Zika virus: new techniques reveal potential gene suppression mechanism in macrophages

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A recent study, utilizing new research methods, has demonstrated how Zika virus may suppress gene transcription reducing immune response in human macrophage cells.

In a study published recently in the Proceedings of the National Academy of Sciences, a team of scientists reported their findings on how the Zika virus (ZIKV) affects transcription in infected cells. These changes engendered a reduction in gene production causing reduced immune response and loss of cell identity.

The team, led by Aaron Carlin Christopher Glass (both University of California San Diego School of Medicine; CA, US) and Sujan Shresta (La Jolla Institute for Allergy and Immunology; CA, USA), utilized a novel technique to both identify and isolate ZIKV infected human macrophage cells from a mixed sample in order to obtain more detailed evidence of gene suppression activity by ZIKV.

This was crucial to the study as acquiring data from a mixed population can reduce the validity of any results obtained. Additionally, this allowed for valuable comparison between the two populations. The team found the results of comparing gene production to be unexpectedly disparate between uninfected and infected cells.

“We were surprised at just how different infected and uninfected cells looked, in terms of the genes they had turned on or off, even two cells next to each other,” Glass commented. “What’s amazing is that even though they are exposed to the same environment, their responses are completely different. And now we know those differences are truly due to the virus, not any of the other events going on around the cells during an immune response.”

ZIKV suppressed genes within the macrophages in both those responsible for I IFN response and for RNApolII, for instance levels of expression of IFITM1 were reduced in infected cells by a factor of 73. This resulted in a loss of gene production both generally and specifically for immunity, as well as a loss of identity in the infected macrophages.

This may have implications within other types of cell such as neonatal neurons, and could provide an explanation for the causes behind microcephaly in infants infected by mother-to-fetus vertical transmission.

Carlin explained: “We know Zika virus destroys a number of cell types, particularly in the brain, but we don’t yet understand how it causes cells to die or malfunction. So this loss of general gene transcription and identity we saw in macrophages could also be crucial when a neural stem cell is trying to develop into a new neuron.”

The team is hoping to apply these methods to further research the effects of other viruses, as well as demonstrate the effect of ZIKV on other cells, such as human neural stem cells.

Sources: Carlin AF, Vizcarra EA, Branche E et alDeconvolution of pro- and antiviral genomic responses in Zika virus-infected and bystander macrophagesProceedings of the National Academy of Sciences doi: https://doi.org/10.1073/pnas.1807690115 (2018) (Epub ahead of print); https://health.ucsd.edu/news/releases/Pages/2018-09-10-zika-virus-strips-immune-cells-of-their-identity.aspx

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