The Purloined Virus

Edgar Allen Poe is often credited with the origin of the modern detective story. His first such was The Murders in the Rue Morgue. The idea of murders in a place where dead bodies might be expected gives some insight into his thinking, though he did not capitalize on that at once. (He must certainly have been aware that the Paris morgue was something of a public attraction where the general public could examine unidentified bodies, even if there was no street with the name he used.) He used the idea that we ignore what is ubiquitous explicitly in his third detective story The Purloined Letter. The letter in question was hidden in plain sight by making it resemble an entirely different, and ordinary, letter stored openly.

I will now consider one possible similar problem, a retrovirus which has been ignored because it is ubiquitous. As in earlier posts in this series I will assume the replication and transmission of this virus is adapted to human life cycles, as described before. For most people, most of the time, it would be held latent. This is only a thought experiment, but I found the idea so compelling that I felt a need to insert material about research in areas where we know very little (blank spots on the map) to balance a perceived bias in research literature.

For comparison I'm going to explore changes in research on another delta retrovirus. This has more of the flavor of "looking for your keys under the lamppost", but that is unavoidable if I want to reference widely accepted research. The first confirmed human retrovirus, HTLV-1, was a delta retrovirus, and related research therefore has the longest history. As I have said, I think historical and geographical contingency played a large role in that discovery. We might easily have missed it. With the count of this group of human retroviruses now standing at four, most resulting from separate jumps to a new host, I don't think there is any question such transmission is possible, and even likely on ordinary human time scales.

What do we know about a delta retrovirus in a common domesticated animal? I quote from the Wikipedia article on bovine leukemia virus, used simply because it is up to date and easy to access:

High prevalence of virus was found from testing by USDA. "As part of the 2007 dairy study, bulk tank milk was collected from 534 operations with 30 or more dairy cows and tested with an Enzyme Linked-Immunosorbent Assay (ELISA) for the presence of antibodies against BLV. Results showed that 83.9 percent of U.S. dairy operations were positive for BLV (table 1)."
Is there any reason to assume this percentage is lower in non-dairy cattle? I think I can make a pretty strong case that huge numbers of humans are currently exposed to this virus, directly from cattle, meat and milk, and there were likely many more opportunities for similar viruses to be transmitted to humans prior to the introduction of pasteurization. We now know most infected animals are largely asymptomatic, so inspection alone would not prevent spread.

The next question which arises is the host range of this virus. Here's the pertinent quote:

Natural infection of animals other than cattle and buffalo are rare, although many animals are susceptible to artificial infection. After artificial infection of sheep most animals succumb to leukemia. Rabbits get a fatal AIDS like disease similar to rabbit-snuffles, different from the benign human snuffles. But it is not known whether this naturally occurring rabbit disease is linked to BLV infection. "Although several species can be infected by inoculation of the virus, natural infection occurs only in cattle (Bos taurus and Bos indicus), water buffaloes, and capybaras. Sheep are very susceptible to experimental inoculation and develop tumours more often and at a younger age than cattle. A persistent antibody response can also be detected after experimental infection in deer, rabbits, rats, guinea-pigs, cats, dogs, sheep, rhesus monkeys, chimpanzees, antelopes, pigs, goats and buffaloes.

Now, consider the normal behavior of this virus in a host to which it is well-adapted.

In general BLV causes only a benign mononucleosis-like disease in cattle. Only some animals later develop a B-cell leukemia called enzootic bovine leukosis.

Do any people out there suffer from a "benign mononucleosis-like disease"? Are there clusters of leukemias near them? Are B-cells involved?

Early tests for antibodies to this virus in humans said we were free of these. More recent tests show that such antibodies are widespread.

"Only very recently have currently available and highly sensitive assays such as Western blot and ELISA been employed in testing human sera. Buehring et al (2003) detected antibodies against BLV p24 capsid antigen in 74% of human sera tested using Western blot, while none of the samples that had given the most intense reaction was positive when tested with one of the earlier techniques."
Antibodies could result from consumption of food with viral fragments which are not replication competent in any host. They could also result from slow infections which are below limits of detection. Antibody tests are currently used to screen donated blood for HTLV. If blood with antibodies to BLV were rejected blood banks would have an immediate supply shortage.

Limits to detection are a problem in all efforts at surveillance. This includes those studies looking for the virus in wildlife. It is entirely possible for a marginal infection in an intermediate host to provide an evolutionary stepping stone to yet another host species. This allows an evolving pathogen to undergo some changes in a new host which would not take place in the original host. Domestication of animals has introduced many new opportunities for this process in that last few thousand years. The modified pathogen may evade tests designed to find the original pathogen in the original host species.

