Unveiling the Secrets of Rotaviruses: Discoveries by Mexican Virologist Susana López Charretón

Susana López Charretón is among Mexico’s leading virologists. She has been awarded the UNESCO–Carlos J. Finlay Prize for Microbiology and the L’Oréal-UNESCO For Women in Science award. She’s the only female Mexican scientist to have edited the Journal of Virology.

But winning prizes isn’t what inspires her science and her career. “Prizes and recognition are just a consequence,” she says. “Actually, I’m mostly embarrassed by them.”

Instead, it’s curiosity and a thirst for understanding and solving problems that drive her. “To me science is a way of living, something that fulfills me completely,” López Charretón says.

For four decades, she has devoted her life to studying how rotaviruses infect human cells. These double-stranded RNA viruses were described in 1973 by Australian virologist Ruth Bishop and colleagues, when those researchers discovered a virus particle present in the intestinal tissue of children with diarrhea.

Known to cause severe gastroenteritis, including acute diarrhea, vomiting, fever and dehydration, rotaviruses mainly affect babies and small children. Worldwide, the viruses are responsible for the deaths of some 100,000 or more children ages 5 and under every year.

Those numbers used to be more than twice as high. Vaccines, introduced in 2006, dramatically reduced the burden of disease. It was research from a team led by López Charretón and her husband, Carlos Arias Ortiz, along with the work of others around the world, that built the scientific foundation for the development of the vaccines.

López Charretón started studying rotaviruses in the late 1970s, when they were still new to science. “They had just been discovered, so we were able to make important contributions,” she says.

Alongside Arias Ortiz, she defined the multistep processes and the specific molecular players that allow the viruses to invade the cells of the intestine and rapidly replicate their genetic material, the first steps in rotavirus infection and gastroenteritis.“Science is mostly a series of small steps that move knowledge forward,” says Harry Greenberg, an American virologist now retired from Stanford University. “Over the time Susana has been working on rotaviruses, a bunch of vaccines have been made,” he says.

López Charretón knew that she wanted to be a scientist from a young age. As a child, she loved conducting home experiments, like freezing dead flies or opening up dead lizards to explore their insides.

Her mom and dad, unlike most parents of young women at the time, had no problem with her wanting to dedicate her life to studying. With their support, she studied basic biomedical research at the National Autonomous University of Mexico, or UNAM, in Mexico City.

López Charretón’s tutor, Romilio Espejo, a Chilean virologist who had moved to Mexico, was studying rotaviruses and introduced her to them. She became increasingly fascinated by their complexity and wanted to understand them. “Rotaviruses cause very serious problems in the world,” she says.

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Around that time, López Charretón also met Carlos Arias, who was doing a master’s degree in Espejo’s lab. She stayed on at UNAM for a master’s degree and Ph.D., and she and Carlos Arias went to California from 1981 to 1983 for a research sabbatical in the Caltech laboratory of biologist James Strauss. There, they continued the work they had begun with Espejo. “This was my path to realize that virology was what most interested me,” she explains.

Back in Mexico, the couple formed a research group at the Institute of Biotechnology at UNAM and continued to study rotaviruses. At the time, most scientists thought rotaviruses invaded cells in a relatively simple process, with just one viral protein interacting with one cell receptor.

Instead, the group showed, rotavirus entry into a host cell is mediated by multiple steps and interactions with the surface of the cell. These steps take place in a specific part of the cell’s plasma membrane known as lipid rafts and end with the virus entering through endocytosis, a cellular process in which a substance is surrounded by an area of the cell’s membrane to form a vesicle that transports the substance into the cell.

López Charretón’s group also described the molecules that help rotaviruses beat the body’s innate antiviral system. Two viral proteins that play multiple roles directly interact with the cells of the intestine and prevent the antiviral response. This finding could explain why the viruses are so specific in the cells they infect.

Theirs is now the prevailing model describing how rotaviruses invade cells. “All viruses establish these types of battles with their host cells, and the amazing part is that each virus has different tools to do it,” López Charretón says.

López Charretón continues to work on rotaviruses, trying to figure out how they pervert the entire cellular machinery within intestinal cells. But in the early days of the COVID-19 pandemic, she was part of a group of virologists charged with monitoring and sequencing the coronavirus strains circulating in the country.She and other virologists founded the multi-institutional Genomic Surveillance Consortium of Mexico. Though the group planned to continue monitoring other viruses following the pandemic, it has disbanded because of a lack of financial support from the government.

The effort emphasized for López Charretón the importance of growing Mexico’s pool of scientists. “With the pandemic, it became obvious that we don’t have enough people who are experts in virology in order to face these types of problems,” she says.

She has worked to build that scientist pipeline throughout her career, by helping to train young virologists who are just as driven as she is. “[As a scientist,] you also have the joy of sharing your passion with your students, watching them grow and becoming very rigorous in their craft,” she says.

Besides being a leading scientist, says Greenberg, one of López Charretón’s most outstanding traits is her willingness to teach. Three of her students have gone on to do postdocs in Greenberg’s lab. He has observed how close they are to her and how well trained they are; he says she’s probably the most caring and attentive mentor he has ever met.

Liliana Sánchez Tacuba, who did a Ph.D. with López Charretón before moving on to Greenberg’s lab for a postdoc, agrees that, unlike a lot of lab leaders, López Charretón makes time to dedicate herself to teaching. “I couldn’t have had a better tutor,” Sánchez Tacuba says. “She is my academic mom and every time I have difficulty or doubts, I still contact her.”Sánchez Tacuba comes from a small, low-income community in the state of Guerrero, Mexico, where most women study only through primary school. Today, she is a research scientist in the microbiology division at Vir Biotechnology, an American immunology company focused on treating and preventing infectious diseases.

All of this was possible because of López Charretón, Sánchez Tacuba says, and the time and effort López Charretón dedicated to mentoring her. “She changed my life,” Sánchez Tacuba says. “Every time I’ve second-guessed myself, I’ve thought that if Susana López believes in me, then I must be able to do it.”

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