A team of scientists from The Scripps Research Institute and other institutions has solved the structure of a key protein from the virus that caused last year's "swine flu" influenza¹ epidemic². The structure reveals that the virus shares many features with influenza viruses common in the early 20th century, helping³ to explain why, in general, older individuals have been less severely⁴ affected⁵ by the recent outbreak than younger ones. The team's findings were published in the March 25, 2010, issue of Science Express, an advance, online publication of selected research papers from the prestigious⁶（有声望的） journal Science.

In the study, the team describes the structure of the hemagglutinin（血细胞凝集素） (the influenza virus envelope protein包膜蛋白) from the H1N1 swine flu virus that triggered the pandemic in 2009 and is still circulating in the human population. The team then compared the swine flu hemagglutinin protein with a range of different human H1N1 flu viruses in the past century.

"Parts of the 2009 virus are remarkably⁷ similar to human H1N1 viruses circulating in the early 20th century," said Scripps Research Professor Ian Wilson, who was the senior author of the study. "Our findings provide strong evidence that exposure to earlier viruses has helped to provide some people with immunity⁸（免疫力，豁免权） to the recent influenza pandemic."

The information should be useful for scientists and public health officials as they respond to current and future pandemics（全国流行的，普遍的） .

Flu Outbreaks

Influenza is a common viral infection of the lungs that affects millions of people annually⁹ and is a leading cause of death in the United States, contributing to around 50,000 deaths per year. Serious influenza outbreaks such as the deadly "Spanish flu" of 1918 have occurred when a virus adapted to（适应于，适合） birds jumps directly into humans or reassorts and infects another species, such as the pig, and then jumps into humans. Similar outbreaks occurred in 1957 and 1968.

"For a pandemic to occur, there needs to be a naïve population, whose immune systems have not learned to recognize the virus and who can be infected," explained Rui Xu, a research associate in the Scripps Research Wilson lab who was first author of the paper with graduate student Damian Ekiert, also of the Wilson lab. "A pandemic outbreak is different from the seasonal¹⁰ flu, in which existing flu viruses circulate in the human population, gradually mutating as time goes on."

The most recent influenza outbreak, dubbed¹¹（被称为） the "swine flu" by the media due to its recent origin in pigs, was first reported in Mexico in April 2009. The virus has now spread worldwide, and has contributed to（促成，有助于） at least 16,000 deaths, according to the World Health Organization. A vaccine¹² is now available, but the virus remains¹³ a public health concern.

Almost as soon as the outbreak was first reported last April, the Scripps Research team set out to better understand the new influenza virus by examining its structure.

Collaborating¹⁴ with colleagues at Mount Sinai School of Medicine, who provided a clone of the major surface antigen（表面抗原） from the emerging virus, A/California/04/2009 (CA04), , the scientists called on a technique called x-ray crystallography（结晶学） . In this method, scientists produce quantities of the viral protein and try to crystallize it. This crystal is then placed in front of a beam of x-rays, which diffract（分散，衍射） when they strike the atoms in the crystal. Based on the pattern of diffraction, scientists can reconstruct the shape of the original molecule¹⁵.

The scientists chose to focus on the structure of the virus's hemagglutinin, a protein that is abundantly（丰富地，大量地） displayed on the viral surface. In addition to enabling the virus to infect cells of the host organism, hemagglutinin is the main antigenic determinant（抗原定子，抗原决定蔟） on the virus—in other words, it is what the immune system primarily recognizes and responds to by making antibodies (a type of immune molecule) and mounting an immune defense¹⁶. Vulnerability to an individual influenza infection depends on how well a person's immune system recognizes the hemagglutinin.

The scientists' initial experiments went extraordinarily¹⁷ well, and by June, the team was able to reconstruct the structure of the swine flu hemagglutinin.