The killer flu of 1918

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"Scientists suspect killer flu of 1918 brewed for years

By LAURAN NEERGAARD, ASSOCIATED PRESS, February 16, 1999

WASHINGTON - The 1918 flu that killed more than 20 million people may have quietly percolated for several years, maybe even trading back and forth between pigs and people, until suddenly growing strong enough to become the world's worst pandemic.

That's the latest theory from the Armed Forces Institute of Pathology, which reported yesterday that researchers for the first time have completely analyzed a critical gene from the killer influenza virus.

The gene probably "was adapting in humans or in swine for maybe several years before it broke out as a pandemic virus," said molecular biologist Ann Reid, lead author of the study published in the Proceedings of the National Academy of Sciences.

But "we can't tell whether it went from pigs into humans or from humans into pigs," she said. ...

Occasionally a strain tough enough to kill millions emerges, and experts warn that the world is overdue for another pandemic.

That's why understanding the 1918 flu's genes are important. Scientists need to know what made that strain the deadliest ever - and why it struck down mostly young, healthy people - to better react if similar killer flu emerges again.

Most experts believe that genetically stable flu viruses reside harmlessly in birds, but that occasionally one of these bird viruses infects pigs. The swine immune system attacks the virus, forcing it to change genetically to survive. If it then spreads to humans, the result can be devastating.

In two other pandemics - the 1957 Asian flu and 1968 Hong Kong flu - viruses apparently made a fast jump from birds to pigs to humans. That's because human flu genes from those pandemics appear very similar to avian flu genes.

But the new study finds no similarity between those bird genes and a key gene in the 1918 flu.

Reid studied lung tissue preserved from autopsies of two soldiers who died from influenza, at Fort Jackson, S.C., and Camp Upton, N.Y., and from the frozen corpse of an Alaskan woman. Reid fully mapped the hemagglutinin gene, which is key to influenza infection taking hold.

She discovered that the hemagglutinin closely resembles mammal genes.

So instead of making that fast bird-pigs-people jump that scientists expect in a pandemic, the 1918 virus apparently evolved in mammals - either pigs or humans - over many years before suddenly mutating into a mass killer. It may have percolated in humans as early as 1900, she said.

But Reid can't tell if pigs developed the mutation that turned the virus into a killer and gave it to people - or if people gave it to pigs.

Among the evidence: A huge wave of mild influenza struck people during the spring of 1918, but no pigs were sick. Then the flu struck again in the fall. This time it suddenly killed millions of people, and this time pigs were sick, too - but people who had had the mild spring flu were reported to be immune. ..."

Flu is not the only disease which humans seem to acquire from other animals:

NIAID-Supported Scientists Discover Origin of HIV-1

NIAID News Release
National Institute of Allergy and Infectious Diseases
National Institutes of Health
January 31, 1999

Experts have wondered about the origin of HIV ever since the epidemic emerged almost two decades ago. The uncertainty launched a variety of conspiracy theories, some suggesting that AIDS was a government plot, created purposely to kill.

Now, research presented at an AIDS conference Sunday provides what scientists say is convincing proof to the contrary: The virus got its start in the forests of Africa when humans caught it from chimpanzees. In fact, they say the virus has spread at least three times from chimps to people.

``This is absolutely evidence to put (conspiracy theories) to rest,'' Dr. Constance Benson of the University of Colorado said.

Even scientists who scorned those theories have been unsure where AIDS actually arose. Some suspected chimps, while others thought monkeys or other primates could have been the source.

The latest discovery was made by Dr. Beatrice Hahn of the University of Alabama at Birmingham, who tracked HIV's ancestor to a virus that has long infected one of the four subspecies of chimp that live in Africa.

Today scientists reported that they have discovered the origin of HIV-1, the virus responsible for the global AIDS pandemic. A subspecies of chimpanzees native to west equatorial Africa has been identified as the original source of the virus.

Beatrice H. Hahn, M.D., of the University of Alabama at Birmingham, a grantee of the National Institute of Allergy and Infectious Diseases (NIAID), led the international team of investigators. They describe their findings in the February 4, 1999, issue of Nature. The journal moved the normal press embargo ahead to coincide with Dr. Hahn's presentation of the study details on the opening night of the 6th Conference on Retroviruses and Opportunistic Infections in Chicago.

