viruses Flashcards
how do viruses challenge the cell theory?
1 - cells are the smallest unit of life
- viruses lack the necessary molecular machinery to conduct many of the biochemical reactions a normal cell would need
- but viruses contain the genetic material necessary to form the next generation and can evolve in response to the environment
2 - all cells come from pre-existing cells
- viruses can replicate but rely on host cells to provide the energy and materials needed for replicating their genomes and synthesising their proteins
- viruses cannot replicate without entering a suitable host cell
3 - all living organisms are composed of cells
- viruses are acellular and do not have protoplasm or organelles so they are not considered cells
- when in the extracellular virion state, viruses are metabolically inert and don’t carry out respiration or biosynthesis
what structures are present in all viruses?
- genome (comprising DNA/RNA)
- capsid (protein coat) comprising protein subunits, capsomeres
the following structures are NOT present in all viruses
- envelope comprising phospholipids from host cell
- enzymes
describe the viral genome
- viral genomes contain either DNA or RNA, but not both
- viral genomes may be single-stranded, double-stranded, linear or circular
- viral genomes are small, typically encoding functions that the virus cannot adapt from the host
- all viral genomes contain genes coding for essential proteins like respiratory proteins (regulate the action of host genes) and structural proteins (like viral capsid proteins)
describe the capsid (protein coat)
- the capsid encloses the viral genome
- each capsid is constructed from identical protein subunit called capsomeres
- capsomeres are made up of capsid proteins
describe the viral envelope (present in enveloped viruses only)
- the envelope is derived from host cells: when viruses are released from the host cell by budding, they take with them the host’s cell surface membrane (phospholipid bilayer) and insert proteins of viral origins into the membrane
- the proteins include viral glycoproteins that are essential for the attachment of viruses to the next host cell
- the envelope protects the virion’s nucleic acid from the effects of various enzymes and chemicals
viruses that are not surrounded by the lipid membrane envelope are referred to as naked or non-enveloped viruses
what are bacteriophages?
bacteriophages are DNA viruses that infect bacteria
what are 2 examples of bacteriophages?
- T4 phage
- lambda phage
what are structural features of the T4 phage?
genome - linear double-stranded DNA
capsid - capsomeres surrounds the nucleic acid, contained in the phage’s head
tail - consisting of tail sheath, tail fibres and base plate.
tail fibres - allows phage to adsorb onto surface of bacterial cell
tail sheath - surrounds a central tube and enables central tube to pass through host cell wall and membrane
base plate - comes into contact with host cell surface, allowing DNA to enter host cell
what are structural features of the lambda phage?
genome - linear double-stranded DNA
capsid - capsomeres surrounds the nucleic acid, contained in the head of the phage
head - the 5’ terminus of each DNA strand is a single-stranded tail that is 12 nucleotides long, which is important in prophage formation
single tail fibre - allows phage to adsorb onto the surface of the bacterial cell by binding to the specific receptor found on the cell surface
lambda phages’ tails are NOT CONTRACTILE and serves to deliver the viral DNA to the cell membrane
define lytic cycle and lysogenic cycle
lytic cycle: a phage reproductive cycle that finally results in the death of the host cell
lysogenic cycle: involves replication of the phage genome without destroying the host in the initial steps.
VIRULENT phages (eg T4 phage) reproduce through the lytic cycle
TEMPERATE phages (eg lambda phage) reproduce through the lysogenic cycle)
true or false: the T4 phage reproduces through the lytic cycle
TRUE
T4 phage, a virulent phage, reproduces using the LYTIC CYCLE
lytic or lysogenic?
which reproductive cycle does the lambda phage use to reproduce?
lysogenic.
lambda phage, a temperate phage, reproduces through the lysogenic cycle.
APSAR
what are the 5 step of the lytic cycle?