There is one other way that humans depart from "natural" processes. It is virtually unknown for mammals to suckle young of other species in the wild. Since this infection is typically transmitted via milk, (and probably via infected cells in that milk rather than free virions,) feeding unpasteurized milk to infants with immature immune systems offers a novel method of transmission. This is one way around the normal limitations of experimental infection. I have only been able to find one paper on infection of chimpanzee's by this route, and it is not encouraging about what might happen with human infants.

I'm not going to sound an alarm about a possible human retrovirus derived from BLV in the future. What I want people to think about is the possibility this took place in the past, before modern medicine was around to notice. In addition to feeding infants unpasteurized cow's milk, people have even consumed raw cow's blood. My introduction to the practice referred to an African tribe safely removed from my environment. Only later did I understand that our European ancestors were mostly peasants who were very short of protein in their diets, and far too poor to slaughter cattle often. (The nobility were under no such constraints, nor were they subject to laws forbidding them to poach game on land they owned, or to fish.) The result was a craving for many things at which we now turn up our noses, including blood pudding. Whatever official assurances were given about transmission of pathogens during the "mad cow" disease scare would not have been true a few centuries ago. We should assume our ancestors were infected with many things. Vertical transmission of a retrovirus via breastfeeding, as with HTLV-1, would then carry the infection forward in time. There are plenty of people alive today who regularly consumed unpasteurized milk as children.

If there were such an endemic infection in humans, as there is in cattle, would we see much different in public health data than we have actually seen?

Comments

Very interesting :)

Side point:
Some of our ancestors drank weak beer and wine very often as their main intake of water, because at least with towns, the water supply wasn't safe.
"Small beer" and watered down wine, or even vinegar, was used to help provide potable water
They didn't understand pathogens, but trial and error had shown alcohol (and vinegar) kept disease at bay.
This also shows the extent of such problems.
 
Not to forget we have been injecting and gulping down biological products that are grown on animal cells lines for the past ... lets say 70 years? What precautionary measures against retroviral contaminants were manufacturers taking 70, 60, 50, even 20 years ago? Even today, there are only 'best practice guidelines' in place, not legal requirements.
 
My primary point is that infections need not be new, or highly lethal in the short term, to cause immense human suffering. I don't know that such undiscovered pathogens are out there, but this is a safer bet than assuming there are none, even if you are merely betting your own money and not lives. The story of BLV also raises the question of when you should believe eminent scientists. Studies showing humans did not have antibodies to BLV go back to 1975. Definitive demonstration that many people do exhibit these antibodies had to wait until 2003.
http://www.ncbi.nlm.nih.gov/pubmed/183678
http://www.ncbi.nlm.nih.gov/pubmed/14709247
 
Lot of people don't want to admit/think of the fact that we are animals, with an ancient past, or that our science is a very very recent endeavour and really knows little. Muh easier/comfortable ot believe we are omniscient gods! :p

Pasteur was ridiculed for his idea of "invisible germs"
took near 100 years after that to actual discover what viruses were
Prions weren't discovered until recently
etc etc.
20 years form now we could discover a type of pathogen we had never imagined, or that retroviruses from our ape ancesor's DNA can lead to sicknesses in ways we'd never imagined.

"Life is like a box of chocolates!"
Yeah some bugger nearly always pinches the nice, soft centers, first! ;)
 
anciendaze, are you suggesting we've all been exposed to lots of little nasties that aren't native to humans, with unknown consequences, possibly serious, since birth? No wonder vaccine makers are exempt from liability.

Makes me think of the Socerer's Apprentice...
 
That is precisely what I'm suggesting, though this post was only part of the argument. This is only one known retrovirus in a single domesticated animal, albeit a common and important one. (You might check on bovine visna virus or bovine immune virus.)
 
This comment came in a private message, but this pertinent section seems sufficiently general to post without getting into questions of identity:


One of the things mentioned in the papers you cited on BLV is that while most other species are resistant to BLV infection through natural infection routes, they are highly susceptible to it, and to serious disease, via direct inoculation, whereas for bovines the situation is reversed. What that brings to mind is the often neglected issue of what 'natural infection routes' actually are. Among other things, for various pathogens, they usually involve interaction with the host mucosal immune system, the first immunological barrier a pathogen faces before it can get to tissue or blood. The results with BLV suggest that BLV has evolved to hijack cells in the mucosal layer and thus easily infiltrate this barrier in its typical host species but not in others. However, the host species and the pathogen have evolved together at the blood and tissue level such that they've reached a sort of equilibrium - the virus isn't too lethal or destructive, and thus is ensured a stable host population. If it is directly inoculated into unfamiliar hosts - i.e. those for which the virus has not evolved the means to easily infect - the virus encounters little evolved immune resistance at the blood and tissue level and the result is a far higher incidence of serious, often lethal disease.
 

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