The human immunodeficiency virus that causes AIDS has such complex interactions with the human immune system that it has driven scores of discoveries in the fields of immunology and vaccine design.
This research has gone on for the most compelling of reasons: some
85.6 million people have become infected with HIV, according to the Joint United Nations Programme on HIV/AIDS, and approximately 40.4 million people have died from AIDS-related illnesses since the start of the epidemic.
Los Alamos National Laboratory, in addition to its more well-known fields of research, has had a long history of studying the vast diversity of genetic sequences of all kinds, thanks to early 1980s visionaries such as Walter Goad and George Bell, physicists at the Lab who recognized that genetic code in DNA was similar to the binary code on which all computers run. They developed the first database to store the huge array of genetic sequences that was beginning to accrue globally, establishing GenBank, a single repository for all DNA sequences.
In 1983, HIV was identified as the cause of AIDS. Gerald Myers, a
St. John’s College professor who also worked with the GenBank files at Los Alamos, recognized the extraordinary diversity of the first few HIV isolates, and the value of a pathogen-specific database to store HIV’s genetic sequences became clear. In 1986, he founded the HIV Sequence Database at the Lab. The HIV Sequence Database became the first repository of gene sequences associated with a specific virus. Myers clearly foresaw that this virus would present new challenges in the fields of virology and vaccine design. Suddenly, Los Alamos was connected to the world of HIV research and rapidly building its reputation in that field thanks to its deep familiarity with the challenges of handling the complexity of extracting information from enormous data files.
Keenly interested in evolution, Myers led many studies identifying the rapid evolution of HIV in the human population and understanding its place among various viruses found in African primate species, such as chimpanzees and sooty mangabeys. Within a single HIV-infected human patient, sampled over several years between initial infection and development of AIDS, relatively large viral evolutionary changes revealed themselves. The battle within the body, documented in the viral genetic sequences stored in the database, was fierce, as the human immune system fought the virus and researchers observed the virus evolving to escape each new battle. In the field of evolutionary study known as phylogenetics, this was groundbreaking stuff.
When Los Alamos theoretical biologist Bette Korber joined the Lab’s HIV Sequence Database team in 1990, she initially helped by using her experience in viral sequencing and evolution to support the team’s effort. But her doctorate was in immunology, which led her to propose a whole new resource, an HIV Immunology Database to complement the HIV Sequence Database. The immunology database — the first pathogen-specific immunology database — catalogs and aids understanding of how the human immune system interacts with HIV. In 1994, Myers passed the leadership of both database projects on to Korber, and she went on to lead the database team in creating online, interactive, searchable databases with many analysis tools that researchers can use directly through the internet.
This is where I come in. I joined the Los Alamos team in 1995 as a virologist and epidemiologist with skills in computer science. Through the project, I’ve worked with experimentalists from all over the globe. In 2020 — as the pandemic gained momentum — Korber passed the leadership of the database projects to me so she could concentrate on tracking COVID-19 evolution.
The databases have been continuously funded by the National Institutes of Health’s National Institute of Allergy and Infectious Diseases since 1988 and was once described by Anthony Fauci as “the biggest bang for the buck in all of the NIH.”
The databases now serve more than 10,000 unique website visits per month from researchers located throughout the world. The database team has also taken on other viruses such as hepatitis C virus, Ebola and influenza, which have grown and since been passed on to other groups.
The value the HIV sequence and immunology databases have brought to researchers internationally is particularly rewarding. Almost every day, new research papers are published around the world noting the use of the Los Alamos databases for studies ranging from new vaccine approaches to understanding how the virus behaves and changes within its victims. The global impact of the databases is a dramatic testament to the resources a national laboratory can bring to complex, multidisciplinary challenges.
Our work with HIV has allowed us to make major contributions to vaccine design, rapid diagnostic test design, epidemiology and other aspects of not only HIV, but also other important viruses, including the virus causing COVID-19. Early in the pandemic, those of us involved in the care and feeding of the HIV databases were all too aware of how the SARS-CoV-2 virus could spread around the world and mutate into new lineages. It’s a story we’ve seen before, in the viruses behind hepatitis C, HIV and other diseases we study. In some ways, the evolution of the SARS-CoV-2 virus across the planet’s whole human population emulates the way the HIV virus evolves within a single infected human. We hope that the work at Los Alamos will continue to benefit the world’s population as these viruses challenge us all.
