Intro to viruses Flashcards
Description of viruses
1. Small, obligate intracellular pathogens
- Filterable agent
- not visible by light microscopy
2. no subcellular organelles
3. replicate only in living cells
- can not be cultured like bacteria
- rely on host cell protein synthesis machinery
4. New viral particles (virions) are assembled, the virus does not divide
Components of a virus
Composition of viruses (naked vs.. enveloped viruses)
1. Naked Viruses
DNA/RNA + Structural Proteins (Capsid proteins) +/- Enzymes and Nucleic acid-associated proteins = Nucleocapsid
2. Enveloped Viruses:
Nucleocapsid + glycoproteins & membrane = Enveloped virus
Naming Viruses:
- After clinical conditions
Naming Viruses:
- After their location of discovery
Naming Viruses:
- After their properties
&
- After people
Basis of “Baltimore classificaton system” and what are the classes
Baltimore classification system
- Based on the type of nucleic acid genome & replication strategy of the virus
- Type of nucleic acid dictates replication strategy
Classes:
- I: dsDNA viruses
- II: ssDNA viruses
- III: dsRNA viruses
- IV: positive-sense ssRNA viruses (+ssRNA)
- V: negative-sense ssRNA viruses (-ssRNA)
- VI: RNA viruses that reverse transcribe
- VII: DNA viruses that reverse transcribe
Classification of medically important DNA viruses
Classification of medically important RNA viruses
How do viruses infect cells?
- Attachment
* Can’t infect a cell if it can’t bind to that cell
2. Entry/uncoating
- Genome needs to be released into the host cell
3. Macromolecular synthesis
- Viral proteins get transcribed/translated
- Genome gets copied (replicated)
4. Assembly & release
- New viral particles self assemble
- Released from the host cell & spread to infect new cells
DNA vs. RNA Viruses
What are the clinical consequences of different types of genomes in viruses?
- DNA viruses and retroviruses
- Transformation
- Latent infections
- RNA viruses:
* Variability ==> “quasi-species” ==> Immune escape variants
Different capsid in viruses
- Helical
- Icosahedron
- Complex
- Poxviruses
- Oval shaped virus with dumbell shaped capsid
What are the functions of the viral capsid?
- Protect the genome
2. In naked viruses – involved in attachment
- Involved in entry & uncoating
4. Involved in assembly
- package viral enzymes if necessary
Properties of Naked, Icosahedral viruses
They are tough!!!
- Can dry out and RETAIN infectivity
- Can survive the acidic consitions of GI tract
- Resistant to extreme temperatures, detergents and poor sewage treatment
- Typically* released via cell lyses
- Survival in environment enables transmission via fomites
* difficult to disinfect contaminated surfaces - Survival in GI tract enables transmission via fecal-oral route
- shed in stool
- present in sewage/contaminated water
- responsible for most cases of viral gastroenteritis
- Cytopathic
* cell undergoes morpholical changes after addition of virus
Describe the viral envelop
- Host derived lipid membrane
- Viral encoded proteins
- Matrix proteins = for assembly
- Surface (envelope) glycoproteins
- viral assembly
- virus-cell fusion
- induce neutralizing (protective) antibody
Properties of enveloped viruses
- must stay wet to retain infectivity
- Acid and heat labile
* acid and heat causes destruction of virus - Infectivity is destroyed by organic solvents and detergents
- Released by budding (may cause cell lysis over time)
clinical properties of enveloped viruses
Remeber they must be wet to be infective
- Transmitted via respiratory droplets and secretions
- respiratory route
- blood
- organ transplant
- Cannot survive in the GI tract (Usually*)
* Not transmitted fecally or orally - Does not need to kill infected cell in order to spread
* Potential for persistance
Viral Replication
Steps in viral replication
- Attachment
- Entry and uncoating
- Macromolecule synthesis
- Transcription of viral genes
- Translation of viral proteins
- Replication of viral genome
- Assembly and release of new viral particles
5.
Attachment phase (in viral replication)
- Mediated by surface glycoproteins of enveloped viruses
- Mediated by capsid proteins of naked virions
- Important determinant of viral tropism
Viral Receptors
- Proteins or carbohydrates on cellular glycoproteins or glycolipids
- Physiological role in host cell
- Type of receptors:
- molecules involved in cell-cell interactions
- hormone, cytokine, or complement receptors
- enzymes
Viral Entry through PM
Naked vs Enveloped viruses
- Naked Viruses:
* Hydrophobic interactions create a channel through the membrane
- Enveloped viruses
* Hydrophobic domain (fusion peptide) in the attachment protein is exposed, following binding to a receptor or proteolytic cleavage at the plasma membrane
What are the 3 endocytotic pathways utilized by viruses?
- Phagocytosis
- Macropinocystosis
- Various endocytotic pathways:
- Clathrin-dependent endocytosis
- Caveolin-dependent endocystosis
- clarthrin and caveolin independent endocytosis
Clathrin-mediated vs Caveolin-mediated ENDOcytosis
Clathrin-mediated:
- pH-dependent entry into an endosome
- virus gets internalized from a region of the plasma membrane that contains a protein called clathrin, forming a “clathrin-coated pit”. The virus becomes enclosed within a vesicle called an endosome, which subsequently fuses with a lysosome. During this process, the pH of the endosome becomes more acidic. Some viral fusion proteins require exposure to either an acidic pH or lysosomal proteases to become activated so that they can mediate fusion between the viral envelop & the membrane of the endosome.
Caveolin-mediated:
- pH independent entry
- In caveolin-mediated endocytosis, virus becomes internalized at membrane invaginations that contain a protein called caveolin. These invaginations occur at a region in the plasma membrane that has a high density of relatively detergent-resistant lipids called lipid rafts. The vesicles containing virus fuse with other caveolin-containing vesicles forming a caveosome – these vesicles do not become acidified. Virus can be transported to other regions of the cell (such as the ER) before the genome is released into the cytosol.
Receptor mediated endocytosis of Naked, Icosahedral viruses
1. Viral capsid proteins form a pore through the endosomal membrane
- Viral capsid proteins lyse the endosomal membrane
- Conformational change in capsid proteins
- Expose a hydrophobic region (make a pore)
- Dissociate to release the genome (uncoating)
- Potential triggers for conformational change
- Acidic pH
- Proteolytic activity
- Receptor binding
Example of viral entry