More than 80 percent of human immunodeficiency virus (HIV) infections are transmitted via sexual intercourse. And researchers may have discovered at least one reason why. According to a new study published in Cell, a component of human semen may facilitate the spread of the virus by targeting immune system cells, in some cases making the pathogen up to 100,000 times more virulent.
The team of German scientists had initially set out to determine if semen contained factors that inhibit the HIV infection. "We were not expecting to find an enhancer, and we were even more surprised about the strength," says report co-author Frank Kirchhoff, a virologist at the University of Ulm Clinic in Germany. "Most enhancers have maybe a two- or three-fold effect, but here the effect was amazing—more than 50-fold and, under certain conditions, more than 100,000-fold."
HIV, the virus that leads to AIDS, has infected 60 million people worldwide (causing 25 million deaths) since it was discovered in humans in 1981. The transmission rate from intravaginal sexual intercourse is estimated at one in every 200 to 2,000 acts. In Africa, 60 percent of new infections are in women who have had sex with HIV-positive men.
Kirchhoff and his team screened through many of the 900 proteins found in seminal fluid in their hunt for potential inhibitors and enhancers of HIV transmission. Among the enhancing factors uncovered were fragments of a protein called prostatic acid phosphatase that is secreted by the prostate gland. An analysis of the peptide's structure in semen indicated that it hooked up with similar fragments to create amyloid fibers (clusters of protein fragments that have also been implicated in diseases such as Alzheimer's). The scientists refer to the amyloid fibers as "semen-derived enhancer of virus infection" (SEVI). If they do not link to become fibers, the researchers report, the peptide segments remain inactive and do not enhance viral transmission.
When assembled, however, these fibers then act like ferries, trapping and shuttling HIV virus particles to target cells. The researchers found that HIV spiked into semen was more successful than the virus alone at infecting T cells and macrophages (immune system cells that are believed to be the infection's initial targets in the body). They also tested the threshold of virus needed to infect human tonsil cells, noting that in the presence of semen, far fewer HIV particles were needed for transmission.
Researchers injected both the naked virus and SEVI-treated HIV into the tails of rats that had been given human immune system cells. The HIV with the semen component was five times more effective at transmitting the virus. In situations where low levels of virus are transferred—as during intercourse—Kirchhoff says, SEVI can make HIV up to 100,000 times more likely to spread when compared with the virus alone.
In an editorial accompanying the article, postdoctoral fellow Nadia Roan, along with Warner Greene, a senior investigator at the University of California, San Francisco's Gladstone Institute of Virology and Immunology, wrote: "If SEVI truly increases the real world heterosexual spread of HIV by several orders of magnitude, then negating the activity of this factor could conceivably diminish these frequencies to levels that might virtually eliminate semen-driven HIV transmission."
But, others say more work is needed to fully comprehend the role of prostatic acid phosphatase in viral transmission. "I don't think you can really make any interpretation of that experiment other than it makes the virus more infectious if it reaches target cells … which is very difficult across mucosal surfaces," says Robin Shattock, a professor of cellular and molecular infection at St George's, University of London. The sentiment is echoed by Myron Cohen, an epidemiologist at the Center for Infectious Diseases at the University of North Carolina School of Medicine in Chapel Hill: "We need to understand every detail about the biology of HIV transmission…; the [next] logical experiments are to demonstrate in rhesus macaque models that this is playing a role in transmission."
