天花，麻疹，腮腺炎。这些都是欧洲殖民者可能在16世纪之交带到美洲的传染病，导致了土著人口的崩溃。但导致数百万人死亡的确切病毒仍然未知。

　　丹尼尔·布兰科-梅洛试图解开这个历史之谜。作为西雅图弗雷德·哈钦森癌症中心的一名进化病毒学家，他使用尖端工具研究古代病毒，并阐明它们是如何塑造人类进化和历史的。在最近的工作中，布兰科-梅洛和他的同事重建了欧洲殖民时期在墨西哥流行的两种病毒。

　　“我们对古代病毒的研究确实吸引了人们的好奇心，以及我们如何研究历史，”布兰科-梅洛说。但对于在墨西哥出生和长大的布兰科-梅洛来说，这件作品也具有个人意义。通过基因侦查，他能够研究“我心中非常珍视的东西，”他说，“用分子生物学真正理解那些历史事件。”

　　

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　　Viruses shape human evolution

　　Blanco-Melo’s obsession with viruses bloomed in high school when he had a chance encounter with Matt Ridley’s book Genome. Blanco-Melo had bought it as a Father’s Day gift for his dad but ended up reading it himself. Later, with encouragement from his biology teacher, he enrolled in an undergraduate program in genomics at the National Autonomous University of Mexico, or UNAM, campus in Cuernavaca.

　　He had his first encounter with ancient viruses as a Ph.D. student at the Rockefeller University in New York City. His research focused on particular viruses called endogenous retroviruses, remnants of past infectious viruses that have become integrated into a host’s genetic instruction book.

　　Blanco-Melo first cataloged the genetic remains left behind by an ancient retrovirus called HERV-T that spread among our primate ancestors tens of millions of years ago. Further analysis revealed that a gene responsible for producing the virus’s outer envelope stuck around throughout primate history; even modern humans retain an inactive version. This gene encodes the envelope protein that helps the virus enter and infect a cell by interacting with another protein on the cell surface.

　　Why would such a viral gene be so well preserved, Blanco-Melo wondered. What kind of evolutionary advantage could it have offered? based on studies of cells in a lab dish, he hypothesizes that ancient primates must have co-opted the viral gene and used the related protein to get rid of the cell surface protein, essentially blocking the virus’s entry into cells.

　　This example highlights how a virus’s own genetic material, over the course of evolution, can be used against it. “This project not only satisfied my curiosity, but we were able to push it into a full-blown story of how a virus evolved, emerged, but also how that virus ceased to exist,” Blanco-Melo says.

　　Perhaps today’s researchers can exploit similar strategies to combat current retroviruses — “the big goal being HIV,” Blanco-Melo says.

　　Delineating historical events

　　More recently, Blanco-Melo has teamed up with María ávila-Arcos, an evolutionary geneticist at UNAM and an old friend, to study viral epidemics that largely wiped out Indigenous populations in the Americas.

　　Blanco-Melo, ávila-Arcos and a team of researchers extracted and isolated viral DNA from skeletal remains that they dated to somewhere between the 15th and 17th centuries. These remains come from mass graves at a colonial hospital and a chapel in what is now Mexico City. Archaeological and hospital autopsy records suggest that the remains in the graves belonged to Indigenous people and enslaved Africans who were victims of epidemics that occurred during the 1540s and 1570s.

　　based on those findings, the team reconstructed the genetic instruction books of two viruses not previously known to be circulating at that time — human parvovirus B19 and a human hepatitis B virus.

　　The study, published in 2021 in the journal eLife, is perhaps the first to obtain ancient viral sequences from the Americas, says Jesse Bloom, a virologist at the Fred Hutch who wasn’t involved in this work.

　　“Knowing about the ancient viruses that were infecting people hundreds of years ago is of great scientific and historical interestthroughout the world, but especially of interest in the Americas,” Bloom says.

　　The team found that the ancient viruses were similar to contemporary African strains. They “seem to have arrived in Mexico shortly after the European arrival,” Blanco-Melo says, “but they did not come from Europe. They came from Africa, basically through the transatlantic slave trade.”

　　Through the collaboration, Blanco-Melo has been careful to avoid helicopter research, where outsiders come to a place, get the data and take credit for the resulting work. “These samples should stay in Mexico, should be analyzed by Mexican researchers … and all those results are, of course, going to be communicated back into the communities. That’s our goal,” he says.

　　Though the two viruses the team identified aren’t likely to have caused massive epidemics, they could have exacerbated some of the symptoms of other diseases. ongoing projects based on the same samples from Mexico are looking for other viruses and even peptides to get a fuller picture of the viruses from that time — and perhaps pin down big culprits. “There’s a lot more research that needs to be done in order to capture those other causative agents,” Blanco-Melo says.

　　?

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