猴子基因, Mice Could Work as Antiviral to Block 艾滋病毒, 埃博拉病毒 in Humans

A nationwide team of researchers, led by scientists at 大发娱乐 and The Rockefeller University, has determined how a genetic mutation found in 老鼠 and monkeys interferes with viruses such as 艾滋病毒 and 埃博拉病毒. They say the finding could eventually lead to the development of medical interventions in humans 

的基因, 叫retroCHMP3, encodes an altered protein that disrupts the ability of certain viruses to exit an infected cell and prevents it from going on to infect other cells.

正常情况下, some viruses encase themselves in cell membranes and then make an exit by budding off from the host cell. RetroCHMP3 delays that process long enough that the virus can no longer escape.

“This was an unexpected discovery,” 奈尔斯·埃尔德博士.D., senior author of the study and an evolutionary geneticist in the Department of Human Genetics at U of U Health. “We were surprised that slowing down our cell biology just a little bit throws virus replication off its game.”

The study appears online Sept. 在10月30日之前. 第十四期 细胞.

RetroCHMP3 originated as a duplicated copy of a gene called charged multivesicular body protein 3, 或CHMP3. 而有些猴子, 老鼠, and other animals have retroCHMP3 or other variants, humans only have the original CHMP3.

在人类和其他生物中, CHMP3 is well known for playing a key part of a role in cellular processes that are vital for maintaining cellular membrane integrity, 细胞间的信号, 细胞分裂.

艾滋病毒 and certain other viruses hijack this pathway to bud off from the cellular membrane and infect other cells. 根据他们的研究, Elde and his colleagues suspected that the duplications of CHMP3 they discovered in primates and 老鼠 blocked this from happening as protection against viruses like 艾滋病毒 and other viral diseases.

以这个概念为基础, Elde and other scientists began exploring whether variants of retroCHMP3 might work as an antiviral. In laboratory experiments conducted elsewhere, 更短的, altered version of human CHMP3 successfully prevented 艾滋病毒 from budding off cells. But there was a glitch: the modified protein also disrupted important cellular functions, 导致细胞死亡. 

不像其他研究人员, Elde and his colleagues at U of U Health had naturally occurring variants of CHMP3 from other animals in hand. So, working in collaboration with researchers Sanford Simon at The Rockefeller University, along with Phuong Tieu Schmitt and Anthony Schmitt at Pennsylvania State University, they tried a different approach.

使用基因工具, they coaxed human cells to produce the version of retroCHMP3 found in squirrel monkeys. 然后, they infected the cells with 艾滋病毒 and found that the virus had difficulty budding off from the cells, essentially stopping them in their tracks. And this occurred without disrupting metabolic signaling or related cellular functions that can cause cell death.