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Dangerous liaison

Dangerous liaison

作者:安柝峡  时间:2019-03-08 05:19:03  人气:

By Nell Boyce in Washington DC AN ANCIENT virus that invaded the human genome millions of years ago may be an accomplice to HIV, according to a controversial new theory. A biologist says genetic instructions from this “fossil” virus may help HIV evade potent antiviral drugs. Retroviruses such as HIV insert their own DNA into the genome of living cells they infect. Some experts estimate that as much as 1 per cent of the human genome is composed of fossil retroviruses that infected sperm and eggs millions of years ago. Normally these genes lie dormant, but physicians have noticed that they are sometimes expressed in placental tissue and cancerous tumours. Some researchers have also wondered if modern-day retroviruses such as HIV could switch on their fossil cousins. And there are hints—albeit indirect ones—that they can. One study has shown that 70 per cent of people infected with HIV have antibodies to a fossil retrovirus called HERV-K, compared with just 3 per cent of uninfected people. Now Eric Towler of the Science Applications International Corporation in Maryland, a subcontractor to the National Cancer Institute near Washington DC, says he has evidence that HERV-K enzymes may help HIV to evade potent drugs. The idea first came from researchers in Germany who found that HERV-K, like HIV, produces a protease, an enzyme that cuts up long protein chains. Working together, Towler and the German researchers have shown that in the test tube, the ancient protease cuts a long HIV protein at exactly the same spot as the HIV protease. Towler has also found evidence that HERV-K protease can get into HIV in living cells and gets transformed into an active form of the enzyme. “That was a huge surprise,” says Towler. Towler also tested the effects of various anti-HIV protease inhibitors on HERV-K protease. The fossil protease turned out to be highly resistant to all the drugs (Biochemistry, vol 37, p 17 137). He suspects that when HIV protease is inhibited by drugs, HERV-K’s enzyme might take over its work. This could let HIV survive long enough to develop mutations that allow it to resist the drugs’ attack. “This might be part of the whole HIV story,” says Towler. If so, it may be possible to thwart HIV by finding additional protease inhibitors that HERV-K protease can’t resist. However, Tower admits his theory is far from proven: “It’s very much on the fringe—this may very likely be wrong.” Roswitha Loewer, an expert on retroviruses at the Paul Ehrlich Institute in Lange, Germany, says the results are intriguing. “It’s interesting that the HERV-K protease can cleave an HIV sequence,” she says. However, she does not think there is yet compelling evidence that HERV-K is switched on, except in certain tumours: “There are hints, maybe, but no one has really focused on that very thoroughly.” Loewer says that one test could resolve this. If cells that are engineered to express HERV-K protease are infected with HIV that makes faulty protease and the HIV survives nonetheless,