Menneskelig modstand mod et retrovirus, som inficerede chimpanser og andre ikke-humane primater for 4 millioner år siden kan, ironisk nok, være i det mindste delvist ansvarlig for menneskers følsomheden ​​ overfor HIV-infektion i dag.

Disse fund er indberettet af et team af forskere ved Fred Hutchinson Cancer Research Center i 22. juni-udgaven af ​​Science og giver en bedre forståelse af denne moderne pandemiske infektion gennem undersøgelsen af ​​en gammel virus kaldet Pan troglodytes endogen retrovirus eller PtERV1.

"Denne gamle virus er en kamp, ​​som mennesker allerede har vundet. Mennesker er ikke modtagelige for den og har sandsynligvis været resistente gennem årtusinder," sagde seniorforfatter Michael Emerman, Ph.D., medlem af Human Biology and Basic Sciences afdelingen ved Hutchinson Center. "Vi fandt imidlertid, at under den primite udvikling kunne denne medfødte immunitet mod en virus have gjort os mere sårbare over for HIV."

Bevis for menneskelig immunitet over for dette gamle retrovirus fremkom først med sekventeringen af ​​chimpansegenet. "Da chimpansegenomet blev sekventeret, fandt et team af videnskabsfolk ved University of Washington ledet af Evan Eichler den største forskel samlet set mellem chimpansen og det humane genom var tilstedeværelsen eller fraværet af PtERV1,'" sagde Emerman. "Chimpanser har 130 kopier af PtERV1, og mennesker har ingen."

Det antages, at retrovirus er kommet ind i genomet gennem mange millioner år, og derfor deler mennesker mange retrovirale DNA-fragmenter med deres primatfætter. Sådanne rester af primitiv infektion, der gøres inaktive af æoner af genetisk mutation, udgør ca. 8 procent af det menneskelige genom.


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Innate protection against PtERV1 in humans could be credited, the researchers believe, to the presence of an ancient, rapidly evolving antiviral defense gene called TRIM5a, which produces a protein that binds to and destroys the virus before it can replicate within the body.

"We know that PtERV1 infected chimps, gorillas and old-world monkeys 4 million years ago but left no traces of having infected humans. Our theory is that this is because humans had this innate viral defense system," Emerman said.

To test their hypothesis, Emerman and co-authors Harmit Singh Malik, Ph.D., an evolutionary biologist and an assistant member of the Center's Basic Sciences Division, and Shari Kaiser, a graduate student in Emerman's laboratory, used DNA sequences from the chimp genome to reconstruct a small part of the PtERV1 virus.

They reassembled about one-fifth of the virus by taking dozens of PtERV1 sequences and aligning them to create an "ancestral" sequence, teasing out areas of commonality between them. They then used this information to make a partial viral genome. During reconstruction the viral segment was debilitated, enabling only one round of infection in cells. Working with cells in the laboratory, the researchers found that the human antiviral protein TRIM5a effectively neutralizes this extinct retrovirus, which never successfully fixed into the human genome.

"However, while TRIM5a may have served humans well millions of years ago, the antiviral protein does not seem to be good at defending against any of the retroviruses that currently infect humans, such as HIV-1," Emerman said. "In the end, this drove human evolution to be more susceptible to HIV." For example, the researchers found that changes in TRIM5a that make it better at fighting HIV actually inhibit its ability to stop PtERV1 and vice versa, which indicates that this antiviral gene may only be good at fighting off one virus at a time.

Uncovering the story of TRIM5a's role in battling one ancient retrovirus while increasing human susceptibility to modern-day HIV "is a lot like doing archaeology -- figuring out how humans have become who we are today and why we are or are not susceptible to modern viruses that presently circulate," Emerman said.

In fact, this emerging area of research, which seeks to better understand modern infections by studying ancient viruses, is known as "paleovirology." "Ultimately," said co-author Malik, "if we want to understand why our defenses are the way they are, the answers inevitably lie in these ancient viruses more so than the ones that have affected us only recently, such as HIV."