Lecture 6 Virus Flashcards
Key concepts
➢ A virus consists of a nucleic acid
surrounded by a protein coat
➢ Viruses replicate only in host cells
➢ Viruses and prions are formidable
pathogens in animals and plants
A Glimpse of History in tobacco
▪ Tobacco mosaic disease (1890s)
* D. M. Iwanowsky, Martinus Beijerinck determined caused
by “filterable virus” too small to be seen with light
microscope, passed through filters for bacteria
* F. W. Twort and F. d’Herelle discovered “filterable virus”
that destroyed bacteria
* Virus means “poison”
Viruses: Obligate Intracellular Parasites
▪ Genetic information: DNA or RNA contained within
protein protective coat
* Inert particles: no metabolism, replication, motility
* Genome hijacks host cell’s replication machinery
* Inert outside cells; inside, direct activities of cell
* Infectious agents, not organisms
* Can classify generally based on type of cell they infect:
eukaryotic or prokaryotic
- General Characteristics of Viruses
Virion (viral particle) is nucleic acid, protein coat
* Protein coat is capsid: protects nucleic acids
○ Carries required enzymes
○ Composed of identical subunits called capsomeres
* Nucleocapsid = NA + capsid
* Matrix protein between nucleocapsid and envelope
* Enveloped viruses have lipid bilayer envelope
* Non-enveloped (naked) viruses lack envelope; more resistant to disinfectants
virus size/ shape
slide 6
Viral Structure
▪ Viral genome is either DNA or RNA, never both
* Useful for classification (that is, DNA or RNA viruses)
* Genome linear or circular
* Double- or single-stranded
▪ Viruses have protein components for attachment
* Phages have tail fibers
* Many animal viruses have spikes
* Allow virion to attach to specific receptor sites
Viral Shape
▪ Generally four different shapes
* Icosahedral (Adenovirus)
* Helical or rod (TMV)
* Complex (bacteriophages like T2)
* Spherical (influenza, coronavirus)
slide 8
- Replicative cycle
Generally four steps
* Attachment and Entry
* Synthesis
* Assembly of particles
* Exit of the cell
slide 9
Replication of Bacteriophages and the types of relationships
▪ Viruses that infect bacteria
▪ 3 general types of bacteriophages based on relationship
with host
* Lytic phages
* Temperate phages
* Filamentous phages
Lytic Phage Infections
● Lytic or virulent phages exit host
● Cell is lysed
○ Productive infection: new particles formed
● T4 phage (dsDNA) as model; entire process ~30 min
● Five step process
○ Attachment
○ Genome entry
○ Synthesis
○ Assembly
○ Release
Lytic Cycle
slide 12
Lytic Cycle (time lapse)
slide 13
Lysogenic Cycle
slide 14
Bacterial Defenses Against Phages
- Preventing Phage Attachment (NO RECEPTORS)
- Restriction enzymes (restrict a phage’s ability to replicate
within the bacterium - CRISPR-Cas system
- Preventing Phage Attachment
Alter or cover specific receptors on cell surface
* May have other benefits to bacteria
* S. aureus produces protein A, which masks phage receptors;
also protects against certain human host defenses
* Capsules, slime layers (biofilms) also mask receptor
- Restriction-Modification Systems: two enzymes
Restriction enzymes (RE)
● Restrict a phage’s ability to replicate within the bacterium
● Recognize, cut short nucleotide sequences (phage DNA)
● Bacteria have different versions; hundreds of varieties
slide 19
- Restriction-Modification Systems: two enzymes
Methylase
Methylate host sequences normally recognized by RE
* Restriction enzymes do not recognize bacterial DNA
* Enzymes methylate (CH3) bacterial DNA
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3.CRISPR-Cas system
- Bacterial immune system
- CRISPR - clustered regularly interspaced short palindromic repeats
- Cas (CRISPR-associated protein) degrades RNA
slide 21
Replication of Animal viruses
Key Characteristics of animal viruses
● Genome structure
- Nucleic acid (RNA or DNA)
- Strandedness: single-strand(ss) or double-strand (ds)
● Enveloped vs non enveloped
● Hosts infected
● Other characteristics
- viral shape
- disease symptoms
Central dogma of Biology
slide 23
think of what should the host provide and what should the virus provide
Baltimore classification System of Viruses
slide 24-26
+ strand used as a template
Synthesis of viral genetic material
● Expression of viral genes to produce viral structural and
catalytic genes (for example, capsid proteins, enzymes
