ZIKA VIRUS AS A THERAPY FOR GLIOBLASTOMAS

MURILO HIGA CIMATTI DE ANDRADE KRATZ, BRENDA BARZOTTO ARNOLD, CAIO CEZAR ESQUEAPATTI SANDRIN, SALVADOR DIAS VIEIRA NETO

Resumo


Introduction: Glioblastomas (GB) are the most common malignant Central Nervous System (CNS) tumors, as well as the most lethal1. They have a diverse morphological organization and high mitotic activity, resulting in a fast growth. Despite the chemotherapy, radiotherapy and surgical treatments available, these tumors generally have a grim prognosis1. Recently, though, a new discovery unveiled an oncolytic property in the Zika Virus (ZIKV), opening a new possibility for more efficient therapy against GB. Objectives: This work aims to discuss some recent findings that point to the Zika virus as a therapeutic potential against glioblastomas. Methods: A literature review was conducted during the month of September 2017 in the databases of PubMed and Lilacs, with the following keywords: glioblastoma and zika. Discussion: ZIKV is a flavivirus, from the Flaviviridae family, transmitted by mosquitoes of the genus Aedes2. It is known to be a trigger of Guillain-Barret Syndrome and there is evidence of causality between ZIKV and congenital neurological and ophthalmological abnormalities2. However, the full spectrum of neurological complications and the long-term sequelae of ZIKV infection remain to be determined2. More than that, the neurotropism of ZIKV could be a possible therapeutic for CNS cancers. Researchers hypothesized that, since the ZIKV infect neuroprogenitor stem cells in developing brain, leading to loss of proliferation and cell death, it could be used against GB3. First, they infected differentiated glioma cells (DGCs) and glioblastoma stem cells (GSCs) with ZIKV in vitro3. The virus had as its preferred target the GSC, decreasing their formation and increasing apoptosis; otherwise the DGC were almost unaffected3. Then, to test the oncolytic activities of ZIKV in vivo, researchers inoculated a mouse-adapted ZIKV-Dakar strain on gliomas induced in mice3. The virus led to regression of the tumor, prolonged survival of the animals and it had marginal effects on their CNS cells3. Comparing to other viruses that have been studied in the last decades as potential antineoplastic agents, such as West Nile virus, also a flavivirus transmitted by Aedes, the ZIKV has been proved to be more efficient against the tumor tissue and safer, as it is less toxic to normal brain cells3,4. Conclusion: The Zika virus has attracted worldwide attention in last years as an emerging health threat2. However, these new studies have pointed to neurotropic properties of the virus that could be used in a beneficial way against the unfavorable prognosis gliomas. There are still many safety measures to be taken, such as making a genetically stable virus with attenuated replication in differentiated neural cells, but ongoing research is already having good results3.

Referências


References 1Castañeda C.A., et al. Glioblastoma: Análisis Molecular Y Sus Implicancias Clínicas. Rev Peru Med Exp Salud Publica. 2015; 32(2):316-25.

, 05, 06 and 07 October 2017 – Dourados – MS - Brasil

Sais J.C., et al. Zika Virus: What Have We Learnt Since the Start of the Recent Epidemic? Front Microbiol. 2017; 8: 1554. doi: 10.3389/fmicb.2017.01554. 3Zhu Z., et al. Zika virus has oncolytic activity against glioblastoma stem cells. J. Exp. Med. 2017. http://dx.doi.org/10.1084/jem.20171093. 4Southam C.M., Moore A.E. Clinical studies of viruses as antineoplastic agents with particular reference to Egypt 101 virus. Cancer. 5:1025–1034. 1952. http ://dx .doi .org /10 .1002 /1097 -0142(195209)5 :5<1025::AID-CNCR2820050518>3.0.CO;2-Q


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