My enemy’s enemy is my… enemy?

Like a kind of Russian doll infection, a prolific human parasite—responsible for almost 250 million infections annually—can itself harbour a parasite, a virus. You might reasonably feel a sense of something akin to schadenfreude; glad it’s getting a dose of its own medicine, so to speak…

But you may be too hasty.

The very presence of this virus—though it doesn’t infect human cells—in its parasite host could be making infections worse, or even stymying our attempts at  relieving the infection.

The parasite in question, with around 3.7 million people infected in the US alone, is the most common protozoan infection in the industrialised world: Trichomonas vaginalis (TrV). It infects the human genitourinary tract of both men and women causing Trichomoniasis; in fact, it can only live in the human genitourinary tract (an ‘obligate human parasite’). Women are more likely to experience symptoms than men, and while generally mild,  it can be bad. Its worst effects are seen in reproduction where it can cause infertility, miscarriage, pre-term delivery and low birth weight.

Among the other effects of TrV is an increase in susceptibility to other sexually transmitted diseases like HIV and the cancer causing HPV. Therefore, with such high prevalence in the population, being able to effectively treat it is vital. Fortunately, there is a treatment: the antibiotic Metronidazole. However, like with bacteria, TrV is developing resistance; forcing dosages, and therefore the risk of side effects, higher.

The virus that infects TrV is called Trichomonavirus. It is a dsRNA* virus and at least half of all clinical samples of TrV are infected it. Normally, you might expect that to be a good thing, considering how viruses can make other animals ill, maybe it would do the same to a protozoan? And, with some viruses, you may be right.

In the excellent ‘A Planet of Viruses’, Carl Zimmer tells the story of the Canadian-born physician Felix d’Herelle, who, in the pre-antibiotic world of 1917, discovered that viruses that infect bacteria (‘bacteriophages’) can be isolated and used to effectively treat bacterial diseases in people (though this isn’t an approach which seems to have caught on…): The enemy of my enemy can be my friend.

To be honest, I really couldn't find something else to put here to break up the text... well, not something that wasn't copyrighted or, well, distasteful...

Artists impression of a generic virus…

Sadly though, Trichomonasvirus is neither silent to us, nor benign, as researchers from the Harvard Medical School have recently discovered, the enemy of my enemy can be my enemy too.

To understand how this could happen, a little explanation of how the immune system works is helpful.

Picture your body as a well-guarded castle; it has two basic types of defence, representing the two arms of the immune system: the innate and the adaptive. The first is an indiscriminate defence; the high walls and barriers, traps and alarms triggered when something is in the wrong place.  The second type of defence is adaptive, the guards patrolling, who can learn and recognise an intruder, or repeat offender, and deal with them by name.

Trichomonasvirus falls foul of the first line of defence. There are some things your body just knows shouldn’t be there, something  immediately recognised as a danger signal that triggers an alarm. dsRNA, Trichomonasvirus’ genetic material, is one such thing. The alarm is a receptor, TLR-3, that recognises dsRNA, sure sign of a virus—it’s such a sure sign of a virus that TLR-3 remains pretty much unchanged between even fruit flies and humans. Once triggered, TLR-3 starts a cascade of reactions and signals that start up, or maintain, the process of inflammation.

It seems the human host can detect not just the TrV infection, but also the presence of the virus in its parasite host, and this can make infections even worse. This may also explain another observation of TrV infection.

Normally when we treat an infection successfully we expect the symptoms to fade shortly after, but with TrV, even if treated and there is no longer TrV present, it doesn’t improve reproductive outcomes; the inflammation—though to be mostly responsible for them— doesn’t go away. It can even increase the chance of preterm delivery. So what’s going on?

The researchers from Harvard Medical School have an idea. They think that:

It is conceivable that virus released by dying protozoa during conventional antibiotic treatment fuels pathogenic inflammatory responses linked to preterm birth and facilitating risk of HIV and other STIs.

In other words, the antibiotic pops the bubble of TV, releasing a flood of virus particles, like glitter from a burst balloon, that the body detects and interprets as an attack, unleashing an immune response—inflammation.

Viruses that infect protozoans, or possibly even bacteria, could turn out to be a bigger problem than we ever realised. There have been similar findings in mice infected with a different protozoan, called Leishmania, which also harbours its own dsRNA virus. Again the presence of the virus seems to worsen symptoms of the infection.

However, as the Harvard team point out, now we know virus harbouring parasites play a more complicated role in disease than we did before—now we’ve revealed yet another layer of nature’s complexity—we can start work on understanding and developing new strategies for treating these kinds of ‘Russian doll’ infections.

Reference: Fichorova, R.N. et al., 2012. Endobiont Viruses Sensed by the Human Host – Beyond Conventional Antiparasitic Therapy N. Fasel, ed. PLoS ONE, 7(11), p.e48418. Available at: http://dx.plos.org/10.1371/journal.pone.0048418 [Accessed November 8, 2012].

*Viruses tend to be grouped by how they store their genetic material, be in single stranded (ss) or double stranded (ds) DNA, or its sister molecule RNA. Trichomonavirus is a dsRNA virus. Humans only have dsDNA, so anything else is generally treated by the body as highly suspicious.

 

Image Credits:

Top: Antonio Pereira-Neves and Marlene Benchimol, Santa Ursula University, Rio de Janeiro, Brazil

An electron micrograph depicting the Trichomonas vaginalis parasite adhering to vaginal epithelial cells collected from vaginal swabs. A non-adhered parasite (right) is pear-shaped, whereas the attached parasite is flat and amoeboid.

Body: Generic Virus,  Oliver Burston. Wellcome Images, images@wellcome.ac.uk, An artists interpretation of a generic virus particle. Copyrighted work available under Creative Commons by-nc-nd 2.0 UK, see http://images.wellcome.ac.uk/indexplus/page/Prices.html