Essentials of Virology Flashcards
What is a virus?
An infective agent that typically consists of a nucleic acid molecule in a protein coat, is too small to be seen by a light microscope and is able to multiply only within the living cells of a host
- 320,000 that can infect mammals but constantly changing
- referred to as obligate intracellular parasites
Four(ish) viral hosts
- Humans
- Animals (and insects hence the ish)
- Plants
- Bacteria
Describe what a virus’s host range is, and how a virus can be transmitted.
Where a virus is found can be described as its ‘host range’.
Importantly, some viruses can move between hosts e.g between humans and animals.
Viruses can be found in reservoirs or amplifying hosts. These are organisms in which the virus exists, but doesn’t necessarily cause disease.
- 3 major categories of reservoir hosts are avians, swine and rhodentia
Viruses are transmitted via vectors, such as flies and ticks. These vectors can either infect humans or incident/dead-end hosts. They’re called dead-end because the virus cannot spread to humans from them. The vectors cannot be infected due to complexity of the insect’s immune system.
Between humans, we have horizontal (from mother to child i.e between same species, through blood, saliva, sexual contact, airborne) transmission and vertical (from human to human via contact/ air, etc.) transmission.
Virus may spread to adjacent cells extracellularly or intracellularly. Extracellular
spread occurs by release of virus into the extracellular fluid and subsequent
infection of the adjacent cell. Intracellular spread occurs by fusion of infected cells
with adjacent, uninfected cells or by way of cytoplasmic bridges between cells.
In what tissues and organs can viruses be found?
Viruses can be found in multiple tissues and organs of their host. The tissues that viruses can be found in are referred to as their ‘tissue tropism’.
Through the process of evolution, viruses evolve to replicate in tissues that favour transmission between hosts (eg. replicate in lungs, transmitted in air) and allow them to evade the immune system of the host (eg. replicate in cells of immune system, preventing immune function).
Enter cells by direct fusion or endocytosis
Move inside cells using intracellular structures
Exit cells using budding or lysis
How do viruses cause disease?
Suggest why antibiotics are not prescribed for viral infections
Viruses can cause a range of diseases, either directly (as a product of their host range) or indirectly (by inhibiting cell function). The diseases can be respiratory, immunodeficiency and cancer related.
The disease can be acute (severe and sudden onset) or chronic (long-developing).
Have cytocidal effects
- Have morphological, genotoxic effects with effects on the cell’s biochemistry and physiology
Have persistent effects (i.e latent/chronic infections)
Can transform
- Gains the capacity for unlimited cell division (immortalization), and the immortalized cells acquire additional genetic changes to produce a tumor.
- the tumor virus may introduce and express a stransforming gene in the cells
- the tumor virus may alter the expression and (or) coding capacity of preexisting cellular genes. After development of a malignant phenotype the relevant segment(s) of the viral genome may or may not be retained in the transformed cells, depending on the mechanism of transformation. These mechanisms are not mutually exclusive, and both may occur in the same cell.
Generally antibiotics target cell wall synthesis and viruses dont have a cell wall
List some key differences between bacteria, prions and viruses.
BACTERIA:
- contain nucleic acid (DNA) covered in protein
- have a cell wall (composed of sugar molecules)
- can replicate outside of the cell
PRIONS:
- are proteins
- do not contain nucleic acid
- replicate inside the cell
VIRUSES:
- are nucleic acid (DNA or RNA) covered in proteins
- have no cell wall, may or may not have a lipid coat
- mus replicate inside the cell
What are the essential structural features of a virus?
- must contain nucleic acid (DNA or RNA)
- covered in a protein coat (as a capsomere or capsid)
Different viruses have different structures, but retain similar organisation.
Virus structure can dictate host range and tissue tropism.
Describe the essential features of virus replication.
VIRUS WITH DNA:
A virus will enter the cell and uncoat its DNA. The genome then transcribes this DNA to produce new capsid proteins. At the same time, the viral DNA is being replicated.
There is then the self-assembly of new virus particles and their exit from the cell, either by budding off or lysis of the host cell.
(Depending on the independent strategies of the virus, the genome will go to specific compartments in the cell to replicate. This compartment will dictate what the virus can access. Viruses must replicate inside these to use these specific cell factors.)
VIRUS WITH RNA:
The essential features of the replication are quite similar.
In this scenario, the capsid makes it into the cell. the capsid can recognise proteins in the cell, so it can direct the virus to its designated compartment.
Once again, there is the production of the viral genome proteins for the new capsids, and the replication of the viral genome.
Then, there is the self-assembly of the new viruses and their exit from the cell.
5 GENERAL STEPS
- Entry into the cell - direct fusion or endocytosis - using attachment/entry receptors present on exterior of virus. Interact with receptors on cell surface. Envelope/spike protein interactions mediate entry to cell.
- Genome movement - using intracellular structures. Capsid protects viral nucleic acid in and out of the cell. Capsid can dictate virus movement within the cell during entry. Capsid expressed from the viral genome assembles around nucleic acid during
virus assembly and egress - genome replication. Uses polymerases. Polymerase proteins are not found in viruses (ie not carried into the cell) but are proteins expressed by the viral genome.
