Viruses

• Summary
• Introduction to Viruses
• Life Cycles of Viruses
• Behavior of Viruses
  • Behavior by Life Cycle Phase
  • Behavior by Infected Location
• Virus Entities
• Tropism of Viruses
  • Tropism of Virus Entities
• Habitats
  • Life form Habitats
  • Conquering new Habitats
  • Infecting New Species
• Virus Classification

major (re)work in progress, April 2021]

Summary

Viruses are defined as life forms which can’t produce all enzymes required for their metabolism. Topics such as life cycle, capabilities, different behaviors and places of living are introduced.

Introduction to Viruses

Virus

A virus is a life form, that can’t produce all necessary enzymes for its metabolism on its own.

• That it encodes and has enzymes produced distinguishes viruses from viroids.
• That a virus cannot produces all the required enzymes distinguishes them from more self contained forms of life such as eukaryotes and prokaryotes.
• The definition of a virus is by that specific behavior alone (not able to produce all enzymes for its metabolism). Apart from this specific property viruses are very divers. From a molecular viewpoint as diverse as life itself.

Viruses integrate enzymes produced by other forms of life into their metabolism. Since all life forms which are enzymatically independent life forms on today’s earth are cell based [to check] and the metabolisms is inside the cells, viruses need to be within cells to replicate.

Infected Cell

A cell is called infected by a virus if it contains genetic material of the virus which influences the cell’s metabolism.

Infected Object

An object is infected if it contains infected cells. An object can be a tissue, an organ, a structure (e.g. upper respiratory tract) or an organism.

=> An organism is infected if it has some cells that are infected.

These can mean that the virus is replicating inside the cell. A cell is also called infected if only some viral genes are translated and the resulting enzymes are active and thus influence the cells metabolism. To specify, cells in which replication takes place are called host cells.

Infectable Cell

A infectable cell is a cell which can be infected. There are constraints on a cell to be infectable.

Infectable Object

An object is infectable if can become infected. Necessary conditions are (1) infectable cells and this cell must also be reachable. An object can be a tissue, an organ, a structure (e.g. upper respiratory tract) or an organism.

Infectable Organism

An infectable organism is an infectable object where the object is an organism.

There are constraints on a object to be infectable. A necessary condition for an object to become infected is the availability of infectable cells. However this condition is not sufficient, reachability, priming factors and immune evasion are other conditions needed.

Host Cell

A host cell is a cell in which a virus replicates.

A host cell is always an infected cell since to produce new viruses the virus needs to run its metabolism.

Once a virus infects cells, it changes the metabolism of the cell.

Most cells don’t live forever. In multicellular organisms most cells live fare shorter than the organism itself. Some cell lines such as neurons are long-lived, however these long lived cells mostly have their life time limited by the life time of the organism itself. A notable exception are the germ line cells, which have the chance of being part of the cell line giving raise to descendants organisms. Virus infected cells usually die even faster than normal cells. Thus viruses need to jump to next cells. To switch between cells, most viruses, including coronaviruses, have a two phase life cycle.

Life Cycles of Viruses

Different viruses have different life cycles:

• 1 Phase Life Cycle: Some viruses live always within cells and accordingly are only transmitted vertically and not horizontally [to confirm and cite].
• 2 Phase Life Cycle: Most viruses including coronaviruses, have a two phase life cycle. Coronaviruses have a two phase life cycle:
  1. Virion phase: They are born/produced as virion. Virions are similar to seeds of plants in the sense they have no metabolism: passive travel, wait to be activated in the right environment (mostly attached to a cell in the right environment). Once activated virions try to enter the cell.
  2. Metabolic phase: Once inside a cell, a virus uses the cells metabolism to produce proteins and other substances using the structures, ribosomes, enzymes and resources (fatty acids, amino acids and ribonucleic acids) from the host cell. As for all forms of life the ultimate goal is to produce progeny = new virions.
• 4 Phase life cycle: Retroviruses have a four 4 phase cycle [to confirm and cite]:
  1. Sleeping Phase A: Virion Phase (corresponds the virion phase of 2-phase viruses).
  2. Metabolic Phase A: In the metabolic phase A the virion build their genome into the host cells genome.
  3. Sleeping Phase B: The virus genome is part of the host cell DNA.
  4. Metabolic Phase B: The virus genome is transcribed to RNA from the host cells genome. The virus RNA is translated to new virions (corresponds the metabolic phase of 2-phase viruses).

Virion

A virion is the ‘birth-form’ of a virus. The genome and proteins required to infect a cell are usually packed into some form of protective shell. A virion has no active metabolism.

Viruses while outside of cells are present as virions. Virions are passively moved around. Most virions decay but some get matched to an infectable cell. If matched with an infectable cell under the right circumstances, a virion tries to enter the cell.

Virions are similar to seeds of plants: They are dormant and wait for activation. Virions don’t have a metabolism running. They evolved to induce infection on the right circumstances. Once activated/primed cell fusion is initiated by using spring loaded energy stored in the structure of special proteins. The virions phase and the analogies to plant seeds are further discussed in the coronavirus chapter.

