false assumptions about viral infections

[anciendaze]

For as long as I have been reading viral research, which is coming up on a decade, there have been some pretty vicious academic fights over the criteria necessary to establish a disease as a viral infection. In the very obscure field of multipart viruses in plants there has recently been an earthquake in understanding.

Some viruses with multiple parts, each having a defect and infecting a different cell, can still work together to constitute an infectious disease. Here's the original paper.

There are also multipart viruses in animals, but the same behavior has not been established largely because nobody even considered this possible.

I can't help but think of this in connection with HERVs and research showing that viral sequences dismissed as junk DNA are active in a number of infectious diseases. In considering how infections in different cells would interact, at least in animals, I can't help but think of communication between cells via episomes, another poorly studied subject.

If you check infectious disease literature for possible examples of multipart infections you will find mention of rickettsial diseases, but up to now there has been little discussion of possible multipart viruses.

 

[Pyrrhus]

Very interesting, thanks for sharing.

There are also multipart viruses in animals, but the same behavior has not been established largely because nobody even considered this possible.

There is a related phenomenon, researched by Raul Andino, of ”viral quasi-species”. In this scenario you have many defective versions of a virus in a single cell. Although each individual defective virus is missing a part needed for infectious pathology, other defective viruses in the same cell supply the missing parts, and as a whole, the collective “quasi-species” is capable of infectious pathology.

 

[sea]

Welcome @anciendaze nice to see you here

 

[anciendaze]

I'm still processing the very idea of multipart viruses, and discovering other subjects about which I know very little. (Yesterday was lost to income tax preparation, which is now behind me. I avoided paying taxes by the simple expedient of losing money.)

Quasispecies work to explain defective viruses infecting a single cell, as Pyrrhus says. If they can infect different cells, and still work together, something more is required. I want people to notice the evolutionary reasoning that led to the decision to investigate a virus with eight parts.

These viruses have always been baffling, even to virologists who knew about them. Everyone assumed that they could only reproduce if all the segments infected the same host cell. But the risk of losing a piece, and so dooming the others, skyrockets as the number of pieces goes up. In 2012, two researchers calculated that the odds of successfully getting every segment in the same cell become too low with anything more than three or four segments. FBNSV, with its eight segments, “should never have evolved,” Blanc says. Its mere existence suggests “that something must be wrong in the conceptual framework of virology.”

If different parts of a virus with different defects infect different cells there must be intercellular communication particularly suited to communication between viruses. Above I've mentioned episomes, and some infections do produce more of these. This is however a very uncertain means of communication, and the probability of supplying a missing feature needed by the infection has a major effect on the probability of a successful infection requiring multiple parts.

A second method of communication, targeting specific cells, could take place via mobile immune cells forming immune synapses. This has already been studied in connection with NK cells, and we have heard arguments over the role of NK cells in ME/CFS. I was impressed by the role of ion-channels in formation of immune synapses with NK cells, as I've already encountered patients called CFS patients who had ion-channel disorders.

At this point I realized I have absolutely no idea how plants mount immune defenses. My first thoughts are that mobile immune cells are only characteristic of animals. If I'm right this would be a major difference to consider when looking for corresponding infections in humans. There needs to be some evolutionary payoff for breaking an infection into multiple parts, which carries obvious costs, and evading immune defenses seems a likely explanation. What I know at present about T-cells recognizing intracellular infections depends on those cells presenting multiple epitopes which identify the infection. If some epitopes are on different cells, while proteins are supplied to perform needed functions, it would seem this would be a very clever way to evade immune defenses.

 

[Pyrrhus]

Quasispecies work to explain defective viruses infecting a single cell, as Pyrrhus says. If they can infect different cells, and still work together, something more is required.

This is not exactly what you’re talking about, but it is possible for a viral quasispecies to move from one cell to another. In the case of enteroviruses, this phenomenon has recently been named “stealth spheres”. A “stealth sphere” is a single membraned extra-cellular vesicle enclosing multiple defective copies of the enterovirus. This vesicle, which may be released at the synaptic terminals of neurons, effectively transmits the virus from one cell to another, without forming any complete viral particles at all.

I suppose if the receiving cell already has a few defective viruses, the “stealth sphere” could provide any missing pieces needed to kickstart viral pathology. It is interesting to note that these “stealth spheres” often contain ribosomes as well, which is important because not all neuronal dendrites contain the ribosomes necessary to transcribe the viral proteins that lead to viral pathology.

I want people to notice the evolutionary reasoning that led to the decision to investigate a virus with eight parts.

Again, this is not exactly what you’re talking about, but it is interesting to note that the influenza virus has 8 genetic segments and it still manages to package all 8 segments, and only those segments, into a single viral particle. (The segmented nature of the influenza genome is one of the reasons that new influenza strains can so easily arise. If two different flu strains infect the same cell, they can swap segments, creating an entirely new strain.)

 

[anciendaze]

Another feature of influenza virus is that it is an RNA virus, as are many enteroviruses. These are less stable than DNA viruses. In addition to passing proteins or viral particles between cells we need to consider naked RNA sequences. These are often assumed to be too fragile to have much influence, but could be transmitted via episomes or immune synapses with mobile immune cells.

One surprise about HIV was that dendritic cells could transmit the virus without themselves being infected. They keep antigens passed to them in a separate compartment. This suggests a means of viral interaction not previously considered, if an infection can use pieces of RNA or proteins to interact without needing actual virions.

 

[Alvin]

Merged thread

I haven't read it yet but in case its interesting

It is a truth universally acknowledged among virologists that a single virus, carrying a full set of genes, must be in want of a cell. A virus is just a collection of genes packaged into a capsule. It infiltrates and hijacks a living cell to make extra copies of itself. Those daughter viruses then bust out of their ailing host, and each finds a new cell to infect. Rinse, and repeat. This is how all viruses, from Ebola to influenza, are meant to work.

But Stéphane Blanc and his colleagues at the University of Montpellier have shown that one virus breaks all the rules.

https://www.theatlantic.com/science...nary-discovery-of-a-distributed-virus/584884/