cell membrane.
How does pH influence the viral entry process?
A drop in pH within endosomes triggers conformational changes in viral proteins, facilitating membrane fusion.
What role do viral glycoproteins play in membrane fusion?
Viral glycoproteins mediate binding to receptors and undergo structural changes to drive membrane fusion.
Why is proteolytic cleavage of viral proteins important for entry?
Cleavage activates fusion proteins, allowing them to adopt conformations necessary for membrane insertion.
How do host proteases contribute to viral infection?
Host proteases process viral proteins, activating them for successful entry into the host cell.
What is the significance of structural studies in understanding viral entry?
Structural studies provide molecular-level insights into how viruses attach, fuse, and enter cells.
How has cryo-electron microscopy advanced our understanding of viral entry mechanisms?
Cryo-EM has revealed high-resolution details of viral fusion proteins and their conformational changes.
What structural changes occur in viral proteins during fusion?
Fusion proteins undergo rearrangements that expose fusion peptides, enabling membrane merging.
Why are helical bundles important in viral membrane fusion?
Helical bundles bring viral and host membranes into close proximity, facilitating fusion.
How does knowledge of viral entry contribute to vaccine development?
Understanding key viral proteins helps design vaccines that elicit protective immune responses.
How can antiviral drugs target the viral entry process?
Drugs can block receptor binding, fusion, or endocytosis, preventing viral entry.
How has AlphaFold contributed to predicting viral protein structures?
AlphaFold predicts viral protein structures, accelerating drug discovery and vaccine design.
What insights into viral fusion have been gained from SARS-CoV-2 studies?
SARS-CoV-2 studies have shown how spike protein rearrangements facilitate entry into host cells.
Why is the coordination of viral entry processes critical for infection?
Precise timing of entry ensures viruses exploit optimal cellular conditions for infection.
How do changes in viral structure regulate the timing of entry?
Structural rearrangements regulate when and where a virus can fuse with host membranes.
What are the implications of viral entry studies for public health?
Viral entry research informs strategies to prevent infections and develop effective treatments.
Why is the spatial and temporal regulation of viral entry important?
It ensures that fusion or uncoating only occurs at the right time and place within the cell, preventing premature genome release or degradation.
How can viruses actively trigger their own internalisation?
By engaging receptors that activate signalling pathways (e.g. receptor tyrosine kinases) which promote endocytosis.
Besides membrane fusion, how else can viruses escape endosomes?
They may disrupt the endosomal membrane or form pores via capsid rearrangements to release their genome.
What is the role of co-receptors in viral entry?
Co-receptors assist primary receptors by stabilising virus binding or triggering conformational changes that promote entry.
How does the lipid composition of host membranes affect viral fusion?
Certain lipids like cholesterol and sphingolipids help organise receptors and facilitate membrane curvature for fusion.
What happens after viral fusion or endosomal escape?
The viral capsid is uncoated, and the genome is released into the cytoplasm or transported to the nucleus.
How does Influenza virus enter host cells?
It binds to sialic acid and is internalised by endocytosis; low pH in endosomes triggers fusion.
How does HIV enter host cells?
HIV binds CD4 and a co-receptor (CCR5 or CXCR4), triggering conformational changes that mediate fusion at the plasma membrane.
What is Enfuvirtide and how does it block viral entry?
Enfuvirtide is an HIV fusion inhibitor that mimics part of gp41 and prevents the virus from fusing with the host membrane.
What is Maraviroc and how does it prevent HIV infection?
Maraviroc is a CCR5 antagonist that blocks HIV from binding the co-receptor needed for entry into host cells.
How does Foscarnet act as an antiviral drug?
Foscarnet is a pyrophosphate analog that directly inhibits viral DNA polymerase by binding the pyrophosphate-binding site.
When is Foscarnet used clinically?
It is used when resistance has developed to acyclovir or ganciclovir, especially in CMV or HSV infections.
What is the role of combination therapy in antiviral treatment?
It improves efficacy and reduces the risk of resistance, especially in chronic infections like HIV and HCV.
What drugs are used in HIV pre-exposure prophylaxis (PrEP)?
Tenofovir and Emtricitabine are used in combination to prevent HIV infection in high-risk individuals.
How does combination therapy help treat HCV?
It overcomes rapid viral mutation by targeting multiple steps in the replication cycle, often with drugs like Sofosbuvir and Ledipasvir.
Why is resistance testing important before starting HIV treatment?
It helps identify existing drug-resistant strains and guides selection of effective antiviral combinations.
What is a prodrug and why is it used in antiviral therapy?
A prodrug is an inactive compound that is metabolised into an active drug form in the body, improving absorption and bioavailability.
Why is polymerase selectivity important in antiviral drug design?
Selectivity for viral over host polymerases reduces toxicity and increases therapeutic effectiveness.
Why is HBV difficult to cure?
HBV forms covalently closed circular DNA (cccDNA) in the nucleus, which persists and resists clearance even during treatment.
