Virology 3: Viral Replication Flashcards
What is a Virion
The complete, infective form of a virus outside a host cell, with a core of RNA or DNA and a capsid.
Viral replication cycle in host cell steps
- Attachment
- Penetration
- uncoating
- Transcription of early mRNA
- Translation of early proteins
- Replication of viral DNA
- Transcription of Late DNA
- Translation of late proteins
- Assembly of Virions
- Release
What is attachment? What mediates this process?
Virus recognition of target cells.
Mediated by two molecules:
1. VAPs on surface of virion
2. receptor of target cell
What are VAPs on different types of viruses?
Viral attachment protein:
-Non-enveloped: part of capsid or protein extending from capsid
-Enveloped Virus: Spike/ peplomer glycoproteins on the envelope.
What are host cell receptors and what is their significance to the virus?
What they are:
- Proteins
- carbohydrates on glycoproteins
- glycolipids on the cell surface.
What their significance is:
- Assist with the virus recognizing the target cell.
-determine host range and tissue tropism
What is tissue tropism?
Range of cells and tissues of a host that support growth of a particular pathogen
What is Penetration? What are types of penetration?
After attachment: Energy dependent and rapid.
- Enters through 3 mechanisms:
1. Fusion: Enveloped
2. Endocytosis: Enveloped
3. Translocation: Non-enveloped
Fusion penetration
Enveloped Viruses
Vesicle the virus is in fuses with cell membrane to release virus inside
Endocytosis penetration
Enveloped viruses
Wraps virus in a vesicle made from cell membrane. Usually combines with lysosome to destroy cell.
Translocation penetration
Non-enveloped virus
Simply passes through
What happens during uncoating?
- Nucleocapsid is disintegrates
- genome is freed in cytoplasm
- proteins are disintegrated in cytoplasm
- Synthesis of viral proteins by cellular metabolism can occur
What happens during translation or viral proteins?
-Viral genome is translated into viral protein using host cell mechanics.
What are the steps of Macromolecular Synthesis?
transcription, translation, post-translational modification, and viral genome replication
What are post-translation modifications to mature a viral protein?
- Phosphorylation (nucleic acid binding)
-Fatty Acid acylation (membrane insertion) - Glycosylation
- Proteolytic cleavage
Where does macromolecular synthesis occur for DNA viruses?
-Nucleus
- Use host cell RNA polymerase II and other enzymes to transcribe viral mRNA
Where does macromolecular synthesis occur for RNA viruses?
-Cytoplasm
-Virus must encode for enzymes used in transcription and replication in their genomes
What occurs during assembly of virions?
- Viral matrix protein drags viral nucleocapsid toward membrane
- Brings toward membrane in area fused with viral glycoproteins
- Combining proteins made with replicated DNA
What occurs during maturation of virion?
The cell membrane area with the viral glycoproteins will begin to bud and pinch
*At this point a non-enveloped virus will combine with lysozyme to release
What occurs during release of virion?
The cell membrane is pinched to create free infectious virion.
*** The virion took the portion of the cell membrane that it replaced the proteins with viral proteins.
Describe the whole viral life cycle
See image
What is cytopathic effect (CPE)?
Morphological changes of infected cells in vitro such as-
-Rounding (shrinking)
- Lysis (cell death)
- Detachment (from mother)
- Syncytia (Cells fusing)
- Inclusion bodies
What does viral replication cause in vivo vs in vitro?
In vivo: diseases
In vitro: Cytopathic effects (CPE)
What causes cytopathic effects (CPE)?
- Direct injury to cell from virus infecting cells
- Side effect from altered metabolism due to virus infecting other cells in the body
What are the effects of viruses on cellular metabolism?
Inhibition of:
1. Cellular transcription mechanisms
2. RNA processing pathways
3. Cellular translation
4. Host cell DNA synthesis
pretty much the virus is using all this machinery
What are the effects of viruses on cell structures?
- Membrane fusion of neighboring cells
- Changing the permeability of cell plasma membrane
- Disruption of cytoskeletal fiber systems, microfilaments, and microtubules
- Cytoskeletal components incorporated into infected cell structures.
What does membrane fusion of neighboring cells lead to?
Syncytia- many nuclei
- Common characteristic of CPE for several enveloped viruses
What does changing the permeability of cell plasma membrane lead to?
Increased influx of various ion/toxins causing cell lysis.
What does disruption of cytoskeletal fiber systems, microfilaments, and microtubules lead to?
Rounding/shrinking of cells.
- Common characteristic of CPE
What does Cytoskeletal components incorporated into infected cell structures lead to?
Inclusion bodies either in the cytoplasm or nucleus.
What type of virus forms inclusion body in the cytoplasm?
RNA virus
What type of virus forms inclusion body in the nucleus?
DNA virus
What is an inclusion body
Unique structures generated by viral proteins together with some cellular proteins as a platform for efficient viral replication
Ways for virus to enter host
Respiratory tract
GI tract
Conjuctiva
Genitourinary tract
Skin (epidermis)
Viral replication must occur in what kind of cells?
Living
Characteristics of viral entry through skin
- Barrier: Epidermis, outer keratinized layer of dead cells - virus cant enter
- Penetration/loss of barrier (cut, bite) - virus can enter
- Local infection can spread to systemic infection
Characteristics of viral entry through respiratory tract
AEROSOLS
- Barriers: mucus, mucocillia, WBCs, IgA, Cell mediated immunity
- Factors: droplet size, air currents, humidity, temperature (cold)
Characteristics of viral entry through GI tract
- Barriers: Low pH (acidic), proteases, bile salts, mucus, igA, cell-mediated immunity
- Factors: in some cases GI enzymes enhance viral infectivity
What type of virus can survive the stomach acidity?
Non-enveloped
Characteristics of viral entry through genitourinary tract
Barriers: mucus, IgA, cell-mediated immunity
Characteristics of viral entry through conjuctiva
Barriers: tears containing IgA and IgG
** Not a major route of transmission
Infections of the skin will lead to
only local infection cell-to-cell spread. Can not penetrate skin barrier
What is systemic infection and what are the types?
Spread of infection to distant tissues through
1. Hematogenous
2. lymphatic
3. Neural
What is a viremia?
Virus circulating in the blood
High viremia = virulence
Hematogenous spread-
Where does it enter?
Where does it go?
Is it effective?
- Enters through a epithelial surface where replication is limited
- Primary viremia (small amount of virus) moves to Vascular system (major pathways leading to systemic spread)
- Primary viremia reaches distant organs (major replication sites)
- Secondary viremia (large amount) enters vascular system leading to major clinical signs
*Very effective
Lymphatic spread-
Where does it enter?
Where does it go?
Is it effective?
- Enters through epithelial cells, vascular system.
- Replicates in local aqueous site
- Spreads through draining lymph to other tissues
*Ineffective
Neural spread-
Where does it enter?
Where does it go?
What is the speed?
- Enters from viremia infections
- Infectivity dependent on nerve tissue exposure
- Transport speed: 2-16 mm/day along the nerve axons
