Neurocognitive impact of Zika virus infection in adult rhesus macaques
Abstract Background Zika virus (ZIKV) is a mosquito-transmitted flavivirus that affects many regions of the world. Infection, in utero, causes microcephaly and later developmental and neurologic impairments. The impact of ZIKV infection on neurocognition in adults has not been well described. The ob...
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| Format: | Article |
| Language: | English |
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BMC
2022-02-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-022-02402-4 |
| _version_ | 1818977241056411648 |
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| author | Denise C. Hsu Kesara Chumpolkulwong Michael J. Corley Taweewun Hunsawong Dutsadee Inthawong Alexandra Schuetz Rawiwan Imerbsin Decha Silsorn Panupat Nadee Jumpol Sopanaporn Yuwadee Phuang-Ngern Chonticha Klungthong Matthew Reed Stefan Fernandez Lishomwa C. Ndhlovu Robert Paul Luis Lugo-Roman Nelson L. Michael Kayvon Modjarrad Sandhya Vasan |
| author_facet | Denise C. Hsu Kesara Chumpolkulwong Michael J. Corley Taweewun Hunsawong Dutsadee Inthawong Alexandra Schuetz Rawiwan Imerbsin Decha Silsorn Panupat Nadee Jumpol Sopanaporn Yuwadee Phuang-Ngern Chonticha Klungthong Matthew Reed Stefan Fernandez Lishomwa C. Ndhlovu Robert Paul Luis Lugo-Roman Nelson L. Michael Kayvon Modjarrad Sandhya Vasan |
| author_sort | Denise C. Hsu |
| collection | DOAJ |
| description | Abstract Background Zika virus (ZIKV) is a mosquito-transmitted flavivirus that affects many regions of the world. Infection, in utero, causes microcephaly and later developmental and neurologic impairments. The impact of ZIKV infection on neurocognition in adults has not been well described. The objective of the study was to assess the neurocognitive impact of ZIKV infection in adult rhesus macaques. Methods Neurocognitive assessments were performed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) via a touch screen and modified Brinkman Board before and after subcutaneous ZIKV inoculation. Immune activation markers were measured in the blood and cerebral spinal fluid (CSF) by multiplex assay and flow cytometry. Results All animals (N = 8) had detectable ZIKV RNA in plasma at day 1 post-inoculation (PI) that peaked at day 2 PI (median 5.9, IQR 5.6–6.2 log10 genome equivalents/mL). In all eight animals, ZIKV RNA became undetectable in plasma by day 14 PI, but persisted in lymphoid tissues. ZIKV RNA was not detected in the CSF supernatant at days 4, 8, 14 and 28 PI but was detected in the brain of 2 animals at days 8 and 28 PI. Elevations in markers of immune activation in the blood and CSF were accompanied by a reduction in accuracy and reaction speed on the CANTAB in the majority of animals. Conclusions The co-occurrence of systemic and CSF immune perturbations and neurocognitive impairment establishes this model as useful for studying the impact of neuroinflammation on neurobehavior in rhesus macaques, as it pertains to ZIKV infection and potentially other pathogens. |
| first_indexed | 2024-12-20T16:24:36Z |
| format | Article |
| id | doaj.art-e9647a938c85447f9d074e858696630c |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-20T16:24:36Z |
| publishDate | 2022-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-e9647a938c85447f9d074e858696630c2022-12-21T19:33:30ZengBMCJournal of Neuroinflammation1742-20942022-02-0119111310.1186/s12974-022-02402-4Neurocognitive impact of Zika virus infection in adult rhesus macaquesDenise C. Hsu0Kesara Chumpolkulwong1Michael J. Corley2Taweewun Hunsawong3Dutsadee Inthawong4Alexandra Schuetz5Rawiwan Imerbsin6Decha Silsorn7Panupat Nadee8Jumpol Sopanaporn9Yuwadee Phuang-Ngern10Chonticha Klungthong11Matthew Reed12Stefan Fernandez13Lishomwa C. Ndhlovu14Robert Paul15Luis Lugo-Roman16Nelson L. Michael17Kayvon Modjarrad18Sandhya Vasan19US Military HIV Research Program, Walter Reed Army Institute of ResearchArmed Forces Research Institute of Medical