required for replication)
● Synthesis of multiple copies of genome
● Most DNA viruses multiply in nucleus
● Enter through nuclear pores following penetration
● Three general replication strategies depending on type of
genome of virus
○ DNA viruses ( Herpes, Pox, HPV)
○ RNA viruses (Flu, Covid)
○ Reverse transcribing viruses (Retroviruses)-HIV
Sense vs nonsense review
slide 28
What is Antisense RNA
Antisense RNA is a single-stranded RNA that is complementary to the messenger RNA (mRNA) strand transcribed within a cell
they are introduced in a cell to inhibit the translation machinery by base pairing with the sense RNA and activating the RNase H, to develop a particular novel transgenic
mRNA = Sense
slide 29
Different polymerases
DNA-dependent DNA polymerases
- eg. prokaryotic and eukaryotic DNA polymersases
DNA-dependent RNA polymerase
- eg. RNA polymerases and DNA primase’
RNA-dependent DNA polymerase
-eg. reverse transcriptase
RNA-dependent RNA polymerases
-eg. RNA replicase
Replication of DNA viruses
Usually in nucleus
* dsDNA replication straightforward
* ssDNA similar except complement first synthesized
slide 31
Replication of RNA viruses
- Majority single-stranded; replicate in cytoplasm
- Require virally encoded RNA polymerase (replicase), which lacks
proofreading, allows antigenic drift (influenza viruses) - ss (+) RNA used as mRNA
- ss (–) RNA, dsRNA viruses
carry replicase to synthesize (+) strand - Some RNA viruses segmented;
Reassortment results in antigenic shift
Polymerases used
RNA polymerase-RNA dependent = Replicase
slide 32
Replicative cycle of an enveloped RNA virus.
slide 33
Replication of reverse-transcribing viruses
- Encode reverse transcriptase: makes DNA from RNA
- Retroviruses have ss (+) RNA genome (HIV)
- Reverse transcriptase synthesizes single DNA strand
- Complementary strand synthesized; dsDNA integrated into host cell
chromosome - Can direct productive infection or remain latent
- Cannot be eliminated
Polymerases used
DNA polymerase –RNA dependent =
reverse transcriptase
RNA polymerase-DNA dependent
DNA polymerase –DNA dependent
The replicative cycle of HIV
3 genes in common: gag, pol, and env
* gag gene - viral protein coat
* pol gene - reverse transcriptase and
integrase (inserts the viral DNA into a host
chromosome)
* env gene - glycoproteins that appear
on the surface of the viral envelope
* reverse transcriptase is very error
prone – high mutation rate (evolve
rapidly)
Human Immunodeficiency Virus (HIV)
- AIDS caused by HIV-1 and HIV-2
- HIV-1 evolved from a similar virus SIV
cpz
simian
immunodeficiency virus found in chimpanzees
and was transmitted to humans. - SIV
cpz
arose from recombination between
retroviruses from red-capped mangabeys and
from greater spot-nosed monkeys - Independent transfers of SIVcpz to humans gave
rise to different groups (strains) of HIV-1
Why do new viruses emerge?
- Mutation of existing viruses into new viruses
- Spread due to affordable international travel
- Spread of existing viruses from other animals
Influenza
● 36,000 death/year
● Structure: 8 sense viral RNA and two surface antigens
● Rapid changes occur through genetic recombination.
● Three main types:
○ Influenza A
○ Influenza B
○ Influenza C
● Cases influenza A: divided into subtypes based upon
expression of hemagglutinin (HA) and
neuraminidase (NA).
slide 37-38
Coronaviruses
- Spherical or
pleomorphic
enveloped particles
containing - single-stranded
(positive-sense) RNA
associated with a - nucleoprotein within a
capsid composed of
matrix protein. - envelope bears
club-shaped
glycoprotein
projection - glycoprotein spike on
the surface, which
mediates receptor
binding and cell entry
during infection
slide 39
Prions: Proteins as Infectious Agents
▪ Prions are proteinaceous infectious agents
* Composed solely of protein; no nucleic acids
* Linked to slow, fatal human diseases; animal diseases
* Usually transmissible only within species
* Mad cow disease in England
* Creutzfeldt-Jakob disease in humans killed 175 people
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Creutzfeldt-Jakob disease
slide 41
Spongiform encephalopathies
Prion proteins accumulate in neural tissue
* Neurons die
* Tissues develop holes
* Brain function deteriorates
Characteristic appearance
gives rise to general term for all prion diseases: transmissible
spongiform encephalopathies