有了宝宝，生命才算有了
首届中国（西南）男性健
三鹿集团“十·一”居然
80%以上的人类免疫缺陷症感染是通过性接触传递的，研究者可能已经发现至少一条原因来支持它。根据一项刊登在CELL上的新研究表明，人类精液中有种成分也许会通过琐定免疫系统细胞而促使HIV的扩散，在一些情况下使得传染源的烈性达到原来的100000倍。
一组德国科学家已经开始着手推断是否精液里含有一些因子能够抑制HIV的传染。据德国的Ulm临床大学通讯合作作者Frank Kirchhoff说：“我们没有期望能找到一个促进因子，我们甚至更惊奇他们的力量，”多数促进因子可以使得作用提高2到3倍，但是在这里这种作用很神奇，能提高50倍，在特定情况下，多余 100000倍。
从1981年这个病毒被发现，在全世界，HIV已经使得全球60万人(其中有25万人死亡)。阴道内性接触的传播率被认为是从1/200到1/2000。在非洲，60%的新感染是在那些与HIV阳性男人做爱后的妇女。
Kirchhoff和他的团队通过对精液中900种蛋白质进行筛选来寻找潜在的控制HIV传播的抑制因子和促进因子。在揭晓的促进因子中，有些是一种叫做前列腺酸性磷酸酶的片段，这种蛋白质是由前列腺分泌的。精液中的肽结构分析表明这种片段与相似一种相似的片段连接在一起可以产生一种淀粉纤维(一段与阿滋海默症有关的蛋白片段)。科学家们把这种淀粉纤维称作“病毒感染的精液驱动促进因子”(SEVI)。研究者表明，如果它们不连接形成纤维，肽片段不会受到影响，并且不会促进病毒传染。
【附】原文如下：
Male Semen Makes HIV More Potent
More than 80 percent of human immunodeficiency virus (HIV) infections are transmitted via sexual intercourse. And researchers may have discovered at least one reason why. According to a new study published in Cell, a component of human semen may facilitate the spread of the virus by targeting immune system cells, in some cases making the pathogen up to 100,000 times more virulent.
The team of German scientists had initially set out to determine if semen contained factors that inhibit the HIV infection. "We were not expecting to find an enhancer, and we were even more surprised about the strength," says report co-author Frank Kirchhoff, a virologist at the University of Ulm Clinic in Germany. "Most enhancers have maybe a two- or three-fold effect, but here the effect was amazing—more than 50-fold and, under certain conditions, more than 100,000-fold."
HIV, the virus that leads to AIDS, has infected 60 million people worldwide (causing 25 million deaths) since it was discovered in humans in 1981. The transmission rate from intravaginal sexual intercourse is estimated at one in every 200 to 2,000 acts. In Africa, 60 percent of new infections are in women who have had sex with HIV-positive men.
Kirchhoff and his team screened through many of the 900 proteins found in seminal fluid in their hunt for potential inhibitors and enhancers of HIV transmission. Among the enhancing factors uncovered were fragments of a protein called prostatic acid phosphatase that is secreted by the prostate gland. An analysis of the peptide's structure in semen indicated that it hooked up with similar fragments to create amyloid fibers (clusters of protein fragments that have also been implicated in diseases such as Alzheimer's). The scientists refer to the amyloid fibers as "semen-derived enhancer of virus infection" (SEVI). If they do not link to become fibers, the researchers report, the peptide segments remain inactive and do not enhance viral transmission.
When assembled, however, these fibers then act like ferries, trapping and shuttling HIV virus particles to target cells. The researchers found that HIV spiked into semen was more successful than the virus alone at infecting T cells and macrophages (immune system cells that are believed to be the infection's initial targets in the body). They also tested the threshold of virus needed to infect human tonsil cells, noting that in the presence of semen, far fewer HIV particles were needed for transmission.
Researchers injected both the naked virus and SEVI-treated HIV into the tails of rats that had been given human immune system cells. The HIV with the semen component was five times more effective at transmitting the virus. In situations where low levels of virus are transferred—as during intercourse—Kirchhoff says, SEVI can make HIV up to 100,000 times more likely to spread when compared with the virus alone.
In an editorial accompanying the article, postdoctoral fellow Nadia Roan, along with Warner Greene, a senior investigator at the University of California, San Francisco's Gladstone Institute of Virology and Immunology, wrote: "If SEVI truly increases the real world heterosexual spread of HIV by several orders of magnitude, then negating the activity of this factor could conceivably diminish these frequencies to levels that might virtually eliminate semen-driven HIV transmission."
But, others say more work is needed to fully comprehend the role of prostatic acid phosphatase in viral transmission. "I don't think you can really make any interpretation of that experiment other than it makes the virus more infectious if it reaches target cells … which is very difficult across mucosal surfaces," says Robin Shattock, a professor of cellular and molecular infection at St George's, University of London. The sentiment is echoed by Myron Cohen, an epidemiologist at the Center for Infectious Diseases at the University of North Carolina School of Medicine in Chapel Hill: "We need to understand every detail about the biology of HIV transmission…; the [next] logical experiments are to demonstrate in rhesus macaque models that this is playing a role in transmission."
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译者：我佛横刀
编辑：医圣之慈悲天下
来源：Scientific American网站