Virology Flashcards
Define a virus and explain some of the structures that they do and don’t possess
A virus is an obligate parasite with no metabolic processes
For example:
- viruses do not encode genes for mitochondria therefore they steal energy (ATP) from the cell
- viruses do not encode ribosomal genes thus bacterial ribosomes are common antibiotic targets ^[as the morphology differs, this provides a potentially wide therapeutic window]
- viruses cannot create structures like the ER and Golgi
- envelopes — if they have it —come from the cell
> the bacterial cell wall is a common target for antibiotics. Therefore if it has an envelope you can’t drug it
Define and distinguish the following terms: virion or viral particel, capsid, infectious unit, specific infectivity
- virion or viral particle: the physical structure that is transmitted. In a way, the virion is ‘functionally dead’ while being transmitted. On electron microscopy the virion appears complete.
- capsid: a protein shell that surrounds a virus genome in the virion
- infectious unit: the amount of virus required to cause infection
>can depend on the host
>a single virion is (probably) never an infectious unit
n.b. this is difficult to define, to decide how to define - specific infectivity: the ratio of virions to infectious units
> virions are degrees of magnitude greater then in infectious units in number, many duds are generated in the process of replication
> e.g. Mpox generates airborne virions, but they are not the infectious unit i.e. must be transmitted with skin to skin contact
Compare and contrast infectious unit and specific infectivity
- infectious unit: the amount of virus required to cause infection
>can depend on the host
>a single virion is (probably) never an infectious unit
n.b. this is difficult to define, to decide how to define - specific infectivity: the ratio of virions to infectious units
> virions are degrees of magnitude greater then in infectious units in number, many duds are generated in the process of replication
> e.g. Mpox generates airborne virions, but they are not the infectious unit i.e. must be transmitted with skin to skin contact
Briefly describe the host requirements of various viruses
host requirements vary
> - some have narrow host specificity e.g. measles which essentially solely infect humans
> - some have broad host specificity e.g. cowpox and mammals
> - some require multiple host species e.g. RRV needing both mosquitoes and humans. may be vertebrates or invertebrates
Briefly describe how viruses are classified
Classical tools that are used to classify viruses include nucleic acid type, genome architecture i.e. whether linear, circular or segmented, symmetry of capsid, presence of envelope or enzymes, antibody cross-reactivity (serology), and Baltimore classification
- families
More recently, the genome sequence is being used. This looks at the position of sequence features and gene order, and the relatedness of genes/phylogenetics.
Note that similarity in protein structure, even when gene structures are different.
Explain the variety of genome architecture in viruses
Essentially the principle of genome architecture when it comes to viruses is simply, anything goes. Genomes can be DNA or RNA, single stranded or double stranded, positive^[can be translated by ribosomes directly, see [[Genetics]]] and negative sense, segmented, linear etc.
The virus capsid morphology can also vary. It can take the stereotypical icosahedral shape or it can be helical as in the case with rabies.
Additionally, viruses can be encapsulated or enveloped in a lipid membrane, stolen from the cell, decorated with sugars ^[a means to avoid immune detection]; or not– these viruses are said to be naked.
Explain the common features involved in virus replication in cells
The basic textbook view of virus replication is that the virus enters the cells, synthesises proteins required to then synthesise the genome, then assembly of the viral particle and its release.
The question is, is it ever that simple? While, yes, all these steps are essential ^[i.e. attachment, entry, viral gene expression, virus genome replication, assembly of new virions and exit] there are typically a few optional extras required. These include:
- entry via endosomes
- expression of genes prior to uncoating
- use of nucleus especially DNA viruses
- envelopment using internal membranes e.g. SARS-CoV-2, a RNA positive
note: the unique features of a virus present druggable opportunities
What are the consequences of different virus lifestyles?
- RNA genome - cells do not have a polymerase to make RNA from RNA (i.e. central dogma^[see [Genetics Lecture 1]]). Therefore viruses must encode for it. For negative sense viruses, this needs to be in virion. This makes a very good drug target, since we don’t possess this enzyme
- Location of replication - DNA viruses will enter the nucleus of cells and use their cell machinery, whereas DNA viruses in the cytoplasm will need their own enzymes
- Virion structure– if enveloped, the cell will bud out. If not, it will lyse the cell or parasitise secretion mechanisms. Note that this also impact entry mechanisms
n.b. there is a fine balance between how much damage a virus can do to cells without obliterating cells that they require to propagate*
Describe the spectrum of outcomes of the virus in the host
The spectrum of outcomes of viral infection in a host is dependent on a number of factors, including:
Duration: acute, persistent,, latent or recurrent
Spread: systemic, multi-organ or no spread
Cause of pathology: viral, viral and immune (i.e. a mismatched response), heavy handed response
Outcome: fatal, moderate or asymptomatic
Note this spectrum is not only found between viruses, but in infections of the same virus
What are the cellular outcomes of virus infection?
