2500_Virology_5 _w2025
Virus Entry Lecture
Instructor: Dr. J.D. Dikeakos, Schulich School of Medicine & Dentistry
Contact: jimmy.dikeakos@uwo.ca
Lecture Objectives
Main Objective: Understand how viruses enter host cells
Elements:
Overview and concepts of viral entry
Viral receptor attachment
Host cell entry mechanisms (enveloped and non-enveloped viruses)
Major Themes in Virology
For viruses to survive, they must:
Package their genome within a particle.
Transfer the genome from host to host using this particle.
Genome contains the information to initiate and complete the viral infectious cycle.
Establish themselves in hosts, ensuring long-term viral survival.
The GENOME is crucial for viral function, as established in the 1950s.
Overview of Viral Infectious Cycle
Key concept: Entry involves:
Recognition of host receptor (attachment).
Mechanism to release genome within the cytoplasm.
Passive Diffusion
Viruses are too large for passive transport through host cell membranes.
Stability of Virions
Virions must possess both stability and instability:
Stability varies through different stages of the infectious cycle.
Receptor Interactions
Viruses must find the "right" receptor:
Random electrostatic interactions do occur but do not initiate the infectious cycle.
The binding of a virus to its receptor triggers the infectious cycle and allows for genome release inside the host.
Definitions:
Susceptible cell: has functional receptor for the virus.
Permissive cell: allows virus replication.
Resistant cell: has no receptor.
Importance of Host Cell Receptors
Essential for many viruses, excluding yeast and plants.
Some viruses require a second receptor known as a co-receptor.
Variety of Host Cell Viral Receptors
All host cell viral receptors are surface membrane proteins.
A receptor can recognize multiple viruses, and multiple receptors can recognize a single virus.
Example: ACE2 Receptor
Key for the entry of SARS-CoV-2:
Various viruses use this receptor, with implications for viral infection.
Modes of Attachment
Non-enveloped vs. Enveloped Viruses
Attachment differs based on the outer structure of the virus.
Non-enveloped Viruses
Example: Picornaviridae (Poliovirus)
Structure: icosahedral symmetry with 60 VP proteins.
Single stranded RNA (+RNA) ready for infection.
Genome Release Mechanisms
Naked virions can release their genomes at the plasma membrane:
Poliovirus injects RNA across the membrane after capsid change, forming a channel.
Host Cell Entry Examples
Enveloped Viruses
Example: Influenza Virus
Hemagglutinin is a glycoprotein responsible for binding to host cell receptors (sialic acid).
Sialic Acid Linkages
2-3 linkages (avian) and 2-6 linkages (human) determine specificity for influenza strains.
Potential for Cross-species Infection
Avian influenza can bind to 2-3 sialic acid receptors in the lower respiratory tract, while human strains prefer the 2-6 linkages in upper and lower tracts.
Viral Entry Mechanisms
Viruses enter using cellular transport mechanisms, powered by molecular motors (active transport).
Release Triggers
Triggers for genome release depend on locations within the cell:
Can occur at the cell surface, early endosome, or late endosome.
pH Impact on Release Locations
Cell surface pH: 7.0
Early endosome pH: 6.0 - 6.5
Late endosome pH: 5.0 - 5.5
Non-enveloped Example: Reoviruses
Release linked to pH-induced capsid changes and hole formation in late endosomes.
Enveloped Virus Examples
Example: Paramyxoviridae (Measles)
Viral proteins mediate fusion events dependent on pH.
Ebola Virus Uptake
Utilizes Niemann–Pick C1 (NPC1) cholesterol transporter for infection in late endosomes.
Summary/Take-Home Message
Viruses recognize proteins on host cells for attachment, leading to viral entry and genome release at varied subcellular locations.