- adsorption
- penetration
- synthesis (of phage proteins) & replication (of phage nucleic acid)
- assembly
- release
using the T4 phage as an example, describe, in detail, the lytic cycle.
step 1: adsorption
- T4 phage’s multiple tail fibres attach to specific receptor sites on the surface of a bacterial host cell
- the base plate settles down on the host cell surface
step 2: penetration
- conformational changes occur in the tail sheath, causing it to contract and its tube pierces through the bacterial cell wall and cell membrane
- T4 uses lysozyme to hydrolyse peptidoglycan, degrading a portion of the bacterial cell wall for insertion of the tail core
- DNA is extruded from the head, through the tail tube, into the host cell
- the capsid is left on the outside of the bacterial cell wall
step 3: synthesis & replication
- after phage DNA is injected into the host cell, synthesis of host DNA, RNA and proteins is halted. the host cell machinery is taken over by the virus for synthesis of viral nucleic acids and viral proteins
- host DNA is degraded into nucleotides, providing raw materials for T4 phage DNA replication by host DNA polymerase
- T4 phage mRNAs are synthesised by host RNA polymerases through transcription
- T4 phage mRNAs are translated by host cell ribosomes, tRNAs and translation factors into viral proteins and enzymes required to take over the host cell and replicate phage nucleic acids.
step 4: assembly
- viral proteins are assembled to form phage heads, tails and tail fibres
- these components are assembled into the complete bacteriophage
step 5: release
- the T4 phages LYSE the host cell using the lysozyme, which digests the bacterial cell wall
- water enters the cell by osmosis, causing it to swell and burst
- lysozyme (an enzyme) makes a small hole in the bacterial cell wall, allowing the viral nucleic acid to enter
- proteins translated from T4 phage mRNAs include enzymes for viral replication and inhibitory factors that stop host cell RNA and protein synthesis
APPS
what are the 4 steps of the lysogenic cycle?
- adsorption
- penetration
- prophage formation
- switch to lytic cycle
using the lambda phage as an example, describe, in detail, the lysogenic cycle.
step 1: adsorption
- the single tail fibre of the lambda phage attaches to a specific receptor site on the surface of a bacterial host cell
- the base plate settles down on the host’s cell surface
step 2: penetration
- DNA is extruded from the head, through the tail tube and injected into the host cell, passing through the bacterial cell wall and cell membrane
- the capsid is left on the outside of the bacterial cell wall
step 3: prophage formation
- the lambda phage genome circularises & inserts itself into a specific site on the bacterial chromosome (prophage insertion site) by genetic recombination. there is NO LOSS of host DNA.
- the integrated lambda phage is known as a prophage
- in the integrated state, the viral DNA is replicated along with the chromosome each time the host cell divides, and is passed on to generations of the host daughter cells
- a single infected cell can soon give rise to a large population of bacteria carrying the viral DNA in prophage form
step 4: switch to lytic cycle
- when there is an environmental trigger (eg UV radiation) the virus switches from the lysogenic cycle to the lytic cycle
- lysis genes which were repressed during lysogeny are activated, allowing the lambda phage genome to be excised from the bacterial chromosome, giving rise to new active phages
- steps 3-5 (synthesis and replication, assembly, release) of the lytic cycle resumes
lambda phages’ tails are NOT CONTRACTILE and serves todeliver the viral DNA to the cell membrane
what are enveloped animal viruses and state two examples of it.
enveloped animal viruses are viruses with a membranous envelope surrounding their nucleocapsids.
examples of enveloped animal viruses include the influenza virus and human immunodeficiency virus (HIV)
what is the influenza virus?
- the influenza virus is an enveloped virus in which the viral negative (-) sense single-stranded RNA is present in the virion in 8 separate pieces.
- the negative (-) sense viral RNAs must first be transcribed to positive (+) sense single-stranded RNA which serves as mRNA for translation
- (-) sense single-stranded RNA is subsequently synthesised from (+) sense single-stranded RNA for use as genomic material and packaged with the viral proteins to form new virions
what are structural features of the influenza virus?