Going back to the question of viral replication, it is clear that this process is rarely ever simple. All viruses must be able to evade detection in cells. All cells have innate defences, and can tell if something e.g. dsRNA, DNA in cytoplasm, the presence of viral proteins are out of place. An example of cell intrinsic immune defence are antiviral cytokines such as IFN, which sends a ‘warning message’ to neighbouring cells. From there, cells can die quietly (and with cell death, there is no place for virus) or can die spectacularly, resulting in cytokine release and inflammation.
Provide a general overview of viral infection
general overview of viral infection will include
1. Entry into host
2. Primary spread
3. Replication, sometimes followed by secondary and tertiary spread
4. Virus shedding
5. Development of symptoms: a consequence of both the virus and host response
6. Development of an adaptive immune response, T cells then antibodies
7. Fate of host: virus elimination, virus persistence i.e. a stalemate, death of host
- Entry: can enter through breached skin, mucosal membrane, cavities such as the mouth, nose, urogenital or anal canals. Other means of entry include and injection or scratch
- The skin is an excellent barrier, when intact
Tropism
- Tropism can be simply defined as where the virus likes to hang out
- Alternatively, the favoured sites of spread or replication
- Tropism can be considered at three levels:
- cellular i.e. which cells can the virus can go in. This is determined at the simplest level by receptors
- primary tissue or organ: where does virus go immediately upon infection. This is most influenced by the route of transmission, and is usually the upper respiratory tract or otherwise accessible sites for the virus
- secondary tissue or organ: where does virus spread during infection? This is dependent on mechanism of spread as well as the ability to infect. An example of this is the herpes virus, which can infect skin as well as neural tissue; another example of this is the systemic infection as seen with smallpox.
- Not all viruses will spread to a secondary tissue or organ
~All levels are crucial determinants of pathogenesis~
Describe the textbook view of acute infection
This textbook view of infection, where the virus load steadily increases, triggering innate defences, and subsequently the adaptive immune system, correlating with incubation, shedding and symptom presentation **does not really apply to all viruses. Similarly, this does not apply to all people either.
Examples include a severe COVID infection, long COVID, or other long-term chromic infections
List some factors affecting outcome in individuals
- Dose: i.e. more virus means faster tiem to infection*
- Host genetics e.g. receptor polymorphisms and HIV*
- Host age e.g. EBV and mono, RSV, rotaviruses typically in the young ^[not always clear as to why]
- Immune status
- good immunity protects from virus pathology e.g. CMV in transplant patients, but may predispose to immunopathology e.g. pandemic influenza, and over-immune response in the young
- prior exposure may confer partial immunity e.g. dengue, can also lead to bad outcomes
- Route of exposure- can affect pathology as well as chance of spread e.g. smallpox
Describe how we study micro-organisms
Studying replication in culture
Viruses are typically cultured in vitro in either suspension or forming cell layers in flasks. CPE refers to a phenomenon where virus changes shape and appearance of susceptible cells in culture. CPE is predictable, and differs from other types of cell damage. Viruses can also change cell behaviour: infected cells can pass on these changes to their neighbours via secretion.
note: many viruses cannot be grown in culture e.g. noroviruses
additionally some viruses can be grown but are very fastidious
If a virus cannot be grown, there are other options, such as
- studying clinical samples/looking at the virus’ epidemiology
- studying the genes* and proteins of the virus
- using human volunteers(very rare, obviously)
- studying related, culturable viruses
Animal models and pathogenesis
Good animal models allow dissection of pathogenesis, and needs to be backed by human studies
It is important to understand limits of all models; all have intrinsic limits
Examples of models include:
- human viruses in another animal e.g. HSV in mice, flu in mice or ferrets n.b. transmission*
- related animal virus in natural host: SIV vs. HIV, murine vs. human CMV
- humanised or transgenic mice e.g. transplanted with human skin for HPV, Tg mice with CD46 and measles, SCID -Hu mice for HIV
Pathogenesis and spread in people
When studying infected people,, you cannot control when people are infected, host genetics, infection history etc. Therefore you must rely on what the person tells you.
Epidemiology therefore constitutes a crucial public health tool. Often the response to emergent infectious diseases needs to be rapid. Epidemiology should inform all control and vaccine strategies. When epidemiology is linked with molecular genetics, we can learn about virus evolution.
note: public health measures are often maligned as an over-reaction
Why don’t common antibiotics work against viruses?
- Bacterial ribosome is common target and viruses do not encode genes for ribosomes
- Bacterial cell wall is a common target and viruses cannot create structures like the ER and golgi. If they have envelopes, these come from the cell
