To protect humans against infection, a protein called MARCH8 tags the vesicular stomatitis virus (VSV) for destruction while it merely holds HIV hostage, a new study in eLife shows.
The findings reveal how a single protein can use multiple strategies to defend cells against viral infection. They could also improve our understanding of how HIV overcomes the human immune defence.
Previous studies have shown that MARCH8 stops HIV and VSV from entering human cells by targeting the viral proteins that are essential for these viruses to enter cells. But how the protein does this remained unclear. Researchers in Japan suspected that MARCH8 might flag an important VSV envelope protein for destruction by targeting a particular amino acid called lysine.
The VSV G-glycoprotein (VSV-G) has a short tail containing five lysines, making it an ideal target. The HIV envelope glycoprotein (Env), by contrast, has a very long tail with only two lysines, making it harder for MARCH8 to flag it for destruction.”
Kenzo Tokunaga, Senior Author, Principal Investigator in the Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan
To test their idea, Tokunaga and his team, including co-first authors and Postdoctoral Fellows Yanzhao Zhang and Takuya Tada, replaced the five lysines on the tail of VSV-G with five arginines – another type of amino acid. They also replaced the two lysines on the tail of HIV Env with two arginines. The change allowed VSV-G to escape MARCH8, but not HIV Env. This suggests that MARCH8 targets HIV Env and VSV-G using two different mechanisms.[…]