How Zika infection changes a human cell

How Zika infection changes a human cell

The Zika virus taking hold of the inner organelles of human liver and neural stem cells has been captured via light and electron microscopy. In Cell Reports researchers show how the African and Asian strains of Zika rearrange the endoplasmic reticulum and cytoskeletal architecture of host cells so that they can build factories where they make daughter viruses. The study reveals that targeting cytoskeleton dynamics could be a previously unexplored strategy to suppress Zika replication.

"Cytoskeleton elements control cellular shape, growth, and movement, provide mechanical support and stress-resilience, and coordinate organelle anchoring and vesicular transport," says senior author. "Zika virus infections cause a drastic perturbation of the cytoskeletal network, re-organizing both intermediate filaments and microtubules into a cage-like structure that surrounds the replication machinery."

The group also found that Zika and dengue, both flaviviruses, use similar strategies to infect host cells. Once inside of a cell, viral particles latch onto the rough endoplasmic reticulum -- the ribosome-rich membranes outside the nucleus where RNA is translated into proteins. The viruses then remodel the endoplasmic reticulum to form a protective cage with small holes where RNA and newly made viral particles can travel in or out.

The difference with Zika is that it has unique ways of rearranging structures within the cell. For example, there are an abundance of microtubules -- proteins that build the cellular cytoskeleton -- surrounding its protective cage. There were also slight variations between how Zika establishes itself in human liver cells versus neural stem cells, where it is more physiologically relevant. This suggests there are yet-unknown cell-type-specific factors that affect how the virus replicates.

Seeing Zika's reliance on the microtubules for its replication, the researchers now want to explore whether these drugs, including taxanes routinely used during chemotherapy, can have potential anti-viral activity against Zika in animal models. These, and similar drugs, have been declared safe to use during the second and third trimester of pregnancy, as well as during breastfeeding.

"Having identified a link between cytoskeleton dynamics and Zika virus replication, together with the plethora of available cytoskeleton-targeting compounds, might contribute to gain mechanistic insight into the ZIKV replication cycle and identify new avenues for treatment," senior author says.