Virus Entry Flashcards
What is virus entry
Virus entry is an essential step in the viral life cycle that allows the virus to establish infection within a host cell
What is the purpose of virus-cell attachment
Virus-cell attachment enriches viruses on the cell surface and stabilizes them through multiple receptor-virus interactions
What happens after a virus binds to cell surface receptors
After receptor binding, viruses can:
1) Fuse directly at the plasma membrane and uncoat
2) Be internalised through endocytosis and macropinocytosis, remaining in vesicles inside the cell
How do viruses escape from endosomes into they cytosol
Viruses escape their envelope with the vesicle membrane by either:
1) Fusing their envelop with the vesicle membrane
2) Disrupting or breaking the vesicle membrane
Where are the internalised viruses trafficked inside the cell
Internalised viruses are transported to specific endosomal pathways such as:
- The late endosome/lysosome pathway
- The retrograde trafficking pathway to the trans Golgi network
What are the steps of virus entry
1) Binding
2) Lateral diffusion
3) Signaling
4) Internalisation
5) Vesicular transport
6) Membrane Penetration
7) Intra-cytosolic transport - via microtubules
8) Nuclear import
9) Uncoating
What kinds of molecules can serve as viral receptors or attachment factors
Proteins
Glycoproteins
Glycolipids
These molecules are found on the cell surface and may be abundant or cell-type specific, influencing which cells a virus can infect.
Can viruses use more than one receptor or attachment factor
Yes
Viruses often use:
- Multiple receptors/attachment factors, sometimes depending on the cell type.
- A primary receptor for main binding and a co-receptor to facilitate entry.
What mediates the attachment of viruses to host cells
Electrostatic interactions primarily mediate attachment. These are influenced by:
- Ionic strength
- pH
Presence of specific ions
This attachment is often reversible, allowing viruses to detach if conditions aren’t favorable.
How do non-enveloped viruses attach to host cells
Non-enveloped viruses use surface structures (such as capsid spikes or knobs) to attach to cellular receptors.
Adenoviruses use fiber proteins projecting from their capsids to engage receptors like CAR
How do enveloped viruses attach to host cells
Enveloped viruses use envelope glycoproteins to bind host receptors. These glycoproteins are embedded in the viral envelope and mediate both attachment and fusion with host membranes.
What are the structures found on the surface of host cells
Attachment factors
Receptors
How do viral receptors on the cell surface interact with a virus
Viral receptors interact directly with the virus
These interactions are often multi-valent, meaning multiple binding sites contribute to the overall attachment
This increases the binding stability, even if individual interactions are weak
What is the nature of viral receptor binding
Viral binding to receptors is typically:
Highly specific (the virus recognizes particular receptor structures).
Low affinity at a single binding site, but strengthened by multivalent interactions.
What happens once the virus is stably attached to the cell surface
The virus induces signals in the host cell.
These signals prepare the cell for viral entry and may involve:
- Cytoskeletal rearrangements
- Changes in receptor conformation
- Activation of endocytic pathways
How does receptor binding promote viral entry
Once bound, the virus can enter the cell via:
- Endocytosis/macropinocytosis – the cell engulfs the virus into a vesicle.
- Membrane fusion – the viral envelope merges with the cell membrane, releasing the genome inside.
What are the virus attachment factors
Attachment factors are non-essential host cell surface molecules that help viruses bind loosely to the cell surface.
They are not required for entry but play a supportive role in concentrating the virus near entry receptors.
What are the binding characteristics of viral attachment factors
The interactions between viruses and attachment factors are:
Non-specific
Low-affinity
These weak, reversible interactions help retain the virus near the cell long enough to engage specific receptors.
What are some examples of common virus attachment factors
Heparan sulfate proteoglycans (HSPGs)
Carbohydrates
Sialic acids
What role does influenza virus hemagglutinin (HA) play in host cell entry
Influenza virus HA (hemagglutinin) is an envelope glycoprotein that binds to sialic acid-containing receptors on the host cell surface.
This multivalent binding increases attachment strength and stability.
What is receptor clustering in influenza virus entry
HA binding to multiple sialic acid receptors causes receptor clustering on the cell surface.
This clustering can bring together receptors and co-receptors, forming a platform that facilitates signaling and virus uptake.
How does receptor clustering by HA trigger host cell signaling
Clustered receptors can activate intracellular signaling pathways, such as:
- Receptor Tyrosine Kinases (RTKs) like EGFR (Epidermal Growth Factor Receptor)
- Voltage-gated calcium channels, like Cav1.2
These signals help remodel the cytoskeleton, open endocytic pathways, and prepare the cell for virus internalization.
What does cellular uptake mean in the context of influenza virus entry
After HA binding and receptor signaling, the virus is taken into the cell by endocytosis.
