A Blog by Ed Yong

The Great Herd of Migrating Viruses

Every May, a herd of viruses thunders through East Africa in one of the greatest migrations in the natural world.

For a few months, 1.3 million wildebeest head north through the Serengeti in search of food and water. There are so many of them that their lines can stretch from one horizon to the next. And almost every one of these animals is infected by a virus called acelaphine herpesvirus 1 (AlHV-1).

Wildebeest calves pick up the virus from their mothers within their first few months of life, and carry the infection until they die. The virus causes no symptoms, and doesn’t harm the wildebeest. But domestic cows aren’t so fortunate. If they contract the infection, they develop a disease called malignant catarrhal fever (MCF)—a cancer-like illness where white blood cells start dividing out of control. Once a cow shows symptoms, it’s almost always dead within a couple of weeks.

MCF is a huge threat to the cattle-farming Maasai people of east Africa—the annual wildebeest migration spells death for their livestock. It’s also a problem for any zoos that keep wildebeest, which might infect other hoofed residents. It doesn’t help that there is no treatment. The only way of controlling the disease is to corral animals to prevent them from straying near infected wildebeest.

But Benjamin Dewals from the University of Liege is working on a different solution. By studying how AlHV-1 infects its hosts, he has developed a neutered version that can’t cause MCF and might be able to immunise animals against the wild viruses. It’s a preliminary step towards a vaccine.

The AlHV-1 virus doesn’t cause MCF straight away; it persists in its host for a long time before they start to show symptoms. Dewals found that when calves start coming down with MCF, the virus is unusually passive. It only switches on around 10 percent of its genome, compared to the 45 percent that gets used when it’s actually copying itself and infecting new cells. While many viruses cause disease by infecting and killing new cells, it seems that AlHV-1 does not.

Instead, it persists within the white blood cells of its hosts as free-floating rings of genetic material called episomes. Dewals found that it’s the long-term presence of these rings that causes the cells of the immune system to divide uncontrollably, and triggers MCF. Several other herpes viruses, such as Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpes virus (KSHV) can cause cancer in humans in a similar way. They don’t kill the cells they infect, but encourage them to divide.

This persistent state, known as “latency”, depends on a viral protein called ORF73. When the host cell divides, ORF73 tethers the virus’ genetic material (which normally floats freely) to the DNA of the host. This ensures that the virus ends up in both daughters.

When Dewals deleted the ORF73 protein from synthetic versions of the virus, it could infect cells easily enough but it couldn’t become latent. It could invade, but it couldn’t stay. It couldn’t nudge white blood cells into wanton growth, and it didn’t trigger MCF. Get rid of one protein, and suddenly the virus can’t cause disease.

Best of all, when Dewals exposed rabbits to this neutered virus, they mounted a strong immune response and were later protected against the fully competent version of AlHV-1. Of five rabbits infected with the normal virus, four were dead within a month. But all of those infected by the synthetic virus survived.

It’s not quite a vaccine yet – the team will have to test their neutered virus on a larger number of animals, and on actual cows rather than rabbits. But it’s certainly a first step towards safeguarding domestic animals that are caught in the path of AlHV-1’s annual migration through east Africa.

Reference: Palmeira, Soerl, Van Campe, Boudry, Roels, Myster, Reschner, Coulie, Kerkhofs, Vanderplasschen & Dewals. 2013. An essential role for γ-herpesvirus latency-associated nuclear antigen homolog in an acute lymphoproliferative disease of cattle. PNAS http://dx.doi.org/10.1073/pnas.1216531110

3 thoughts on “The Great Herd of Migrating Viruses

  1. Not sure the environmental impact of such a vaccine has been considered yet… Currently MCV acts as a nice seasonal deterrant to would-be grazers of the Serengeti plains…

  2. Once the Serengeti becomes safe for their cattle how long will take for the booming Maasai population to encroach into the protected areas? The virus is the best protection for one of Earth’s greatest wildlife havens. This is a misguided research that fails to consider the full impacts of its success..

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