Photo of a computer-generated 3D rendering of a flu virus.

First childhood flu helps explain why virus hits some people harder than others

Photo of a computer-generated 3D rendering of a flu virus.

A computer-generated 3D rendering of a flu virus. Photo Credit: Dan Higgins/Courtesy of CDC/Douglas Jordan

Why are some people better able to fight off the flu than others? Part of the answer, according to a new study, is related to the first flu strain we encounter in childhood.

Scientists from UCLA and the University of Arizona have found that people’s ability to fight off the flu virus is determined not only by the subtypes of flu they have had throughout their lives, but also by the sequence in which they are been infected by the viruses. Their study is published in the open-access journal PLoS Pathogens.

The research offers an explanation for why some people fare much worse than others when infected with the same strain of the flu virus, and the findings could help inform strategies for minimizing the effects of the seasonal flu.

In addition, UCLA scientists, including Professor James Lloyd-Smith, who also was a senior author of the PLoS Pathogens research, recently completed a study that analyzes travel-related screening for the new novel coronavirus 2019-nCoV. (The research is under review; a preprint is online.)

The researchers report that screening travelers is not very effective for the 2019 coronavirus — that it will catch less than half of infected travelers, on average — and that most infected travelers are undetectable, meaning that they have no symptoms yet, and are unaware that they have been exposed. So stopping the spread of the virus is not a matter of just enhancing screening methods at airports and other travel hubs.

“This puts the onus on government officials and public health officials to follow up with travelers after they arrive, to isolate them and trace their contacts if they get sick later,” said Lloyd-Smith, a UCLA professor of ecology and evolutionary biology. Many governments have started to impose quarantines, or even travel bans, as they realize that screening is not sufficient to stop the spread of the coronavirus.

One major concern, Lloyd-Smith said, is that other countries, especially developing nations, lack the infrastructure and resources for those measures, and are therefore vulnerable to importing the disease.

“Much of the public health world is very concerned about the virus being introduced into Africa or India, where large populations exist that do not have access to advanced medical care,” he said.

The researchers, including scientists from the University of Chicago and the London School of Tropical Hygiene and Medicine, have developed a free online app where people can calculate the effectiveness of travel screening based on a range of parameters.

“Our finding concerning the effectiveness of screening for the coronavirus is not a criticism of screening practices being done by public health officials in the United States or elsewhere,” Lloyd-Smith said.

He said that the biology and epidemiology of the virus itself makes infection extremely difficult to detect in its early stages, because the majority of cases show no symptoms for five days or longer after exposure.

“My colleagues and I know there is a lot of speculation online about the coronavirus and how it spreads,” Lloyd-Smith said “People should look to trusted sources for accurate information, such as the Centers for Disease Control and Prevention, the Los Angeles County Department of Public Health, and the peer-reviewed scientific literature.”

Solving a decades-old question

The PLoS Pathogens study may help solve a problem that had for decades vexed scientists and health care professionals: why the same strain of the flu virus affects people with various degrees of severity.

A team that included some of the same UCLA and Arizona scientists reported in 2016 that exposure to influenza viruses during childhood gives people partial protection for the rest of their lives against distantly related influenza viruses. Biologists call the idea that past exposure to the flu virus determines a person’s future response to infections “immunological imprinting.”

The 2016 research helped overturn a commonly held belief that previous exposure to a flu virus conferred little or no immunological protection against strains that can jump from animals into humans, such as those causing the strains known as swine flu or bird flu. Those strains, which have caused hundreds of spillover cases of severe illness and death in humans, are of global concern because they could gain mutations that allow them to readily jump not only from animal populations to humans, but also to spread rapidly from person to person.

In the new study, the researchers investigated whether immunological imprinting could explain people’s response to flu strains already circulating in the human population and to what extent it could account for observed discrepancies in how severely the seasonal flu affects people in different age groups.

To track how different strains of the flu virus affect people at different ages, the team analyzed health records that the Arizona Department of Health Services obtains from hospitals and private physicians.

Two subtypes of influenza virus, H3N2 and H1N1, have been responsible for seasonal outbreaks of the flu over the past several decades. H3N2 causes the majority of severe cases in high-risk elderly people and the majority of deaths from the flu. H1N1 is more likely to affect young and middle-aged adults, and causes fewer deaths.

The health record data revealed a pattern: People first exposed to the less severe strain, H1N1, during childhood were less likely to end up hospitalized if they encountered H1N1 again later in life than people who were first exposed to H3N2. And people first exposed to H3N2 received extra protection against H3N2 later in life.

The researchers also analyzed the evolutionary relationships between the flu strains. H1N1 and H3N2, they learned, belong to two separate branches on the influenza “family tree,” said James Lloyd-Smith, a UCLA professor of ecology and evolutionary biology and one of the study’s senior authors. While infection with one does result in the immune system being better prepared to fight a future infection from the other, protection against future infections is much stronger when one is exposed to strains from the same group one has battled before, he said.