- Genome packaging into protein shells. During virus assembly cellular proteins move individual viral proteins between compartments (ie nucleus to cytoplasm, or nuclear membrane to plasma membrane) – excretory pathway. During virus assembly cellular proteins move structures containing viral proteins between compartments (ie nucleus to cytoplasm, or nuclear membrane to plasma membrane) – cellular cargo mechanisms.
- Exit from the cell through budding or lysis. During virus exit (egress) cellular proteins move individual virus through the plasma membrane – cellular egress proteins. Movement of virus through the plasma membrane while membrane intact is
virus budding. Movement of virus through the plasma membrane, which dissolves membrane, is virus lysis.Movement of virus through the plasma membrane can cause damage and cell death.
What are the four different configurations of the viral genome? Describe their structures.
- single-stranded RNA (ssRNA)
- double-stranded RNA (dsRNA)
- single-stranded DNA (ssDNA)
- double-stranded DNA (ddDNA)
Based on this, we can separate viruses into different families.
Baltimore classification
- Genomes classified depending on what their genetic material looks like
- double-stranded genomes have complementary base pairing
- RNA genomes can be linear and segmented (ie. more than one RNA per capsid)
- DNA genomes can be linear or circular
Genomes can encode information (genes) in a positive or negative sense, 5’-3’ or 3’-5’ respectively. For negative sense, RNA polymerase then reads the RNA and makes a complementary strand in the opposite direction
How do viruses use the Central Dogma to replicate?
DNA VIRUSES:
They use DNA Polymerase to simply follow through the Central Dogma and express their proteins.
RNA VIRUSES:
If they have negative sense RNA, they depend on RNA Polymerase, which can simply read off other copies of the RNA genome, regardless of the sense of the strand (positive or negative). This transcribes a positive strand, which can be sent through the Central Dogma to create proteins.
Retroviruses subvert this dogma - mediated by reverse transcriptase
Give two examples of proteins that viruses can produce.
POLYMERASE:
Polymerase proteins are enzymes that are involved in the catalysis of nucleotides to nucleic acids.
Viruses with DNA genomes produce DNA polymerases, while viruses with RNA genomes produce RNA polymerases.
Polymerase proteins interact with nucleic acids in protein-nucleic acid interactions.
STRUCTURAL PROTEINS:
These are proteins that form the capsid into which nucleic acid is packed.
These proteins interact with one another in protein-protein interactions.
How do viral proteins promote pathogenesis?
Suggest how pathogenesis can cause cancer. Give some examples of some viruses that can cause cancer, and describe how this could happen.
As ‘obligate cellular parasites’, viral and cellular proteins shape the intracellular environment to facilitate viral replication, or evasion of an immune response.
Commonly, changes to the intracellular environment that facilitates virus replication or evasion of an immune response lead to disease (pathogenesis).
As cells divide, they go through the cell cycle. During the cell cycle, the cell produces factors that a virus might need. An example of this is the production of nucleotides that can be used by viral polymerases to make new viral genomes.
Some viruses produce proteins that ensure that the cell continuously goes through the cell cycle and so subvert the checkpoint proteins.
Cancer can be defined as an uncontrolled cell division. Thus, viruses can cause cancer by causing uncontrolled cell division that benefits their replication.
EXAMPLES
- Human Papilloma viruses (HPVs) - Papilloma virus, circular dsDNA genome, skin cancer
- Hepatitis B virus (HBV) - Hepadnavirus, circular dsDNA genome, carcinoma
- Hepatitis C virus (HCV) - Flavivirus, ssRNA genome, carcinoma
- Human Immunodeficiency virus (HIV)
Human Papillomavirus (HPV) proteins E6 and E7 remove the ‘brakes’ i.e checkpoint proteins of the cell cycle.
E6 can remove/degrade p53, an important factor that halts the cell cycle, so it allows the cell cycle to go on.
E7 binds to RB, preventing it from binding to E2F, once again allowing the cell cycle to go on.
How can virus pathogenesis lead to immunodeficiency?
Suggest how HIV causes immunodeficiency.
Viruses must evade immune responses. Some immune responses are mediated by specific cells of the immune system. these immune cells recognise and kill cells infected by a virus.
To evade this type of immune response, some viruses replicate in the immune system cells whose functions is to recognise and kill infected cells.
Replication in immune cells hides the virus from the immune cells and inhibits immune cell functions.
Inhibition of immune cell function allows other pathogens to replicate in virus-infected hosts and, thus, disease occurs.
HIV:
In an uninfected person, the thymus produced normal CD4 cells, some of which will die of apoptosis (natural occurrence, as it keeps all of the cells being replenished).
In an infected person, some of the CD4 cells made by the thymus will be infected, and these, in turn, will cause a number of different molecular pathways to be activated, all of which cause cell death.
List some HIV-associated pathogens.
VIRUSES:
- Kaposki’s sarcoma hepesvirus (KSHV) - cancer-causing
- Herpes simplex virus (HSV)
BACTERIA:
- Mycobacterium tubercolosis
- Salmonella
FUNGUS:
- Candida
- Cryptococcus neoformans
PARASITE:
- Cryptosporidium
- Toxoplasma gondii
Mostly, hosts never really die of the HIV; it simply facilitates the entry of other pathogens which then kill the host (i.e opportunistic infections)
