Potential drug target identified for Zika virus

img_0317At a time when no vaccines or therapeutic drugs are available against Zika and other diseases caused by flaviviruses, researchers have successfully found that disabling or silencing one single gene can effectively leave the flaviviruses unable to leave the cell that has been infected, thereby preventing the spread of infection.

Unlike bacteria, viruses must necessarily infect cells to multiply. If, however, the cells lack a gene that the virus requires for infection, the virus cannot get into the cell or infect it.

The results were published on June 17, in the journal Nature.

The researchers performed a genome-wide CRISPR/Cas9-based screen to identify host genes that reduced flavivirus infection when edited. Of the 19,000-odd genes of West Nile virus studied, only nine genes were required for flavivirus infectivity. All of them are associated with an important part of the cell that processes viral particles, which is essential to spreading the infection.

Editing of the nine genes using CRISPR resulted in reduction in West Nile virus antigen expression following infection. The same result was seen in other four diseases caused by flavivirus – Zika, Japanese encephalitis, yellow fever and dengue serotype 2.

As insects transmit pathogenic flaviviruses, scientists studied the orthologues (sequences that have common ancestor and have split due to speciation event) of these genes in insect cells. In fruit fly, silencing the genes reduced the infection of West Nile virus and dengue serotype-2. However, the viability of the cells was not affected.

Of the nine genes studied, Rong Zhang, the first author from the Washington University School of Medicine, Saint Louis, U.S., found that one single gene – SPCS1 – particularly affected flavivirus infection. “Loss of SPCS1 expression resulted in markedly reduced yield” of all five flaviviruses (Zika, West Nile, dengue and yellow fever and Japanese encephalitis) studied.

Despite the huge effect that the SPCS1 gene had on flavivirus protein processing, the expression of host proteins was only “modestly affected” by the absence of the gene, the researchers found.

“Flaviviruses appear to be uniquely dependent on this particular gene to release the viral particle,” senior author Michael S. Diamond from Washington University School of Medicine said no in a release. “In these viruses, this gene sets off a domino effect that is required to assemble and release the viral particle. Without it, the chain reaction doesn’t happen and the virus can’t spread. So we are interested in this gene as a potential drug target because it disrupts the virus and does not disrupt the host infectivity.”

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