Host Molecules Regulating Neural Invasion of Zika Virus and Drug Repurposing Strategy
Zika virus (ZIKV) is a mosquito-borne, single-stranded RNA virus belonging to the genus Flavivirus. Although ZIKV infection is usually known to exhibit mild clinical symptoms, intrauterine ZIKV infections have been associated with severe neurological manifestations, including microcephaly and Guilla...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.743147/full |
| _version_ | 1818910130620596224 |
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| author | Li Yin Tan Li Yin Tan Thamil Vaani Komarasamy William James Vinod R. M. T. Balasubramaniam |
| author_facet | Li Yin Tan Li Yin Tan Thamil Vaani Komarasamy William James Vinod R. M. T. Balasubramaniam |
| author_sort | Li Yin Tan |
| collection | DOAJ |
| description | Zika virus (ZIKV) is a mosquito-borne, single-stranded RNA virus belonging to the genus Flavivirus. Although ZIKV infection is usually known to exhibit mild clinical symptoms, intrauterine ZIKV infections have been associated with severe neurological manifestations, including microcephaly and Guillain Barre syndrome (GBS). Therefore, it is imperative to understand the mechanisms of ZIKV entry into the central nervous system (CNS) and its effect on brain cells. Several routes of neuro-invasion have been identified, among which blood–brain barrier (BBB) disruption is the commonest mode of access. The molecular receptors involved in viral entry remain unknown; with various proposed molecular ZIKV-host interactions including potential non-receptor mediated cellular entry. As ZIKV invade neuronal cells, they trigger neurotoxic mechanisms via cell-autonomous and non-cell autonomous pathways, resulting in neurogenesis dysfunction, viral replication, and cell death, all of which eventually lead to microcephaly. Together, our understanding of the biological mechanisms of ZIKV exposure would aid in the development of anti-ZIKV therapies targeting host cellular and/or viral components to combat ZIKV infection and its neurological manifestations. In this present work, we review the current understanding of ZIKV entry mechanisms into the CNS and its implications on the brain. We also highlight the status of the drug repurposing approach for the development of potential antiviral drugs against ZIKV. |
| first_indexed | 2024-12-19T22:37:55Z |
| format | Article |
| id | doaj.art-aad3235266b849f6b06593d25386362d |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-19T22:37:55Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-aad3235266b849f6b06593d25386362d2022-12-21T20:03:08ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-03-011310.3389/fmicb.2022.743147743147Host Molecules Regulating Neural Invasion of Zika Virus and Drug Repurposing StrategyLi Yin Tan0Li Yin Tan1Thamil Vaani Komarasamy2William James3Vinod R. M. T. Balasubramaniam4Infection and Immunity Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, MalaysiaGreenslopes Private Hospital, Greenslopes, QLD, AustraliaInfection and Immunity Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, MalaysiaSir William Dunn School of Pathology, University of Oxford, Oxford, United KingdomInfection and Immunity Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, MalaysiaZika virus (ZIKV) is a mosquito-borne, single-stranded RNA virus belonging to the genus Flavivirus. Although ZIKV infection is usually known to exhibit mild clinical symptoms, intrauterine ZIKV infections have been associated with severe neurological manifestations, including microcephaly and Guillain Barre syndrome (GBS). Therefore, it is imperative to understand the mechanisms of ZIKV entry into the central nervous system (CNS) and its effect on brain cells. Several routes of neuro-invasion have been identified, among which blood–brain barrier (BBB) disruption is the commonest mode of access. The molecular receptors involved in viral entry remain unknown; with various proposed molecular ZIKV-host interactions including potential non-receptor mediated cellular entry. As ZIKV invade neuronal cells, they trigger neurotoxic mechanisms via cell-autonomous and non-cell autonomous pathways, resulting in neurogenesis dysfunction, viral replication, and cell death, all of which eventually lead to microcephaly. Together, our understanding of the biological mechanisms of ZIKV exposure would aid in the development of anti-ZIKV therapies targeting host cellular and/or viral components to combat ZIKV infection and its neurological manifestations. In this present work, we review the current understanding of ZIKV entry mechanisms into the CNS and its implications on the brain. We also highlight the status of the drug repurposing approach for the development of potential antiviral drugs against ZIKV.https://www.frontiersin.org/articles/10.3389/fmicb.2022.743147/fullzika virusblood-brain barriertranscytosisTrojan horseinflammatory responseendoplasmic reticulum stress |
| spellingShingle | Li Yin Tan Li Yin Tan Thamil Vaani Komarasamy William James Vinod R. M. T. Balasubramaniam Host Molecules Regulating Neural Invasion of Zika Virus and Drug Repurposing Strategy Frontiers in Microbiology zika virus blood-brain barrier transcytosis Trojan horse inflammatory response endoplasmic reticulum stress |
| title | Host Molecules Regulating Neural Invasion of Zika Virus and Drug Repurposing Strategy |
| title_full | Host Molecules Regulating Neural Invasion of Zika Virus and Drug Repurposing Strategy |
| title_fullStr | Host Molecules Regulating Neural Invasion of Zika Virus and Drug Repurposing Strategy |
| title_full_unstemmed | Host Molecules Regulating Neural Invasion of Zika Virus and Drug Repurposing Strategy |
| title_short | Host Molecules Regulating Neural Invasion of Zika Virus and Drug Repurposing Strategy |
| title_sort | host molecules regulating neural invasion of zika virus and drug repurposing strategy |
| topic | zika virus blood-brain barrier transcytosis Trojan horse inflammatory response endoplasmic reticulum stress |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.743147/full |
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