The records also revealed another pattern: People whose first childhood exposure was to H2N2, a close cousin of H1N1, did not have a protective advantage when they later encountered H1N1. That phenomenon was much more difficult to explain, because the two subtypes are in the same group, and the researchers’ earlier work showed that exposure to one can, in some cases, grant considerable protection against the other.

“Our immune system often struggles to recognize and defend against closely related strains of seasonal flu, even though these are essentially the genetic sisters and brothers of strains that circulated just a few years ago,” said lead author Katelyn Gostic, who was a UCLA doctoral student in Lloyd-Smith’s laboratory when the study was conducted and is now a postdoctoral fellow at the University of Chicago. “This is perplexing because our research on bird flu shows that deep in our immune memory, we have some ability to recognize and defend against the distantly related, genetic third cousins of the strains we saw as children.

“We hope that by studying differences in immunity against bird flus — where our immune system shows a natural ability to deploy broadly effective protection — and against seasonal flus — where our immune system seems to have bigger blind spots — we can uncover clues useful to universal influenza vaccine development.”

Around the world, influenza remains a major killer. The past two flu seasons have been more severe than expected, said Michael Worobey, a co-author of the study and head of the University of Arizona’s department of ecology and evolutionary biology. In the 2017–18 season, 80,000 people died in the U.S., more than in the swine flu pandemic of 2009, he said.

People who had their first bout of flu as children in 1955 — when the H1N1 was circulating but the H3N2 virus was not — were much more likely to be hospitalized with an H3N2 infection than an H1N1 infection last year, when both strains were circulating, Worobey said.

“The second subtype you’re exposed to is not able to create an immune response that is as protective and durable as the first,” he said.

The researchers hope that their findings could help predict which age groups might be severely affected during future flu seasons based on the subtype circulating. That information could also help health officials prepare their response, including decisions about who should receive certain vaccines that are only available in limited quantities.

The research was funded by the National Institutes of Health, the National Science Foundation, DARPA and the David and Lucile Packard Foundation. In 2018, the NIH’s National Institute of Allergy and Infectious Diseases announced a strategic plan to develop a universal flu vaccine.

The study’s co-authors are Rebecca Bridge of the Arizona Department of Health Services and Cecile Viboud of the Fogarty International Center at the NIH.

This article originally appeared in the UCLA Newsroom.

Image of Kabuki actor performing

UCLA receives $25 million from Uniqlo founder for Japanese literature and culture studies

Image of Kabuki actor performing

Renowned Kabuki actor Nakamura Kyozo performing the role of a lion in “Shujaku jishi” at the Glorya Kaufman Dance Theater in an event for students co-sponsored by the Yanai Initiative and the Japanese Ministry of Culture (November 14, 2019). (Credit: Ning Wong Studios)

UCLA has received a $25 million gift from Tadashi Yanai, the chair, president and CEO of Japan-based Fast Retailing and founder of clothing company Uniqlo. The funds will endow the Tadashi Yanai Initiative for Globalizing Japanese Humanities, which will bolster UCLA’s status as a leading center for the study of Japanese literature, language and culture.

The gift is the largest from an individual donor in the history of the UCLA College’s humanities division. A previous donation of $2.5 million from Yanai in 2014 created the Yanai Initiative, a collaboration between UCLA and Waseda University, one of Japan’s most prestigious universities. The program supports academic and cultural programming and enables student and faculty exchanges between the two universities. This latest gift will ensure the initiative’s long-term future.

“Mr. Yanai’s extraordinary gifts are a testament to UCLA’s long-standing commitment to educate global citizens who can thrive in careers — and cultures — anywhere in the world,” said UCLA Chancellor Gene Block. “The Tadashi Yanai Initiative for Globalizing Japanese Humanities will have a profound and lasting impact on this campus.”

Photo of Tadashi Yanai

UCLA has received a $25 million gift from Tadashi Yanai, the chair, president and CEO of Japan-based Fast Retailing and founder of clothing company Uniqlo. (Credit: Fast Retailing Co., Ltd.)

The Yanai Initiative is housed in the UCLA College department of Asian languages and cultures and directed by Professor Michael Emmerich. The latest gift will fund and establish an endowed chair in Japanese literature and will fund conferences, public lectures, faculty research, cultural performances and community outreach. It will support graduate and postdoctoral fellowships and undergraduate awards.

“It has been inspiring to see all of the creative, innovative programming — both academic and cultural — that this project has realized over the past five years,” Yanai said. “Now that we are making it permanent, I’m excited to see how it will continue to transform the Japanese humanities in a global context. At the same time, I hope this gift will give others a chance to remember how crucial the humanities are, and, in their own way, to recommit.”