Why must the influenza virus traffic to specific intracellular compartments after uptake
Influenza must reach acidic endosomal compartments where the low pH triggers conformational change in HA.
This allows HA to mediate membrane fusion, releasing the viral genome into the cytosol for replication.
What are the 2 virus uptake mechanisms
1) Receptor mediated endocytosis
2) Receptor mediated signalling - fusion
What are the steps to the endocytosis pathway
1) Attachment via Receptor-mediated endocytosis
2) Internalization into vesicles
3) Intracellular trafficking
4) Fusion within Endosomes
5) Penetration and Uncoating
What does attachment via receptor-mediated endocytosis include
The virus is now enclosed in an endosome or pinosome (intracellular vesicle).
This allows the virus to avoid immune detection and prepare for fusion/penetration from within the host.
What does the intracellular trafficking include
The endocytic vesicle carrying the virus travels along the microtubule network, using motor proteins like dynein and myosin.
The vesicle matures (early endosome → late endosome).
What does fusion within endosome entail
Inside the endosome, pH drops (acidification), triggering conformational changes in viral proteins.
This allows fusion of the viral envelope with the endosomal membrane.
- pH-dependent fusion: Requires low pH to trigger.
- pH-independent fusion: Does not require acidification.
What does the penetration and uncoating of the virus entail
Viral genome is released into the cytosol via:
- Fusion (for enveloped viruses).
- Endosome rupture or pore formation (for some non-enveloped viruses).
Uncoating = disassembly of the viral capsid to release the genome for replication.
What are the steps for direct fusion pathway
1) Attachment and signaling
2) Membrane fusions at the surface
3) Penetration and uncoating
What does the attachment and signaling step in the direct fusion include
The virus binds directly to receptors on the plasma membrane.
This triggers signaling cascades, such as:
- Receptor Tyrosine Kinases (RTKs) like EGFR.
- Changes in Ca²⁺ levels via voltage-gated calcium channels (e.g., Cav1.2).
What does membrane fusion at the surface in direct fusion entail
The virus fuses directly with the plasma membrane without being internalized into a vesicle.
This is often pH-independent (doesn’t require acidification).
The cytoskeletal actin cortex may disassemble locally to permit fusion
What does the penetration and uncoating step entail in direct fusion of the virus
After fusion, the viral core is released directly into the cytosol.
Capsid disassembly (uncoating) follows to expose the viral genome.
How does Ca2+ contribute to viral entry
Calcium ions regulate membrane fusion, cytoskeletal dynamics, and endocytic vesicle formation.
Virus-induced signaling can activate voltage-gated calcium channels (like Cav1.2), facilitating entry.
What roles do actin and microtubules play in virus uptake
Actin filaments support receptor clustering and membrane remodeling during endocytosis.
Microtubules and motor proteins like dynein and myosin help traffic endocytic vesicles toward the cell interior and nucleus.
Why are ions like K+ important in viral entry
Changes in intracellular ion concentrations (e.g., K⁺ efflux) can activate viral entry or uncoating steps and influence endosome maturation.
What is the role of host enzymes and proteases in virla
Host proteases cleave viral envelope proteins, activating fusion peptides or preparing the virus for uncoating.
What roles do chaperones and disaggregation machinery play in viral uncoating?
These host factors help disassemble the viral capsid, releasing the genome into the cytosol.
They may also help resolve aggregated protein complexes formed during entry.
What does “cross-talk with the cytosol” refer to in virus entry?
Once in the cytosol, viruses interact with host signaling pathways that regulate translation, immunity, and replication.
This cross-talk helps them establish infection and avoid detection.
What is the difference between the virus entry mechanisms of enveloped viruses and non-enveloped viruses?
Enveloped viruses fuse their lipid bilayer with the host cell membrane, releasing their genome into the cell.
Non-enveloped viruses penetrate the host cell by disrupting the membrane, forming pores, or other non-fusion methods.
How does the virus initially attach to the host cell in the case of enveloped viruses?
The virus has glycoproteins (GP) on its surface.
These glycoproteins bind to specific receptors on the host cell surface, referred to as Cue.
This binding is crucial for viral entry into the host cell.
What happens during the hemifusion stage of viral entry for enveloped viruses?
After the virus binds to the host cell, the viral envelope fuses with the outer leaflet of the host cell membrane, forming hemifusion.
At this stage, the outer membrane leaflets of both the virus and host cell merge, but the inner leaflets remain separate.
What occurs after hemifusion during the viral entry of enveloped viruses?
The fusion process completes, and the full fusion of the viral envelope with the host cell membrane occurs.
This results in the viral genome being released into the host cell’s cytoplasm for replication and viral assembly.
How do non-enveloped viruses penetrate the host cell membrane?
Non-enveloped viruses create pores in the host cell membrane using structural proteins, allowing the viral genome to enter the host cell.
These pores are formed by specific interactions between the viral capsid and the host membrane.