genome - 8 different segments of negative (-) sense single-strand RNA. (-) sense RNA must be transcribed to complementary (+) sense RNA before it can be used for translation of viral proteins
capsid - nucleoprotein (NP) associate with the viral nucleic acid to form nucleocapsid
membrane/viral envelope - phospholipid bilayer obtained from host cell surface membrane upon budding
surface glycoproteins - haemagglutinin (HA) and neuraminidase (NA)
protein envelope - matrix protein (M1 & M2) forms second layer of envelope, enclosing the nucleocapsid
enzymes - PB1, PB2 & PA forms RNA-dependent RNA polymerase (replicase), NS1 regulates viral replication mechanisms
details of protein envelope & enzymes dn memo
haemagglutinin - binds to sialic acid containing receptors, attaching virus to receptor on host cell membrane
neuraminidase - hydrolyses mucus, allowing virus to entercells of the respiratory tract & facilitates budding by cleaving sialic acid containing receptors
APSAR
what are the 5 steps of the reproductive cycle of influenza virus?
- adsorption
- penetration
- synthesis (of viral components) and replication (of viral genome)
- assembly of new virion
- release
describe, in detail, the reproductive cycle of influenza virus
step 1: adsorption
- haemagglutinin (HA) molecules on the viral membrane binds to sialic acid containing receptors on the membrane of the host cell (epithelial cells of the respiratory tract)
- (HA molecules have a complementary 3D shape with the receptor)
step 2: penetration
- the virus is taken in by receptor-mediated endocytosis, forming an endocytic vesicle within the host cell, aka endosome, with the influenza virus attached to its inner surface
- fusion of the endosome with an acidic lysosome lowers the pH of the vesicle, triggering conformational changes in the HA protein, causing the viral envelope and endosome membranes to fuse, releasing the 8 viral segments of the influenza genome directly into the host cell cytoplasm.
- viral RNAs are transported into the nucleus
step 3: synthesis & replication
- viral replicase (incuded as part of the virion) copies the (-) sense RNA template into complementary (+) sense RNAs for synthesis of viral nucleic acids and viral proteins.
- (+) sense RNAs are used as templates for synthesis of full length (-) sense strand viral RNAs by viral replicase. the (-) sense viral RNAs can be packaged into new viral particles as their nucleic acid
- (+) sense RNAs are used as mRNA which are translated in the cytoplasms by host ribosomes, synthesising enzymes, matrix proteins capsomere proteins and glycoproteins.
- free ribosomes synthesise enyzmes, matrix and capsomeres as they are ultimately folded into final conformation in the cytoplasm and packaged into the new virion. rER-bound ribosomes synthesise viral transmembrane surface glycoproteins, which are transported to the golgi apparatus for glycosylation before being incorporated into the host cell membrane via a vesicle which fuses with the host cell membrane
step 4: assembly
- 8 (-) sense viral RNAs associate with nucleoprotein (NP), and enzymes (eg viral replicase) are packaged, completely assembling viral particle.
- the glycoprotein studded membran envelope is acquired during the release of the virus
step 5: release
- the virus is released from the host cell by budding, acquiring the host cell’s lipid bilayer as the virus’ envelope
- the host membrane containing HA, NA and M2 (matrix protein) buds off from the host cell with the virion components
- because HA is present on the viral envelope and sialic-containing cellular receptors are on the host cell’s membrane, budding brings the virus and host cell together, resulting in the new viral particle remaining attached to the host cell
- neuraminidase (NA), helps release the virus by cleaving sialic acid residues on the cellular receptor that binded the newly formed virions to the cell
- this releases the virions, allowing infection to continue
virion: new virus that is synthesised
what is human immunodeficiency virus (HIV)?
HIV (human immunodeficiency virus) is a retrovirus that causes AIDS (acquired immunodeficiency syndrome)
a retrovirus is an enveloped RNA virus which replicates by means of a DNA intermediate synthesised by the enzyme reverse transcriptase
what are structural features of HIV?
genome - 2 identical single-stranded RNA. the single-stranded RNA is reverse transcribed to produce DNA for integration into the host genome. the DNA is then used for the transcription of viral mRNA which is translated into viral proteins and for use as the viral genome in the progeny virus
capsid - surrounds the nucleic acid
viral envelope - is the phospholipid bilayer obtained from the host cell upon budding
surface glycoproteins - gp120 (binds to CD4 receptors on WBCs like macrophages & T helper cells) and gp41 (helps HIV envelope & host cell membrane fuse)
protein coat - made of matrix protein, forming the 2nd layer of the protein envelope and enclosing the capsid
enzymes - reverse transcriptase (reverse transcribes RNA into DNA), integrase (facilitates incorporation of double-stranded DNA into host cell’s genome) and protease (cleaves viral polypeptide into functional proteins)
APSAR
what are the 5 steps of the reproductive cycle of HIV?
