ZIKV uses exosomes that contains virus RNA and proteins as mediators of viral transmission between neurons. Exosomes derived from neuronal cells infect naïve cells in a time- and dose-dependent manna. Furthermore, ZIKV infection induced both activity and gene expression of neutral Sphingomyelinase (nSMase)-2/SMPD3, an important molecule that regulates production and release of exosomes. Silencing of SMPD3 in neurons resulted in reduced viral burden and transmission through exosomes. Treatment with SMPD3 specific inhibitor GW4869, significantly reduced ZIKV loads in both cortical neurons and in exosomes derived from these neuronal cells. Taken together, ZIKV modulates SMPD3 activity in cortical neurons for its infection and transmission through exosomes perhaps leading to severe neuronal death that may result in neurological manifestations such as microcephaly in the developing embryonic brains.
Investigated a new mechanism of how ZIKV could infect naive cells through exosomes and provided a new insight of protection and inhibition of viral infection. Sphingomyelinase could also be a targeted molecule to prevent viral infection and a strategy of viral drug.
For more viral exosome references, please check PLOS pathogens and PNAS papers of Wenshuo ZhouDr wenshuo-zhou, Ph.D
Emerg Microbes Infect 2019 ;8(1):307-326
a Department of Biological Sciences, Center for Molecular Medicine , Old Dominion University , Norfolk , VA , USA.
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