Behavior of Viruses

clarifications needed and in work, October 2021

Behavior is used here to denote the situation dependent metabolism including the expression of proteins.

Taxis is possibly a (more) suitable name (than behavior) for the situation specific behavior at the ‘micro’/’small-scale’ level of life-forms. It generalizes the existing use of taxis as stimulus induced movement of cellular life-forms. So the term behavior could be used only when feedback loops via neural networks are involved. (as of October 21, it is in consideration which is the more concise usage)

The behavior of viruses can be viewed

• by life cycle phase
• by the infected locations in a host

Behavior by Life Cycle Phase

Behavior Virion Phase

in rework, June 2021

To infect a cell the virions need to be activated. The activation factors determine the behavior of virions:

• Environmental factors throughout the lifetime of a virion and around the cells mainly determine entry:
  • physical environment: e.g. temperature
  • chemical environment: e.g. pH value
  • biological environment: e.g. Virions are primed for cell entry by specific proteins The spike proteins of coronaviruses need one or more priming steps. which usually means cleaved by proteases for cell entry. This cleaving can require proteases and the right physiological conditions [citations in work]
• Cell Type
  • Matching Receptor on the target cell membrane
  • biochemistry inside the cells

The behavior in the virions phase in mostly determined by the proteins and lipids accessible from the outside. In the case of coronaviruses the spike plays a central role in the virion phase behavior.

Behavior Metabolic Phase

[in early work]

The metabolic phase is varies widely across viruses. The metabolic phase of coronaviruses is described on the coronavirus page in the section metabolic phase.

Investigating the Behavior

The behavior in the virion phase is better known than the behavior in the metabolic phase.

• The cell entry can be investigated with reprogrammed viruses (often retroviruses) expressing the coronavirus spikes and transfected cells (mostly standard laboratory cell-lines where some genes are changed so they express the desired receptors). Neither the transfected cell need to behave similar to the cells which are naturally infected nor the reprogrammed viruses behave similar once inside the cell.
• To investigate the metabolic phase, ideally one could look into the cells. Often one observes the cells just from the outside e.g. observing cell damage.
• Detecting virus ‘metabolites’/virion building blocks such as RNA or produced proteins is suitable to get hints for the intracellular behavior.

Behavior by Infected Location

Cell Specific Behavior

Cell specific behavior is used on this page to describe how a virus behaves upon match of a virion to a specific cell type i.e. the behavior in specific cells.

• Virion Phase: Questions relevant for the behavior of viruses in the virion state:
  • To which receptors under which conditions the virions attach?
  • Factors inducing activation and cell entry of virions?
• Metabolic Phase: Questions relevant for the behavior of viruses in the metabolic state:
  • Do the cells support viral replication?
  • Is cell death induced upon infections?
  • Are the viruses neutralized once inside the cell?

The cell behavior is the combination of the virion behavior which determines whether a cell infection takes place and the behavior in the metabolic phase which determines the changes in the cells metabolism induced upon infection.

• The cell environment shouldn’t deactivate the virus or alarming the immune system.
• The cell should be able to produce many virions and thus should have a capable metabolism.

Tissue Specific Behavior

The tissue tropism depends on:

• Infectable cells in the tissue
• Movement within the tissue i.e. reaching the next cell in the tissue
  • Coronaviruses usually infect the apical cell layer of the respiratory tract epithelium initially. Most virions are released again on the apical side to spread via the covering fluids. Some virions are released on the basal layer and can yield further infections deeper in the tissue or spread via the blood stream, especially if released from the intestine from where they can leave and infect the next host.
  • Coronaviruses are to big to diffuse efficiently inside most tissues.
• Immune defenses present in the tissue.

Virus Entities

[in work and explorative]

Organisms which are usually considered as a whole and not as single cells. Similarly for viruses infecting organisms, often to grasp the full picture it is necessary to consider all viruses as an entity and not as unrelated. Viruses can show different behaviors in different cells and upon different situations:

• Communication: As cells in multicellular organisms communicate, viruses communicate too e.g. by producing virus like particles, which are similar to virions but don’t contain the whole machinery to replicate and thus just influence other cells or other viruses.
• Differentiation: DNA/Retro viruses can in theory encode the same differentiation mechanisms as eukaryotic cells. In fact the cellular differentiation is often driven by endogenous retroviruses. RNA viruses don’t encode the same mechanisms as DNA based forms of life e.g. for gene expression. However they still are able to show different behaviors in different situations.

Virus Entity

A Virus Entity or Virus Organism denotes all infected cells in an organism resulting from a single infection occurrence. Upon a new infection the infections can interact and give rise to a new entity.

A multicellular organism can arise from only one cell, similarly usually only few viruses of a virus entity transmit to a new host and give rise to a new virus entity.

Virus entities/organisms are a concept I haven’t seen about in literature. Similar concepts may exists possibly under different names.

Tropism of Viruses

Explorative section. The term tropism is used here to denote the growth of virus entities which is slightly different and more general than used in literature.