- adsorption/attachment
- penetration
- synthesis (of viral components) & replication (of viral genome)
- assembly of new virions
- release
describe, in detail, the reproductive cycle of HIV
step 1: adsorption/attachment
- glycoprotein gp120 on the surface of HIV binds to the CD4 receptor, found on T helper cells and macrophages of the host immune system
step 2: penetration
- upon binding to CD4, gp120 undergoes a conformational change, allowing it to bind to a co-receptor, CXCR4 on T helper cells and CCR5 on macrophages
- gp41 pulls the virus closer to the host cell. the co-receptor facilitates the entry of the gp120-CD4 complex through the host cell membrane
- the HIV envelope fuses with the host cell membrane, releasing the viral contents consisting of viral nucleic acid and enzymes into the host cell
step 3: synthesis & replication
- reverse transcriptase reverse transcribes the viral RNA into a complementary DNA strand. the RNA strand of the DNA-RNA is broken down by the ribonuclease H component of the reverse transcriptase, and the newly syntesised DNA strand is used as a template for synthesis of the other complementary DNA strand, forming a double-stranded DNA molecule
- this DNA molecule then passes through the nuclear pore, entering the host nucleus
- integrase catalyses the integration of the viral DNA into the genetic material of the host
- the newly integrated viral DNA is called a provirus, which remains latent (inactive) until the host cell is stimulated in an immune response
- when the host cell receives a signal, the proviral DNA is transcribed by host RNA polymerase into RNA
- proviral DNA is also transcribed into viral mRNA, which is then translated to produce a single long chain of HIV proteins which is later cleaved. viral proteins include enzymes, matrix & capsomeres proteins, glycoproteins
- viral surface glycoproteins are synthesised by rER-bound ribosomes and transported to the golgi apparatus for glycosylation and then incorporated into the host cell membrane via vesicles which fuses with the host cell membrane
step 4: assembly of new virions
- copies of HIV proteins and HIV’s RNA genome assemble near the host cell membrane to form a new virus particle
- assembly of the viral components occur when the viral components of 2 single-stranded RNA molecules associate with reverse transcriptase, and enzymes like integrase and protease are surrounded by assembled capsid.
step 5: release
- the glycoprotein studded membrane envelope is acquired during the release of the virus
- the newly assembled immature HIV buds off from the host cell, surrounded by the host membrane
- viral maturation occurs when the HIV protease cleaves the single long chains of HIV proteins into smaller functional proteins, forming a mature HIV particle
what are the 3 mechanisms for variation in viral genomes?
1 - mutation
- no proofreading mechanisms in host cell → RNA viruses have higher rates of mutation as errors are not corrected.
- enzymes like reverse transcriptase (HIV) also has very low fidelity → regularly introduce errors into the genome
- responsible for antigenic drift
2 - recombination
- viruses may undergo recombination with the genome of another strain → exchange of genetic information → new combinations of alleles
3 - reassortment
- a host cell may be infected with 2 viral strains, introducing two sets of genetic material into the host cell → different segments of the viral genome may be packaged into the progeny virus when it is being formed → sudden and drastic change in the viral genome → antigenic shift
what is an antigen?
an antigen is any substance that can be recognized by the immune system. it is a molecule that binds to an antibody or a T-cell receptor (TCR) which elicits a B cell or T cell response respectively
antigenicity is the capacity of an antigen to induce an immune response in a host
antigenic shift & antigenic drift results in the formation of new antigens, changing the antigenicity of the virus and are essential in mediating their ability to evade host defence mechanisms
define antigenic shift
antigenic shift is a sudden change in the antigenicity of a virus owing to reassortment of the segmented virus genome with another genome of a different antigenic type
in the influenza virus, antigenic shift results in new haemagglutinin (and sometimes new neuraminidase) proteins in the viruses that infect humans.
