We write so much here about influenza A virus that you might get the idea it is an especially clever virus, always changing genetically in ways that allow it to perform new and nastier tricks. But other viruses are capable of doing the same thing, and one of them West Nile Virus (WNV), is currently becoming a a more persistent and serious public health hazard, all because of a clever little genetic trick it learned in the last decade or so.
WNV has been around longer than that, although we didn’t have a problem with it in North America until 1999, when this mosquito-borne disease showed up, in of all places, the Borough of Queens in New York City. Like influenza, WNV is primarily a disease of birds, infecting humans relatively rarely and then only as dead-emd hosts. And, like influenza, its genetic material is a single strand of
positive sense RNA. WNV is classified as a flavivirus and belongs to a complex of viruses with similar immunologic reactivity (called the Japanese Encephalitis serocomplex) which includes other diseases of birds and mammals (including humans) spread by mosquitoes, namely Japanese Encephalitis and St. Louis Encephalitis virus. WNV infections in humans ranges from asymptomatic or slight flu-like illnesses with fever to a full blown potentially lethal encephalitis (brain inflammation) with paralysis. It was first found in 1937 in the blood of a woman in the West Nile district of Uganda, and has been responsible for relatively localized outbreaks (some quite large) in Asia, Eastern Europe, the Middle East and Africa. Female mosquitoes, seeking a blood meal prior to ovulation, suck the blood of an infected bird, amplify the virus in their bodies and then transfer it to another bird or a mammal such as a horse or a human, where it causes infection. Humans don’t produce enough virus in their blood to allow msquitoes to pick it up from them and transfer it to another person, as happens with yellow fever, so humans are a dead end for the virus and not really part of its cycle in nature, which is primarily bird to bird. We are incidental hosts.
Which brings us to the clever genetic change WNV underwent sometime in the 1990s. WNV is capable of infecting a tremendous range of birds. So far over 300 species have been shown to be infected, although most of the WNV dead bird reports are in crows and jays. This may be because they are more susceptible or because they are large birds whose corpses are much more conspicuous. Whatever the reason, the lethality of WNV in crows increased suddenly after a specific genetic change which is only now being discovered and seems specific to North America — for now:
Since its 1999 introduction into the U.S., the virus has cut crow populations almost in half in some regions, researchers said in May. [Aaron Brault’s study, from the University of California, Davis, School of Veterinary Medicine], published in the journal Nature Genetics, suggests the culprit is a small mutation in a gene that makes a protein, called helicase, that unwinds RNA, or ribonucleic acid, a molecule that carries genetic messages.
The mutation was first seen in Israel in 1997, Brault said. Before that, most West Nile outbreaks caused fairly mild disease in people, and the virus grew so slowly in birds that it was difficult to recover from their bodies.
Today, crows infected by the North American strain of West Nile harbor so much virus that a single mosquito can take on a million copies in a single blood meal. Researchers are trying to determine how the mutation permits the virus to grow faster in crows, Brault said. (John Lauerman, Bloomberg)
Genetic success for a virus is to make as many copies of itself as it can. The mutation in the helicase gene allows it to make many more copies of itself in birds and this allows mosquitoes to transfer it more successfully to another bird or an unlucky human. This is the counterpart to a mutation in a bird flu virus that would make a more efficient bird to human or human to human transmission.
This season looks like it might be particularly nasty one for WNV in North America. So far there are 308 cases reported to CDC, compared to 192 at this point last year. A third of the cases have severe neurological involvement, with 11 deaths compared to 6 deaths at a comparable point in 2006.
So while we worry about preparing for an influenza pandemic, we should remember there are other pathogens out there that can do us in. Mosquito-borne disease once ravaged the United States, with yellow fever causing devastating epidemics in northern cities like Philadelphia. Malaria was endemic throughout the Mississippi Valley 19th century. If we are to make our communities more resilient to the shock of emerging and re-emerging infectious disease, we need to be careful not to take our eye off the main strategy: to harden and strengthen our public health and social service infrastructures so they can handle many different problems. A strategy that focuses on antivirals and vaccines for influenza will do little for WNV or whatever else there is out there. A robust public health system will helop us with all comers.
Not that you’ve heard me say this before, of course.