Herpes viruses got a friend: Helminth parasites can promote the reactivation of latent viral infections

In a fascinating story about co-infections and co-evolution, helminth parasites play a role in a two-signal reactivation pathway of latent infections of herpes-like viruses. 

The helminth Heligmosomoides polygyrus can re-activate latent herpes viruses through the modulation of transcriptior factors and inhibition of anti-viral cytokines. Photograph by Constance Finney.

The helminth Heligmosomoides polygyrus can re-activate latent herpes viruses through the modulation of transcriptor factors and inhibition of anti-viral cytokines. Photograph by Constance Finney.

We all know at least one person who has exhibited the signs of an infection by herpes viruses, as well as their complaints about how this inconvenient infection might re-occur after long dormant periods. In fact, more than 90% of the human population is accounted to latently carry viruses of the herpes family. Although most research on disease mechanisms and host immunity have focused on one-host-one-parasite systems, most vertebrates are known to carry a vast community of parasites, that can behave much like herpes viruses do, alternating between latent and active phases. There is evidence that parasites can interact when in co-infection, however little is known about the precise mechanisms through which these organisms deal with each other when exploring a common host.

In a study published this month in the Science magazine, researchers investigate how helminth parasites influence the end of the latency stages of herpes viruses in murine rodents. The researchers experimentally infect rodents with a herpes-like virus modified to express luciferase – a bioluminescent enzyme that can be used to track the viral replication inside the host. Then, they challenged the same rodents with infections of two different types of helminths, Heligmosomoides polygyrus and Schistosomiasis mansoni, and found out that both parasites promote viral reactivation. Interestingly, the helminths elicit viral ‘awakening’ through a cascade of cell-mediate immunity that starts with the activation of lymphocytes Th2. Once activated by helmintic infections, Th2 cells produce IL-4, which is the crucial factor on the re-activation of herpes viruses. The exit from the latency state is dependent on the expression of one viral gene (gene50), and such expression relies on the bond of a single signaling molecule to gene50. The misfortune of the host and the beauty of co-evolution come from the fact that IL-4, which synthesis is a product of the helminth presence, is the the activator of this one signaling molecule that promotes the expression of the gene necessary for the ‘awakening’ of the herpes virus. Also, IL-4 not only promotes viral gene expression, but also blocks the activity of anti-viral cytokines. Hence, the viruses only exit the latent state when the host immune system provides an ideal medium for their proliferation, by both stimulating viral re-activation and inhibiting anti-viral immunity – all thanks to helminths parasites. What a fine example of co-evolution and organismal adaptation! 

How helminths go viral: Helminth infection activates TH2 cells to release IL-4 and IL-13, both of which ligate the IL-4 receptor (IL-4R) on M2 macrophages. In M2 macrophages harboring latent herpesvirus, the IL-4R activates host cell STAT6, which then acts directly on the key viral gene that initiates viral replication. Figure and caption adapted from Maizels and Gause 2014.

How helminths go viral: Helminth infection activates TH2 cells to release IL-4 and IL-13, both of which ligate the IL-4 receptor (IL-4R) on M2 macrophages. In M2 macrophages harboring latent herpesvirus, the IL-4R activates host cell STAT6, which then acts directly on the key viral gene that initiates viral replication. Figure and caption adapted from Maizels and Gause 2014.

Reese et al, 2014. Helminth infection reactivates latent γ-herpesvirus via cytokine competition at a viral promoter. Science Vol. 345 no. 6196 pp. 573-577.

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7 comments

  1. Hi, I have been trying to find contact information, because I don’t see any I’ll try it this way. Because I was trying to ask for copyright for the picture in this post with the caption: The helminth Heligmosomoides polygyrus can re-activate latent herpes viruses through the modulation of transcriptor factors and inhibition of anti-viral cytokines. Photograph by Constance Finney.

    I like to hear from you soon.

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  2. Long time ago this new was told and nobody like it, Dr. Hulda Clark told everybody that Herpes infect people by the help of parasite. And nobody believe. When I said that I got cured and my PCR RNA test came negative all bulling me and kick me out of forum groups because I clean my body from parasite using Albendazole 400 mg and Sodium Chlorite 28% is been 20 month and the virus never show up or the pain in my hips and back never repeat after use Albenda. Also my General Doctor scream to me because I request de PCR RNA test saying that I will be positive for life. Unfortunatelly for him the test came Negative for both virus. And all the friend that I told to do the same I did have the same result if they dont mantaine relation with a person that have the parasite.

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  3. GJP where can one buy these products and what is the ratio that are to be used and how and for how long does a person have to take them . If you have this information I would be so great full to you . As I am sure you could understand the frustration that comes with this disease Thank you .

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