SciencesDivision of Infectious Diseases, Department of Medicine, Weill Cornell MedicineArmed Forces Research Institute of Medical SciencesArmed Forces Research Institute of Medical SciencesUS Military HIV Research Program, Walter Reed Army Institute of ResearchArmed Forces Research Institute of Medical SciencesArmed Forces Research Institute of Medical SciencesArmed Forces Research Institute of Medical SciencesArmed Forces Research Institute of Medical SciencesArmed Forces Research Institute of Medical SciencesArmed Forces Research Institute of Medical SciencesArmed Forces Research Institute of Medical SciencesArmed Forces Research Institute of Medical SciencesDivision of Infectious Diseases, Department of Medicine, Weill Cornell MedicineMissouri Institute of Mental Health, University of MissouriArmed Forces Research Institute of Medical SciencesCenter for Infectious Diseases Research, Walter Reed Army Institute of ResearchEmerging Infectious Disease Branch, Walter Reed Army Institute of ResearchUS Military HIV Research Program, Walter Reed Army Institute of ResearchAbstract Background Zika virus (ZIKV) is a mosquito-transmitted flavivirus that affects many regions of the world. Infection, in utero, causes microcephaly and later developmental and neurologic impairments. The impact of ZIKV infection on neurocognition in adults has not been well described. The objective of the study was to assess the neurocognitive impact of ZIKV infection in adult rhesus macaques. Methods Neurocognitive assessments were performed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) via a touch screen and modified Brinkman Board before and after subcutaneous ZIKV inoculation. Immune activation markers were measured in the blood and cerebral spinal fluid (CSF) by multiplex assay and flow cytometry. Results All animals (N = 8) had detectable ZIKV RNA in plasma at day 1 post-inoculation (PI) that peaked at day 2 PI (median 5.9, IQR 5.6–6.2 log10 genome equivalents/mL). In all eight animals, ZIKV RNA became undetectable in plasma by day 14 PI, but persisted in lymphoid tissues. ZIKV RNA was not detected in the CSF supernatant at days 4, 8, 14 and 28 PI but was detected in the brain of 2 animals at days 8 and 28 PI. Elevations in markers of immune activation in the blood and CSF were accompanied by a reduction in accuracy and reaction speed on the CANTAB in the majority of animals. Conclusions The co-occurrence of systemic and CSF immune perturbations and neurocognitive impairment establishes this model as useful for studying the impact of neuroinflammation on neurobehavior in rhesus macaques, as it pertains to ZIKV infection and potentially other pathogens.https://doi.org/10.1186/s12974-022-02402-4Zika virusNeurocognitionNeurobehaviorNeuro-inflammation |
| spellingShingle | Denise C. Hsu Kesara Chumpolkulwong Michael J. Corley Taweewun Hunsawong Dutsadee Inthawong Alexandra Schuetz Rawiwan Imerbsin Decha Silsorn Panupat Nadee Jumpol Sopanaporn Yuwadee Phuang-Ngern Chonticha Klungthong Matthew Reed Stefan Fernandez Lishomwa C. Ndhlovu Robert Paul Luis Lugo-Roman Nelson L. Michael Kayvon Modjarrad Sandhya Vasan Neurocognitive impact of Zika virus infection in adult rhesus macaques Journal of Neuroinflammation Zika virus Neurocognition Neurobehavior Neuro-inflammation |
| title | Neurocognitive impact of Zika virus infection in adult rhesus macaques |
| title_full | Neurocognitive impact of Zika virus infection in adult rhesus macaques |
| title_fullStr | Neurocognitive impact of Zika virus infection in adult rhesus macaques |
| title_full_unstemmed | Neurocognitive impact of Zika virus infection in adult rhesus macaques |
| title_short | Neurocognitive impact of Zika virus infection in adult rhesus macaques |
| title_sort | neurocognitive impact of zika virus infection in adult rhesus macaques |
| topic | Zika virus Neurocognition Neurobehavior Neuro-inflammation |
| url | https://doi.org/10.1186/s12974-022-02402-4 |
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