What are some characteristics of viruses?
Viruses ARE
- Infectious obligate intracellular parasites
- Particles with a DNA or RNA genome
- Agents that direct synthesis ofviral components using cellular systems
- Reproduced by de novo assembly
- Agents that create progeny particles for self transmission
What aren’t viruses?
Viruses are NOT
- Cells
- Autonomous organisms
- Prions
- Viroids
- Mobile genetic elements
- Alive
What are the parts of a virus?
- Genome: The RNA or DNA that carries the genetic information.
- Capsid: A protein shell surrounding and protecting the genome.
- Envelope: A lipid bilayer surrounding and protecting the capsid.
Viral surface glycoproteins are imbedded in the envelope. Not all viruses have envelopes (enveloped vs. naked)
What kind of variability is there among viruses?
Enveloped vs. naked
different kinds of capsids (complex with many kinds of proteins, immediately surrounding RNA, simple with only one kind of protein,
Shape
Kinds of proteins on the envelope
Kinds of genomes (linear, circular, linear mixed polarity, linear negative polarity, etc. etc. )
Size
How are viruses similar and how are they different to animal genomes?
- RNA viruses often have segmented genomes, like animal genomes, but the segments are much smaller (maybe one gene per segment)
- Sorting of segments is not always strict – Viral particles can have more or less than the minimum number of segments
- Most viral genomes are haploid, but Retroviruses are diploid
Why is viral taxonomy important and what are key features used in classification?
- Taxonomy is key to keeping the myriad of viral types clear and hence to guide treatment strategies.
- Key features for classification:
– Genome type and genetic organization
– Size and shape
– Presence or absence of an envelope
– Capsid symmetry
What are the six stages of viral replication?
A. Entry
- Attachment
- Penetration
B. Uncoating
C. Gene Expression
- Transcription
- Translation
D. Genomic Replication
E. Assembly
F. Release
What are the steps in positive polarity (mRNA) RNA viral replication?
The positive polarity RNA acts as mRNA and is translated in a large protein which is cleaved into smaller viral proteins (including RNA dependent RNA polymerase)
Negative polarity RNA is formed from the positive polarity RNA (transcription)
The negative polarity RNA is used to form lots of positive polarity RNA which is assembled with the viral proteins into a nuclear capsid.
What are the steps in negative polarity RNA viral replication?
Virus contains RNA dependent RNA polymerase
Negative polarity RNA is used to transcribe positive polarity RNA
Positive polarity RNA is used to translate viral proteins
Positive polarity is used for negative polarity RNA synthesis
Negative polarity RNA and viral proteins are assembled into nucleocaspids
How does viral attachment work? What is a very common way for antibodies to combat viruses?
Attachment is through specific interactions between the viral exterior (capsid or envelope glycoproteins) and receptors on the cell surface.
Neutralizing antibodies often block viral entry by binding the virus and interfering with attachment.
What is viral entry and uncoating?
•Entry: Virus crosses plasma membrane, usually by fusion or endocytosis.
•Uncoating: release of viral genome into the cytoplasm by membrane fusion, disassembly of capsid, or extrusion of genome. Not all viruses
uncoat (e.g., Rotavirus).
What are some characteristics of viral transcription?
•Transcription: Synthesis of RNAs for translation or direct function
– Mechanism is dependent on viral genome structure
– May use viral enzymes or cellular enzymes
– May occur in nucleus or cytoplasm
– May or may not produce mRNAs structured like cellular messages (no poly-A tail, etc….and thus require an alternate mechanism to be translated)
– Often regulated temporally to make different genes at different stages of the replication cycle
– Some viral RNAs are not translated, but function directly (e.g., Adenovirus VA RNA)
What are 3 general alternate translational pathways that viruses use?
They have unusual genetic organization b/c they have compact genomes
They often replicate in the cytoplasm
They have unusual strategies for shutting off host translation and maximizing viral translation
Internal Entry processing
What is polyprotein processing?
- Many viruses produce their proteins as a polyprotein (e.g. Yellow Fever virus, Poliovirus…)
- Allows the virus to produce multiple proteins from a single initiation event
- Polyproteins are cleaved by cellular and/or viral proteases
- Viral proteases are attractive antiviral targets (e.g., HIV, HCV)
What are some ways in which genome replication for DNA viruses can work?
- DNA replication can use cellular mechanisms (JC virus)
- DNA replication can use other mechanisms (Herpesvirus, Adenovirus)
- DNA replication can use cellular enzymes, viral enzymes, or a mixture of cellular and viral enzymes
What are some characteristics of genome replication for RNA Viruses?
- RNA synthesis is usually cytoplasmic
- RNA synthesis is by virally encoded RNA-dependent RNA polymerases
- Replication is through a double-stranded intermediate
- Double-stranded RNA is a key product recognized by the cell as a signature of viral infection through activation of type I interferon, PKR, and RNAseL
- Subgenomic mRNAs are transcribed from some viruses
How does capsid assembly work?
•Capsid assembly usually occurs at the site of genomic replication
•Insertion of the genome into the capsid:
– Packing: pre-formed capsids are “stuffed” with the viral genome (e.g. Herpesviruses)
– Nucleation: capsids form around the genome (e.g. HIV)
•Empty capsids are common
How does envelopement work?
•Envelopment: wrapping a viral capsid in a lipid envelope
•Budding is similar to formation of secretory vesicles –Viral surface proteins are captured by the virus along with cellular lipids
–Can occur at internal membranes (HBV) or at the plasma membrane (HIV)
•Envelopment can occur during or after capsid assembly
What two types of viral release are there? 2 subtypes?
•Lytic release: exit by cellular disintegration
•Non-lytic release: exit without killing the cell – With budding: enveloped viruses – Without budding: non-enveloped viruses or viruses
enveloped at internal membranes
