Viruses have evolved clever ways to sneak into our cells. They latch onto specific receptors, hitch a ride through the cell membrane, and then shed their outer layers. It's like a molecular heist, with viruses using our own cellular machinery against us.
Once inside, viruses unpack their genetic cargo, ready to hijack our cells. This process varies between enveloped and non-enveloped viruses, influencing how they spread and survive. Understanding these entry tricks is key to stopping viral invasions.
Viral Entry Mechanisms
Attachment and Receptor Interactions
- Viral attachment involves specific interactions between viral surface proteins (ligands) and host cell receptors, initiating the entry process
- Viruses exploit existing cellular uptake pathways (clathrin-mediated endocytosis, caveolin-dependent endocytosis)
- Some viruses induce macropinocytosis where cell membrane ruffles and engulfs large volumes of extracellular fluid containing viral particles
- Choice of entry mechanism depends on virus structure, host cell type, and environmental factors
- Examples of viral ligands include:
- Hemagglutinin in influenza viruses
- Spike protein in coronaviruses
- Host cell receptors examples:
- ACE2 for SARS-CoV-2
- CD4 for HIV
Endocytosis and Membrane Fusion
- Endocytosis internalizes virus within a vesicle, often triggered by receptor binding
- Membrane fusion utilized by enveloped viruses merges viral envelope with host cell membrane
- Direct penetration used by some viruses injects genetic material through cell membrane without full internalization
- Endocytosis pathways include:
- Clathrin-mediated endocytosis (influenza virus)
- Caveolin-dependent endocytosis (SV40 virus)
- Membrane fusion examples:
- HIV uses gp41 protein for fusion at the cell surface
- Influenza virus fuses within endosomes after pH-induced conformational changes
Uncoating and Genetic Material Release
Uncoating Process and Mechanisms
- Uncoating releases viral genome from protective capsid into host cell cytoplasm or nucleus
- Enveloped viruses begin uncoating with fusion of viral envelope with cellular membranes, exposing nucleocapsid
- Non-enveloped viruses undergo conformational changes from cellular triggers, leading to capsid destabilization and genome release
- Endosomal acidification triggers conformational changes in viral proteins, crucial for many uncoating processes
- Some viruses use host cell proteases to degrade capsid proteins, facilitating genome release
- Uncoating may occur in stages:
- Partial disassembly at cell surface or in endosomes
- Complete genome release in cytoplasm or nucleus
Timing and Cellular Factors
- Timing and location of uncoating critical for successful viral replication
- Uncoating process influences host's ability to detect and respond to infection
- Cellular factors involved in uncoating:
- pH changes in endosomes (influenza virus)
- Cellular chaperones (adenovirus)
- Proteasome activity (reovirus)
- Examples of uncoating locations:
- Poliovirus uncoats in the cytoplasm
- Herpesvirus uncoats at the nuclear pore
Enveloped vs Non-enveloped Entry
Structural Differences and Entry Strategies
- Enveloped viruses possess lipid bilayer from host cell membranes, non-enveloped viruses lack outer membrane
- Enveloped viruses enter through membrane fusion at cell surface or within endosomes, using viral fusion proteins
- Non-enveloped viruses enter through endocytosis followed by membrane penetration or pore formation in endosomal membrane
- Enveloped viruses exploit cellular membrane fusion machinery
- Non-enveloped viruses rely on capsid protein conformational changes for entry
- Examples of enveloped viruses:
- Influenza virus
- HIV
- Coronavirus
- Examples of non-enveloped viruses:
- Adenovirus
- Poliovirus
- Rotavirus
Uncoating and Environmental Stability
- Enveloped virus uncoating begins with envelope fusion
- Non-enveloped viruses require more extensive capsid disassembly for uncoating
- Enveloped viruses more susceptible to environmental factors and disinfectants due to lipid envelope
- Non-enveloped viruses tend to be more stable in various environments
- Both types can use receptor-mediated endocytosis, but subsequent steps in cell entry and uncoating differ significantly
- Environmental stability examples:
- Influenza virus (enveloped) survives on surfaces for hours
- Norovirus (non-enveloped) can persist for weeks on surfaces
Host Cell Receptors and Tropism
Receptor Function and Viral Tropism
- Host cell receptors are specific molecules on cell surface that viruses recognize and bind to, initiating entry process
- Distribution and abundance of specific receptors on different cell types determine viral tropism, influencing infectable tissues
- Receptor binding often triggers conformational changes in viral proteins, facilitating subsequent entry steps
- Some viruses use multiple receptors or co-receptors, affecting ability to infect different cell types or species
- Affinity and specificity of virus-receptor interactions influence efficiency of viral entry and overall infection course
- Examples of receptor-mediated tropism:
- HIV targets CD4+ T cells using CD4 and chemokine receptors
- Hepatitis B virus targets liver cells using sodium taurocholate cotransporting polypeptide (NTCP)
Evolutionary Aspects and Therapeutic Implications
- Evolutionary changes in viral surface proteins can alter receptor usage, potentially changing host range or tissue tropism
- Understanding virus-receptor interactions crucial for developing antiviral strategies (entry inhibitors, receptor decoys)
- Receptor binding sites often conserved, making them potential targets for broad-spectrum antivirals
- Examples of receptor-based antiviral strategies:
- Maraviroc blocks HIV entry by targeting CCR5 co-receptor
- Neutralizing antibodies against viral attachment proteins (influenza hemagglutinin)