Dynasty: Influenza virus in 1918 and today

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Source: http://www.eurekalert.org/pub_releas...-div062609.php

Public release date: 29-Jun-2009


Contact: Anne A. Oplinger
aoplinger@niaid.nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases
Dynasty: Influenza virus in 1918 and today



The influenza virus that wreaked worldwide havoc in 1918-1919 founded a viral dynasty that persists to this day, according to scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. In an article published online on June 29 by the New England Journal of Medicine, authors Anthony S. Fauci, M.D., Jeffery K. Taubenberger, M.D., Ph.D., and David M. Morens, M.D., argue that we have lived in an influenza pandemic era since 1918, and they describe how the novel 2009 H1N1 virus now circling the globe is yet another manifestation of this enduring viral family.

"The 1918-1919 influenza pandemic was a defining event in the history of public health," says NIAID Director Dr. Fauci. "The legacy of that pandemic lives on in many ways, including the fact that the descendents of the 1918 virus have continued to circulate for nine decades."

Influenza viruses have eight genes, two of which code for virus surface proteins?hemagglutinin (H) and neuraminidase (N)?that allow the virus to enter a host cell and spread from cell to cell. There are 16 H subtypes and 9 N subtypes, and, therefore, 144 possible HN combinations. However, only three (H1N1, H2N2 and H3N2) have ever been found in influenza viruses that are fully adapted to infect humans. Other combinations, such as avian influenza H5N1, occasionally infect people, but they are bird viruses, not human viruses.

"The eight influenza genes can be thought of as players on a team: Certain combinations of players may arise through chance and endow the virus with new abilities, such as the ability to infect a new type of host," says Dr. Morens, Senior Advisor to the NIAID Director. That is likely what happened to spark the 1918 pandemic, he adds. Scientists have shown that the founding virus was an avian-like virus. The virus had a novel set of eight genes and?through still-unknown mechanisms?gained the ability to infect people and spread readily from person to person.

Not only did the 1918 H1N1 virus set off an explosive pandemic in which tens of millions died, during the pandemic the virus was transmitted from humans to pigs, where?as it does in people?it continues to evolve to this day. "Ever since 1918, this tenacious virus has drawn on a bag of evolutionary tricks to survive in one form or another?and to spawn a host of novel progeny viruses with novel gene constellations, through the periodic importation or exportation of viral genes," write the NIAID authors.

"All human-adapted influenza A viruses of today?both seasonal variations and those that caused more dramatic pandemics?are descendents, direct or indirect, of that founding virus," notes Dr. Taubenberger, Senior Investigator in NIAID's Laboratory of Infectious Diseases. "Thus we can be said to be living in a pandemic era that began in 1918."

How exactly do new influenza gene teams make the leap from aquatic birds to a new host, such as people or other mammals? What factors determine whether infection in a new host yields a dead-end infection or sustained, human-to-human transmission, as happened in 1918? Research on such topics is intense, but at this time definitive answers remain elusive, notes Dr. Morens.

It is known that the human immune system mounts a defense against the influenza virus's H and N proteins, primarily in the form of antibodies. But as population-wide immunity to any new variant of flu arises, the virus reacts by changing in large and small ways that make it more difficult for antibodies to recognize it. For nearly a century, then, the immune system has been engaged in a complicated pas de deux with the 1918 influenza virus and its progeny, say the NIAID authors. The partners in this dance are linked in an endless effort to take the lead from the other.

While the dynasty founded by the virus of 1918 shows little evidence of being overthrown, the NIAID authors note that there may be some cause for optimism. When viewed through a long lens of many decades, it does appear that successive pandemics and outbreaks caused by later generations of the 1918 influenza dynasty are decreasing in severity, notes Dr. Morens. This is due in part to advances in medicine and public health measures, he says, but this trend also may reflect viral evolutionary pathways that favor increases in the virus's ability to spread from host to host, combined with decreases in its tendency to kill those hosts.

"Although we must be prepared to deal with the possibility of a new and clinically severe influenza pandemic caused by an entirely new virus, we must also understand in greater depth, and continue to explore, the determinants and dynamics of the pandemic era in which we live," conclude the authors.

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(See a diagram of the genetic relationships among human and swine influenza viruses.)

For more information on influenza visit PandemicFlu.gov for one-stop access to U.S. Government information on avian and pandemic flu. Also, see NIAID's flu portal and the CDC's Seasonal Flu page.