"This is an important finding with significant potential," notes Anthony S. Fauci, M.D., NIAID director. "We now have chimpanzee isolates of simian immunodeficiency virus [SIVcpz] that have been shown by careful molecular analysis to be closely related to HIV-1. Furthermore, this virus infects a primate species that is 98 percent related to humans. This may allow us -- if done carefully and in collaboration with primatologists working to protect this endangered species -- to study infected chimpanzees in the wild to find out why these animals don't get sick, information that may help us better protect humans from developing AIDS."

Until now, HIV-1's origin had been unclear. Although most scientists suspected that the virus descended from a primate species, only three chimpanzees infected with viruses related to HIV-1 had been documented, and one of these viruses correlated only weakly with HIV-1.

When Dr. Hahn and her collaborators recently identified a fourth chimpanzee infected with SIVcpz, they decided to use this opportunity to carefully examine all four viruses and the animals from which they were derived.

While chimps have long been suspected as the source, there have been a lot of loose ends that made people uncomfortable drawing that conclusion, said Dr. Beatrice Hahn.

Whatever its origins, HIV is a recent affliction of people. At last year's Conference on Retroviruses and Opportunistic Infections, Dr. David Ho and others from the Aaron Diamond AIDS Research Center at Rockefeller University presented evidence that the virus probably first infected humans in the 1940s or early 50s.

At the opening of this year's meeting, Hahn made the case that this event almost certainly occurred in west equatorial Africa when someone caught the virus from a chimp, perhaps after killing the animal for food.

Hahn said her team nailed down the connection by analyzing frozen tissue saved from a chimp named Marilyn that died from complications of childbirth at a U.S. Air Force primate center 14 years ago.

This fourth sample turned up when a colleague cleaning out a lab freezer ran across Marilyn's specimens and sent them to Hahn. Her team was able to perform various kinds of genetic analysis that were unavailable when the chimp died.

Then the Alabama team used molecular analysis techniques to study all four examples of the virus.

They found that three of the four were genetically extremely similar to the human AIDS virus. They included one gene, called vpu, that also is part of HIV but not of other AIDS-like viruses that infect monkeys.

With sophisticated genetic techniques, they analyzed the four SIVcpz isolates and compared them with various HIV-1 viruses taken from humans. They also determined the subspecies identity of the chimpanzees: three belonged to a subspecies native to west equatorial Africa, Pan troglodytes troglodytes. The fourth, the chimpanzee infected with a virus most unlike HIV-1, belonged to an east African subspecies known as Pan troglodytes schweinfurthii.

As it turns out, the three isolates from the Pan troglodytes troglodytes chimpanzees strongly resemble the different subgroups of HIV-1, namely groups M (responsible for the pandemic), N and O (both found only in west equatorial Africa). Their investigation also revealed that some of the viruses resulted from genetic recombination in the chimpanzees before they infected humans.

Their other significant find, Dr. Fauci notes, is that the natural habitat of these chimpanzees directly coincides with the pattern of the HIV-1 epidemic in this area of Africa. Putting all these pieces of the puzzle together, Dr. Hahn and her colleagues conclude that Pan troglodytes troglodytes is the natural reservoir of HIV-1 and has been the source of at least three independent occurrences of cross-species virus transmission events from chimpanzees to humans.

The authors believe that HIV-1 was introduced into the human population when hunters became exposed to infected blood. Furthermore, they speculate that humans might still be at risk for cross-species transmission because the bushmeat trade -- the hunting and killing of chimpanzees and other endangered animals for human consumption -- is still common practice in west equatorial Africa.

This new report suggests that preserving the wild chimpanzee populations will be crucial for further carefully designed studies to better understand how cross-species virus transmission occurs and how infected chimpanzees resist disease, studies that in turn may lead to new strategies for designing HIV drugs and vaccines.

References:

F Gao, E Bailes, DL Robertson, Y Chen, CM Rodenburg, SF Michael, LB Cummins, LO Arthur, M Peeters, GM Shaw, PM Sharp and BH Hahn. Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes. Nature 397, 436-41 (1999).

RA Weis and RW Wrangham. From Pan to pandemic. Nature 397, 385-6 (1999).

NIAID is a component of the National Institutes of Health (NIH). NIH is an agency of the U.S. Department of Health and Human Services.

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

HISTORICAL SKETCH OF AVON, OHIO, TO 1974

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