antigenic shift results in new influenza A subtype or a virus that has emerged from an animal population that is so differen from the same subtype in humans that most people do not have immunity to the new virus.
using influenza as an example, describe the mechanism of antigenic shift
- antigenic shift arises when different influenza A strains infect a host and subsequently forms progeny viruses whose genome is a new combination of RNA from the different strains
- the influenza virus, containing 8 single-stranded RNA is susceptible to such reassortment as it can easily reshuffle its genome during the packaging of the new virion
- different viruses of different origins may infect a pig, providing the opportunity for the viruses to reassort, forming a new virus which contains different surfaces antigens from both the avian and human influenza strain
- forms viruses with new combinations of haemagglutinin and neuraminidase → new strain of influenza would not have been circulating in the population → not likely be any immunity against this novel strain, and the new virus is easily transmissible
define antigenic drift
antigenic drift is the gradual accumulation of minor mutations in the genes of influenza viruses that results in altered antigenicity
antigenic drift happens continually over time in the genes of viruses like the influenza virus as the virus replicates → results in small changes which produce viruses that are closely related to each other and usually share the same antigenic properties
describe the mechanism of antigenic drift.
antigenic drift arises when viruses undergo continuous, subtle antigenic changes due to accumulation of mutations to the haemagglutinin and/or neuraminidase genes
factors that influence the rate of mutation of viral genomes:
- as the influenza genome consists of 8 single-stranded RNA strands which lack a complementary strand, mismatch repair cannot be carried out
- viral polymerases are prone to errors and will introduce mutations during DNA replications (as RNA polymerase does not have proofreading ability)
- HIV encodes an average of 1 point mutation for every replication cycle as viral reverse transcriptase is unable to correct nucleotide misincorporation errors
these mutations result in the production of surface proteins with different 3D conformations, resulting in antibodies no longer being complementary to them and will not recognise and bind to them
compare the differences between antigenic shift and antigenic drift
no. of viruses
- antigenic shift: 2 or more viral strains involved
- antigenic drift: only 1 viral strain involved
mechanism for change
- antigenic shift: reshuffling of genome between different strains, resulting in dramatic alteration of type of haemagglutinin or neuraminidase on progeny virus
- antigenic drift: accumulation of point mutations in the gene of the surface antigen, resulting in minor alteration of 3D conformation of haemagglutinin or neuraminidase on progeny virus
nature of change
- antigenic shift: abrupt & major change in genome of virus
- antigenic drift: gradual accumulation of minor point mutations in genome of virus
rate of occurrence
- antigenic shift: occasionally occurs, giving rise to pandemics
- antigenic drift: regularly occurring, giving rise to seasonal epidemics
effect of host immunity
- antigenic shift: population has no immunity to novel combination of surface proteins, and no drugs or vaccines are present to treat the virus
- antigenic drift: a proportion of the population may have pre-existing immunity to the modified surface proteins, and anti-viral drugs and seasonal vaccines are available to treat the virus
cross-species transmission
- antigenic shift: may result in a progeny virus which can infect a new species
- antigenic drift: only infects individuals of the same species
what are the effects of antigenic shift and antigenic drift?
- ANTIGENIC SHIFT & DRIFT. viruses mutate & change the antigens on their surfaces → prevents antibodies from recognising them → allows viruses to evade detection by the host immune system.
- ANTIGENIC SHIFT & DRIFT. vaccines would become ineffective as antibodies generated would be unable to bind specifically to the new surface antigen which has a new and different 3D conformation → virus can evade the host’s immune system and continue its reproductive cycle.
- ANTIGENIC SHIFT. major change in surface proteins causes a large number of people being susceptible to the new virus, causing a pandemic. ANTIGENIC DRIFT. gradual & minor change in surface proteins allows some people to be unaffected due to pre-existing immunity, causing a seasonal epidemic.
