Novel target for the intervention of HCMV infection
A team headed by Nicholas Buchkovicha at Pennsylvania State University College of Medicine has developed a compound to combat human cytomegalovirus (HCMV), a species of the Cytomegalovirus genus of viruses.
In the normal population, HCMV usually causes little or no disease. But in newborns, immunocompromised individuals, or patients on immune suppressive therapies, the virus can cause severe disease and even death. Currently available drugs may lead to unwanted side effects, and the virus is able to mutate to avoid being killed by these drugs.
In the paper published in the Journal of Virology, Buchkovicha and colleagues describe that a Retro94-based compound prevents HCMV from making copies of itself.
How HCMV infects a cell and reproduces is not well understood. But it is known that the cytoplasmic viral assembly compartment (cVAC) is the place where new viral particles are assembled. Buchkovicha wondered which cellular factors contribute to the formation of cVAC.
Buchkovicha's team identified a cellular protein, syntaxin 5, that is elevated in CMV-infected cells. The protein seemed to be involved in cVAC formation and critical for the efficient production of infectious virions.
Using the miRNA knockdown technique, Buchkovicha's team found that reducing Syntaxin 5 caused the cVAC to have irregular shapes and to be less able to produce new viral particles.
A small molecule called Retro94 is known to disrupt Syntaxin 5. Buchkovicha's team designed a Retro94-based compound. Laboratory experiments showed that the compound suppressed the formation of the cVAC and then decreased the production of HCMV. The results suggested Syntaxin 5 as a novel target for intervention of HCMV infection.
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