In literature, tropism is mostly used when viruses replicate well in some cells or tissues (general notes on tropism in the chapter life form chapter). On this page, viral tropism is used as follows:

Virus Tropism

A virus has a tropism for an object or a location if it is frequently infects an object. The tropism for a cell is called Cell Tropism and for tissues/organs Tissue Tropism.

Cell Tropism

A virus has a tropism for a certain cell type if these cell are readily infected.

Usually viruses within an organisms can’t be considered as independent which gives rise to the concept of virus entities.

Tropism of Virus Entities

Tropism describes how virus entities growth, where the virus entity consists of the infected cells in an organism i.e. when the population of viruses is viewed as a virus entity tropism denotes the growth preferences of a virus entity.

Tissue Tropism

Tissue tropism denotes tissues which are frequently by a virus [entity].

So tropism denotes how virus entities growth within an organisms. Going on level up to determine which organisms are infected under which circumstances is discussed in Habitats.

Habitats

Explorative section. The term virus habitat is to my knowledge not common in literature.

The behavior of viruses describes how viruses behave under different circumstances, the tropism of viruses how a virus entities growths within a host, habitats denotes the locations where viruses live. Environments satisfying the behavior and tropism constraints and additionally are frequently reached by virus entities, form a place of living or habitat.

Habitat

The Habitat of a virus are the locations which are frequently infected. The locations can be cells, tissues, organs, life forms or groups of life forms.

E.g. Sars-CoV-2 frequently infects alveolar epithelial cells =>

• the alveolar epithelial cells are a cell habitat
• the alveolar epithelium a tissue habitat
• the lower lungs - where these tissue is - are an organ habitat for SARS-2
• humans are an organism habitat (called hosts) for SARS-2.

Core Habitat

The core habitat are habitat locations which are relevant for the survival of a virus lineage.

Side Habitat

The side habitat denotes infected locations which are not relevant for the spread i.e. viruses lines in a side will not survive.

Life form Habitats

Life forms which serve as habitats are called hosts.

Host

A host of a virus is life form which is part of the life cycle of a virus lineage.

Organisms in the habitat of a virus are frequently infected.

Endemic Hosts

A virus strain is endemic in a collection of organisms if that collection is a habitat of the virus.

Sometimes it is helpful to name frequently infected organism which play no role for the survival of virus lineages:

Side Host

A Side Host or Terminal Host of a virus is a host but the infections yield no relevant spread of the virus. E.g. the virus cannot efficiently replicate or leave the host. These infections can be viewed as side-effects of the random virus spread. Viruses can evolve such that a Side Host becomes a Host.

Conquering new Habitats

The virus can get attached to a cell types or hosts the given strain which are not part of its current habitat. Most likely the entity of viruses doesn’t manage to adapt to the new target. However if a lineage of viruses manages to adapt to the new target, this becomes a new habitat. The new habitat can be:

• a new cell type
• a new tissue type
• a new organism type: infecting new species

Since in new habitats there often is a different evolutionary drive, the line of viruses can give rise to a new virus strain.

Infecting New Species

With no metabolism running virions can not move on their own and so they can’t steer their movement to only reach their hosts. If a virus strain reaches organism of some species, there are several cases:

• the organism reached is a host -> continue life cycle
• the organism reached is not a host:
  • it is not infectable -> break
  • it is infectable. This yields an interspecies infection. Again two cases:
    • the virus entity can not efficiently leave to keep up the chain of infections: on average less than one virion (i.e. reproduction factor is < 1)-> break i.e. the infection chain is a cul-de-sac and the organisms are side hosts or terminal hosts
    • on average more than one virion of a virus entity can leave and infect another organism (i.e. the reproduction factor is > 1) -> gives rise to a new life cycle: an interspecies jump has happened. Since the evolutionary drive changes, this can give raise to a new virus strain.

Interspecies Infection

An interspecies infection is when an animal which is not an existing host animal becomes infected by a virus strain.

Interspecies Jump

An interspecies jump denotes a transmission to a new species and the species becomes a new host i.e. the new species becomes part of the habitat of the virus. The virus strain may evolve to an adapted new strain.

Zoonosis

A zoonosis is an interspecies jump where the new host species is human (homo sapiens).

So an interspecies infection denotes a transmission without spread in the new species. If these infections occur frequently the new species becomes a side host but not a natural host. Frequent infections allow the virus strain to adapt to the new host. The host may become part of a life cycle of a possibly new virus strain which is then an [interspecies jump]

Virus Classification

By definition, a virus is a life form encoding proteins but not all. This definition is very broad so often further classifications/grouping are done.

The goal of classification is usually to group things together which are similar to some properties or behavior of interest.

Features of interest for viruses are:

• Viruses can be classified by the hosts they infect. E.g. bacteriophages infect bacteria.
• Genetic and metabolic similarity. Viruses exists across all the different storage forms used by life forms.
• Structural Similarity. E.g. viruses can be classified into enveloped and non-enveloped viruses.