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Cytomegalovirus infection process in humans

Human cytomegalovirus (HCMV) belongs to the enveloped herpes virus family and is associated with cancer and deterioration of the immune system due to poor treatment options. The EU-funded SHERPA project aims to unravel the process by which viral membrane proteins act as fusion machineries and cause infection in human cells.
Cytomegalovirus infection process in humans
The fusion machinery of HCMV is highly complex, involving type I transmembrane glycoprotein B (gB) and gH/gL complexes that has made dynamic molecular modelling difficult. gB proteins help in membrane merging while gH/gL complexes provide ancillary functions.

Members on the 'Structure of herpesviral cell access' (SHERPA) project will investigate gB structure involved in membrane merging using X-ray diffraction to study the structure of crystallised viral players. This will unravel the mechanics of HCMV entry into the host cell and identify HCMV fusion inhibitors.

Project members developed, for the first time ever, a biochemical quality production method of a herpes virus gB fusion factor form that enabled protein-folding analysis. Future studies could elucidate the mechanism by which this viral protein enters target cells in humans and evades human immune system response. Anti-CMV subunit vaccine candidates were also successfully developed.

SHERPA successfully shed some light on the HCMV fusion machinery. HCMV is a leading infectious cause of congenital brain defects and life-threatening complications in transplant recipients and immunodeficient individuals.

Current anti-HCMV drugs are ineffective and highly toxic, necessitating the discovery of alternative viral targets to develop novel therapeutic strategies. Future research work can build on SHERPA findings to find novel therapeutic strategies to deal with HCMV infections.

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