NIAID conducts and supports research?at NIH, throughout the United States, and worldwide?to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

The National Institutes of Health (NIH)?The Nation's Medical Research Agency?includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

Reference: DM Morens et al. The persistent legacy of the 1918 influenza virus. New England Journal of Medicine. DOI: 10.1056/NEJMp0904819 (2009).

[Shiloh]

Re: Dynasty: Influenza virus in 1918 and today

Source: http://www.cidrap.umn.edu/cidrap/con...istory-jw.html


Experts look for clues in 1918 pandemic virus family tree

Lisa Schnirring * Staff Writer

Jun 29, 2009 (CIDRAP News) ? To outside observers, the novel H1N1 virus spreading quickly to every corner of the globe must seem like it came out of nowhere, but the organism is a fourth generation of the 1918 pandemic virus and comes from an H1N1 family tree that is colorful and complex, according to two historical reviews that appear today in the New England Journal of Medicine (NEJM).

Understanding the history of swine influenza viruses, particularly their contribution to the 1918 pandemic virus, underscores the need to better comprehend zoonotic viruses as well as the dynamics of human pandemic viruses that can arise from them, the authors report in an early online NEJM edition.

The world is still in a "pandemic era" that began in 1918, wrote three experts from the National Institute of Allergy and Infectious Diseases (NIAID), senior investigator David Morens, MD, medical epidemiologist Jeffery Taubenberger, MD, PhD, and NIAID director Anthony Fauci, MD.

The 1918 virus has used a "bag of evolutionary tricks" to survive in humans and pigs and to launch other novel viruses, they wrote. "The 2009 H1N1 pandemic virus represents yet another genetic product in the still-growing family tree of this remarkable 1918 virus."

The novel H1N1 virus' complex evolutionary history involved genetic mixing within human viruses and between avian- and swine-adapted viruses, gene segment evolution in multiple species, and evolution from the selection pressure of herd immunity in populations at different times, the group wrote, adding. "The fact that this novel H1N1 influenza A virus has become a pandemic virus expands the previous definition of the term,"

Though any new virus is unpredictable, Fauci and his colleagues wrote that in this pandemic era, severity appears to be decreasing over time, with an evolutionary pattern that appears to favor transmissibility over pathogenicity.

Two researchers from the University of Pittsburgh, in a review article on the emergence of H1N1 viruses, wrote that viral adaptation to a new host species is complex, but the 1918 influenza A H1N1 virus was unusual because it emerged from a bird source in pigs and humans at the same time. In contrast, researchers have said the new H1N1 virus probably emerged from swine to humans. The authors are Shanta Zimmer, MD, from the medical school, and Donald Burke, MD, from the graduate school of public health.

Previous research suggests that antibody specificity against the 1918 human influenza virus diverged quickly from swine influenza viruses, and genetic differences in hemagglutinin (HA) continue to show the same type of rapid divergence between human and swine viruses, they wrote.

Researchers still don't know why H1N1 retreated in 1957 for the next 20 years, though likely factors include high levels of existing homologous immunity plus the sudden appearance of heterologous immunity from a new H2N2 strain, Zimmer and Burke wrote.

Cross-species transfers of swine influenza H1N1 cropped up a few times over the next two decades, and human H1N1 didn't surface again until 1977, presumably because of a laboratory accident in the former Soviet Union. This event marked a first in interpandemic history: the cocirculation of two influenza A viruses.

The authors wrote that it's difficult to predict how well the pandemic strain will compete against the seasonal H1N1 virus. Both viruses share three gene segments with their remote 1918 descendant: nucleocapsid, nonstructural, and HA. They pointed out that studies of B-cell memory response in 1918 pandemic survivors showed that the neutralizing body against HA was specific and long-lasting.

Cell-mediated immunity may also affect competition between the two viruses, the authors wrote. Though it's not clear if cytotoxic T lymphocytes clinically protect humans, they have been shown to reduce viral shedding, even in the absence of antibodies against HA and neuraminidase.

"Cytotoxic T lymphocytes that are generated by seasonal influenza viruses against conserved epitopes might provide heterotypic immune responses that could dampen transmission, even in the absence of measurable antibody protection," Zimmer and Burke wrote.

Morens DM, Taubenberger JK, Fauci AS. The persistent legacy of the 1918 influenza virus. N Engl J Med 2009 Jul 16;361(3):225-29 [Full text]

Zimmer SM, Burke DS. Historical perspective?emergence of influenza A (H1N1) viruses. N Engl J Med 2009 Jul 16;361(3):279-85 [Full text]