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Scientists ID human protein essential for human cytomegalovirus replication

Protein could serve as potential new drug target

Date:
May 11, 2017
Source:
PLOS
Summary:
Scientists have demonstrated that a human protein known as valosin containing protein (VCP) is essential for replication of human cytomegalovirus (HCMV). The findings identify VCP as a potential new treatment target.
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Scientists have demonstrated that a human protein known as valosin containing protein (VCP) is essential for replication of human cytomegalovirus (HCMV). The findings, published in PLOS Pathogens, identify VCP as a potential new treatment target.

HCMV infects 30 to 100 percent of people worldwide, depending on socioeconomic status. While most remain symptom-free, HCMV can be dangerous or deadly for people with weakened immune systems or for babies infected before birth. Some HCMV treatments exist, but their benefits are limited, and scientists are investigating new ways to treat and prevent infection.

To better understand how HCMV replicates during active infection, Yao-Tang Lin and colleagues at the University of Edinburgh, U.K., performed a search for human genes needed by the virus for replication. They found that reducing the expression of the VCP gene in HCMV-infected human cells significantly reduced viral replication in the cells.

Additional experiments showed that, without VCP, HCMV is unable to express a critical gene known as IE2. This viral gene is known to be essential for replication and is thought to play a major role when the virus switches from symptom-free, dormant infection to active infection.

Given the critical importance of VCP for HCMV replication, the scientists tested the effects of a chemical known to inhibit the activity of VCP. They found that the inhibitor, known as NMS-873, reduced HCMV replication and IE2 expression in infected cells. NMS-873 appeared to be ten times more potent than Ganciclovir, the most commonly used antiviral treatment for HCMV.

Further research is needed to determine whether NMS-873 -- originally developed as a potential anti-cancer drug -- is safe and effective in humans. Nonetheless, these findings suggest that NMS-873 and other molecules designed to inhibit VCP could potentially serve as HCMV treatments, particularly in patients infected with HCMV strains that are resistant to existing drugs.

"Human Cytomegalovirus infection is an important human disease," the authors further explain. "By gaining a better understanding of how the virus works, we can develop improved antiviral drugs. While more work is required, this study shows the potential of such approaches."


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Materials provided by PLOS. Note: Content may be edited for style and length.


Journal Reference:

  1. Yao-Tang Lin, James Prendergast, Finn Grey. The host ubiquitin-dependent segregase VCP/p97 is required for the onset of human cytomegalovirus replication. PLOS Pathogens, 2017; 13 (5): e1006329 DOI: 10.1371/journal.ppat.1006329

Cite This Page:

PLOS. "Scientists ID human protein essential for human cytomegalovirus replication: Protein could serve as potential new drug target." ScienceDaily. ScienceDaily, 11 May 2017. <www.sciencedaily.com/releases/2017/05/170511165353.htm>.
PLOS. (2017, May 11). Scientists ID human protein essential for human cytomegalovirus replication: Protein could serve as potential new drug target. ScienceDaily. Retrieved May 24, 2017 from www.sciencedaily.com/releases/2017/05/170511165353.htm
PLOS. "Scientists ID human protein essential for human cytomegalovirus replication: Protein could serve as potential new drug target." ScienceDaily. www.sciencedaily.com/releases/2017/05/170511165353.htm (accessed May 24, 2017).

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