The gift also triggers matching funds from the Humanities Centennial Match and the UCLA Centennial Scholars Match to support UCLA graduate students in Japanese humanities and other areas of study.

“Mr. Yanai’s gift is a visionary investment in a field of increasing interest to humanities scholars, students and people everywhere,” said David Schaberg, UCLA’s dean of humanities. “Thanks to his generosity, UCLA will lead the way in research and teaching in Japanese humanities, bringing new attention to a rich culture that has captured people’s imaginations for centuries.”

Schaberg said another benefit of the gift is that it will deepen UCLA’s partnership with Waseda.

In addition to funding fellowships, symposia, lectures and academic workshops, Yanai’s previous donation supported a range of cultural programs, including a five-day series of events featuring actor Nomura Mansaku, who was designated a “living national treasure” by the Japanese government; a retrospective of films by Palme d’Or recipient Hirokazu Kore-eda; and “The Art of the Benshi,” which introduced Los Angeles audiences to the early 20th century performance art in which narrators bring silent movies to life with live music accompaniment.

“During the past five years, Mr. Yanai’s generosity has enabled us to do so much for students and for the Japanese humanities not just at UCLA, but across the country and around the world,” Emmerich said. “We’ve been able to organize major cultural events across Los Angeles, drawing thousands of participants. I never imagined I would be able to say that all this was only the beginning. I can’t express how grateful we all are to Mr. Yanai for his generosity, his incisive advice and his commitment.”

The gift was facilitated through a designated donations program run by the Japan Foundation, which is dedicated to promoting cultural and intellectual exchange with Japan. Over the past three decades, the foundation has helped advance and fund numerous cultural programs at UCLA.

View this release in Japanese

UCLA Opens World’s 1st Institute To Study Kindness

UCLA receives $20 million to establish UCLA Bedari Kindness Institute

Jennifer and Matthew C. Harris ‘84.

The Bedari Foundation, established by philanthropists Jennifer and Matthew C. Harris, has given $20 million to the UCLA College to establish the UCLA Bedari Kindness Institute.

The institute, which is housed in the division of social sciences, will support world-class research on kindness, create opportunities to translate that research into real-world practices, and serve as a global platform to educate and communicate its findings. Among its principal goals are to empower citizens and inspire leaders to build more humane societies.

“Universities should always be places where we teach students to reach across lines of difference and treat one another with empathy and respect — even when we deeply disagree,” UCLA Chancellor Gene Block said. “The UCLA Bedari Kindness Institute will bring the best thinking to this vital issue and, I think, will allow us to have a real social impact on future generations.”

The institute, which will begin operating immediately, will take an interdisciplinary approach to understanding kindness — through evolutionary, biological, psychological, economic, cultural and sociological perspectives. It will focus on research about the actions, thoughts, feelings and social institutions associated with kindness and will bring together researchers from across numerous disciplines at UCLA and at external organizations.

The inaugural director of the institute is Daniel Fessler, a UCLA anthropology professor whose research interests include exploring how witnessing acts of remarkable kindness can cause an uplifting emotional experience that in turn motivates the observer to be kind. Studies by Fessler and his colleagues have shed light on why some people are open to that type of “contagious kindness” experience.

The Bedari Foundation is a private family foundation whose aim is to enable significant cultural shifts in the fields of health and wellness, community displacement and environmental conservation.

“Our vision is that we will all live in a world where humanity discovers and practices the kindness that exists in all of us,” said Matthew Harris, the foundation’s co-founder and a 1984 UCLA graduate. “Much research is needed to understand why kindness can be so scarce in the modern world. As we seek at Bedari to bridge the divide between science and spirituality, through the establishment of the UCLA Bedari Kindness Institute we hope to educate and empower more and more people in the practice of kindness.”

Already, a range of researchers at UCLA are studying the types of questions that will be the basis of the institute’s work. For example, UCLA anthropologists are examining how kindness spreads from person to person and group to group. UCLA sociologists are analyzing how people who regularly act unkind might be encouraged to engage in kind acts instead, and UCLA psychologists are researching how kindness can improve people’s moods and reduce symptoms of depression. Others are pursuing research on changes in neurobiology and behaviors resulting from mindfulness, and how those changes can influence kindness and people’s mental, physical and social well-being.

“In the midst of current world politics, violence and strife, the UCLA Bedari Kindness Institute seeks to be an antidote,” said Darnell Hunt, dean of the UCLA division of social sciences. “Rooted in serious academic work, the institute will partner and share its research on kindness broadly in accessible formats. The Bedari Foundation’s extraordinary gift is truly visionary and we are grateful for its support and leadership.”

The Kindness Institute will provide seed funding for research projects that examine the social and physical mechanics of kindness and how kindness might be harnessed to create more humane societies. It also will provide mindfulness awareness training to students, faculty and staff and in underserved Los Angeles communities, and host an annual conference at which presenters will examine new discoveries in kindness research, among other activities.

