MAY 17, 2017 08:06 AM PDT

New target for treating HCMV

WRITTEN BY: Kerry Evans
2 4 408

Researchers at the University of Edinburgh’s Roslin Institute identified a host-cell molecule that helps the human cytomegalovirus (HCMV) to replicate.

HCMV is a herpesvirus - it was first described by the German pathologist Hugo Ribbert in 1881. The prefixes cyto (cell) and megalo (large) refer to the fact that infected cells are quite large. HCMV infects around 30% of people in developed countries, but it infects nearly 100% of people in the developing world. While HCMV is relatively harmless to healthy people, the infections can be serious for people who are immunocompromised or have heart disease. It can also cause hearing loss and intellectual disabilities in unborn babies.

HCMV is a herpesvirus -Labiotech

HCMV infection is usually associated with the salivary glands, and it can cause mucoepidermoid carcinoma (and possibly prostate cancer). In the immunocompromised, HCMV can cause hepatitis, colitis, pneumonitis, or esophagitis. It’s not entirely clear how HCMV is transmitted from person to person, but transmission likely occurs through body fluids.

The researchers used an siRNA screen to identify host factors that are important for HCMV replication and found that VCP is essential. VCP (valosin-containing protein) is important for ubiquitin-mediated signaling in the host cell; VCP is an ATPase that generates energy to modify its target proteins.

They verified their findings with siRNA that specifically targeted VCP. Primary human fibroblasts were infected with HCMV that produces green fluorescent protein (GFP). When the infected cells expressed siRNA specific for VCP, the viral titers were over 4 logs lower than in control cells, and no viral replication was observed.

VCP is actually targeted by many cancer drugs, so they determined if small-molecule inhibitors of VCP could inhibit HCMV replication. They treated the cells with the VCP inhibitor NMS-873 or DMSO and infected them with HCMV. Like the VCP siRNA, NMS-873 decreased viral gene transcription and protein expression.

Finally, they tested NMS-873 against the antiviral drug Ganciclovir, which is commonly used to treat HCMV. They pretreated fibroblasts with Ganciclovir, NMS-873, or DMSO and then infected them with HCMV. Both Ganciclovir and NMS-873 inhibited viral replication, but NMS-873 was effective at a ten-fold lower concentration than Ganciclovir.

According to study author Finn Grey, “Human Cytomegalovirus infection is an important human disease. 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."

Sources: PLOS Pathogens, Science Daily, Wikipedia


About the Author
  • Kerry received a doctorate in microbiology from the University of Arkansas for Medical Sciences.
You May Also Like
JUL 04, 2018
Drug Discovery
JUL 04, 2018
Discovery of New Properties of an Anti-Tuberculosis Drug
  Investigators at the University of Otago found novel properties of a new anti-tuberculosis drug which may inspire more new drugs to treat tuberculos
JUL 16, 2018
JUL 16, 2018
Cyclospora to Blame for Several Foodborne Outbreaks
One outbreak of cyclosporiasis, which is caused by a parasite, has been traced back to salads sold at McDonald's, mostly in the Midwest.
JUL 18, 2018
Genetics & Genomics
JUL 18, 2018
Shedding Light on a Genomic Mystery
There are untold numbers of bacteria in our world, and we play host to trillions of microbes. So what are all those bacterial genes doing?
JUL 19, 2018
JUL 19, 2018
HIV Infection Doubles Risk of Heart Disease
Recent study of 150 countries and over 800,000 people shows HIV patients are more than twice as likely to develop Heart Disease than uninfected individuals.
AUG 02, 2018
AUG 02, 2018
Chronic Infections Outsmart the Immune System
Chronic parasitic infection shown to take advantage of a mechanism to sustain infection and induce death of white blood cells essential to immune response.
AUG 02, 2018
AUG 02, 2018
As Earth Warms, Soil 'Breathes' Harder
Temperatures are on the rise, and it seems soil will become another factor in how our climate changes.
Loading Comments...