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What's a poor virus to do? part 2

Blog entry posted by anciendaze, Sep 18, 2011.

Just in case anyone is confused by this perspective, I want to emphasize that a virus is unlikely to have mental processes of any kind. We don't normally even call things living if they can be crystallized and stored like salt. My approach is a literary device to help us view the problem from a new angle.

That said, what happens to a virus, adapted as described, when it reaches the laboratory? First, the overwhelmingly likely case is that it will reach the lab in the form of latent provirus in cells, not virions. Second, variability which makes it hard for cellular defenses and immune systems to deal with will also frustrate many attempts at detection based on specific sequences. Third, culturing will face a problem: the latent provirus doesn't need to do anything to survive as long as the cell it infects. Even if virions are present, if they are adapted to replicate slowly over decades it will be difficult to culture them in days.

From the viral point of view nothing much is required of it. It is waiting on signals which will either activate its genes, or cause the cell it inhabits to replicate the virus in the process of replicating its own DNA. The signals which control viral replication include hormones associated with sexual maturity and stress. The culture has no endocrine system to generate these. The virus is also lying low to evade immune response, but the culture has no immune system either -- not that the virus can tell.

My point is that a virus well adapted to living humans as described earlier will not do much of anything. It is waiting on conditions indicating another infection or sexual maturity. Unless it is in an immune system cell, and this cell is deliberately activated, causing it to divide, nothing is likely to result.

Even if a few virions are present, and infect cells in culture, they are not going to replicate quickly. Their evolution in human hosts has caused them to slow replication to a level those hosts can tolerate for many years, and wait for signals to produce virions in an appropriate context. Without deliberate actions by researchers these will never arrive.

What strains of virus will replicate quickly? Defective ones. The simplest way to produce such a virus is to delete part of the wild-type genome. Culturing is like a race. The strains most likely to win this race in a reasonable time will all be defective versions of the well-adapted human pathogen. They must be competent to replicate, but need do nothing else. Many clever adaptations to natural hosts can be discarded.

I'm proposing that the event which created the virus contaminating the 22Rv1 cell line was not a recombination, but a deletion. Other strains without that deletion are known. These are likely to be closer to the wild type virus in humans.

A process of piecing together fragments to identify the wild type took place to find existing reference strains. We may not have reached the end of the trail. We still don't know many things we need to know about the wild-type virus. There very well might be deletions in all reference strains. Sequencing a number of independent isolates could give us the information we need to fill in the gaps. This could have been done a year ago.

In fact, there is an existing source of possible sequences to fill gaps. Endogenous retroviral sequences are all over human genomes. The prevailing wisdom is that these are millions of years old and harmless to hosts. This is true for some, not all. Simply because one member of a family of viruses was endemic in ancestors millions of years ago we should not reject the idea that a member of that family currently infects a species. There are numerous counterexamples in other species.

The HHV-6 mentioned earlier, though not a retrovirus, does sometimes integrate into chromosomes, (by processes not well understood.) When it does, the locations are not completely random, and not identical in most humans. When we find the same sequence at the same location in mother and child it is a safe bet it was inherited. Active HHV-6 infection occurs in nearly all humans at some time in their life. We are seeing an exogenous sequence in the process of becoming endogenous.

The main reason an endogenous sequence like HERV-W is said to be inactive is that we have not observed it actively infecting humans. Or have we? Sequence information shows it would be grouped with gamma retroviruses. Proteins expressed by the ERVWE1 gene have been observed in people with MS or schizophrenia. Viral RNA has been found in cerebrospinal fluid of individuals with recent onset of schizophrenia. Envelope proteins have been found in MS patients. There are two obvious possibilities here: 1) HERV-W is being activated and causing disease; 2) an exogenous virus closely related to HERV-W is still infecting people. Either way, ignoring a virus because it resembles a HERV is foolish. Molecular mimicry is an excellent way to evade host cell defenses. An aspiring retrovirus could scarcely ask for a better example than those presented by successful ancestors. A virus integrated into the germ line of many individuals has achieved tenure.

I am well aware most researchers in virology prefer to work on pathogens which do a better job of meeting their expectations. After a century or more in which intelligent and energetic people have applied Koch's postulates to many pathogens it becomes more and more likely the ones remaining undetected will be different. In the case of chronic disease, I believe this has happened in far more than one diagnostic category.
anciendaze

About the Author

As the name suggests, I am old and dazed. The avatar illustrates my rule of thumb: "Hang on! This ride isn't over."
  1. anciendaze
    ..Enid, anciendaze- if you haven't read it already, evolutionary biologist Paul Ewald's "Plague Time" is worth reading. He thinks most chronic illnesses are caused by viruses, and explains the reasons he thinks many have evolved to cause chronic, vs. acute, illness. I have not read it, but will put it on my list. At this point, I don't think I can attribute my ideas to any single source. This is not to claim originality, I simply haven't seen the combination of features which have evolved slowly in my thinking over the last couple of years in another form. This may be due to my own oversight, but I would hesitate to burden any author I have read with claims of agreement with what I have written. My mistakes are my own.
  2. searcher
    This is a great post and I agree that researchers' inability to identify the pathogens causing chronic diseases is due to Koch's postulates not being applicable (or potentially difficult to test in cases of long lag times between initial infection and symptoms.) Enid, anciendaze- if you haven't read it already, evolutionary biologist Paul Ewald's "Plague Time" is worth reading. He thinks most chronic illnesses are caused by viruses, and explains the reasons he thinks many have evolved to cause chronic, vs. acute, illness.
  3. Enid
    What's left of it ! - and when my computer doesn't have the same problem - but the so to speak mechanics of viral behaviours (unravelling of) is very interesting.
  4. anciendaze
    Very interesting anciendaze - from what I can follow as a non scientist. As a general observation it seems so many "diseases" are now being found to have viral origins. As a well known Biologist said "this will be the century of the virus". Looking very like it in the discoveries in this field now.I'll have more to say later. Though the research will be more difficult than in the past, there are new tools available, and the pay off will be enormous. What I'm suggesting here could apply to many manifestations of chronic infection.
    Bit less of the "poor old virus" please - seems we are necessarily locked into a warfare with the "clever" blighters. ! Got your attention didn't it?
  5. Enid
    Very interesting anciendaze - from what I can follow as a non scientist. As a general observation it seems so many "diseases" are now being found to have viral origins. As a well known Biologist said "this will be the century of the virus". Looking very like it in the discoveries in this field now.

    Bit less of the "poor old virus" please - seems we are necessarily locked into a warfare with the "clever" blighters. !