“The mission of the Kindness Institute perfectly aligns with that of the division of social sciences, where engaging the amazing diversity and social challenges shaping Los Angeles routinely inspires research that has the potential to change the world,” Hunt said.

The gift is part of the Centennial Campaign for UCLA, which is scheduled to conclude in December.

Study shows how serotonin and a popular anti-depressant affect the gut’s microbiota

Senior author Elaine Hsiao says researchers hope to build on their current study to learn whether microbial interactions with antidepressants have consequences for health and disease. Photo: Reed Hutchinson/UCLA

A new study in mice led by UCLA biologists strongly suggests that serotonin and drugs that target serotonin, such as anti-depressants, can have a major effect on the gut’s microbiota — the 100 trillion or so bacteria and other microbes that live in the human body’s intestines.

Serotonin — a neurotransmitter, or chemical messenger that sends messages among cells — serves many functions in the human body, including playing a role in emotions and happiness. An estimated 90% of the body’s serotonin is produced in the gut, where it influences gut immunity.

The team — led by senior author Elaine Hsiao and lead author Thomas Fung, a postdoctoral fellow — identified a specific gut bacterium that can detect and transport serotonin into bacterial cells. When mice were given the antidepressant fluoxetine, or Prozac, the biologists found this reduced the transport of serotonin into their cells. This bacterium, about which little is known, is called Turicibacter sanguinis. The study is published this week in the journal Nature Microbiology.

“Our previous work showed that particular gut bacteria help the gut produce serotonin. In this study, we were interested in finding out why they might do so,” said Hsiao, UCLA assistant professor of integrative biology and physiology, and of microbiology, immunology and molecular genetics in the UCLA College; and of digestive diseases in the David Geffen School of Medicine at UCLA.

Hsiao and her research group reported in the journal Cell in 2015 that in mice, a specific mixture of bacteria, consisting mainly of Turicibacter sanguinis and Clostridia, produces molecules that signal to gut cells to increase production of serotonin. When Hsiao’s team raised mice without the bacteria, more than 50% of their gut serotonin was missing. The researchers then added the bacteria mixture of mainly Turicibacter and Clostridia, and their serotonin increased to a normal level.

That study got the team wondering why bacteria signal to our gut cells to make serotonin. Do microbes use serotonin, and if so, for what?

In this new study, the researchers added serotonin to the drinking water of some mice and raised others with a mutation (created by altering a specific serotonin transporter gene) that increased the levels of serotonin in their guts. After studying the microbiota of the mice, the researchers discovered that the bacteria Turicibacter and Clostridia increased significantly when there was more serotonin in the gut.

If these bacteria increase in the presence of serotonin, perhaps they have some cellular machinery to detect serotonin, the researchers speculated. Together with study co-author Lucy Forrest and her team at the National Institutes of Health’s National Institute of Neurological Disorders and Stroke, the researchers found a protein in multiple species of Turicibacter that has some structural similarity to a protein that transports serotonin in mammals. When they grew Turicibacter sanguinis in the lab, they found that the bacterium imports serotonin into the cell.

In another experiment, the researchers added the antidepressant fluoxetine, which normally blocks the mammalian serotonin transporter, to a tube containing Turicibacter sanguinisThey found the bacterium transported significantly less serotonin.

The team found that exposing Turicibacter sanguinis to serotonin or fluoxetine influenced how well the bacterium could thrive in the gastrointestinal tract. In the presence of serotonin, the bacterium grew to high levels in mice, but when exposed to fluoxetine, the bacterium grew to only low levels in mice.

“Previous studies from our lab and others showed that specific bacteria promote serotonin levels in the gut,” Fung said. “Our new study tells us that certain gut bacteria can respond to serotonin and drugs that influence serotonin, like anti-depressants. This is a unique form of communication between bacteria and our own cells through molecules traditionally recognized as neurotransmitters.”

The team’s research on Turicibacter aligns with a growing number of studies reporting that anti-depressants can alter the gut microbiota. “For the future,” Hsiao said, “we want to learn whether microbial interactions with antidepressants have consequences for health and disease.” Hsiao wrote a blog post for the journal about the new research.

Other study co-authors are Helen Vuong, Geoffrey Pronovost, Cristopher Luna, Anastasia Vavilina, Julianne McGinn and Tomiko Rendon, all of UCLA; and Antoniya Aleksandrova and Noah Riley, members of Forrest’s team.

The research was supported by funding from the National Institutes of Health’s Director’s Early Independence Award, Klingenstein-Simons Fellowship Award, and David & Lucile Packard Foundation’s Packard Fellowship for Science and Engineering.

This article originally appeared in the UCLA Newsroom.