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Modeling mosquito-borne and sexual transmission of Zika virus in an enzootic host, the African green monkey
Mosquito-borne and sexual transmission of Zika virus (ZIKV), a TORCH pathogen, recently initiated a series of large epidemics throughout the Tropics. Animal models are necessary to determine transmission risk and study pathogenesis, as well screen antivirals and vaccine candidates. In this study, we...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343349/ https://www.ncbi.nlm.nih.gov/pubmed/32569276 http://dx.doi.org/10.1371/journal.pntd.0008107 |
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author | Haddow, Andrew D. Perez-Sautu, Unai Wiley, Michael R. Miller, Lynn J. Kimmel, Adrienne E. Principe, Lucia M. Wollen-Roberts, Suzanne E. Shamblin, Joshua D. Valdez, Stephanie M. Cazares, Lisa H. Pratt, William D. Rossi, Franco D. Lugo-Roman, Luis Bavari, Sina Palacios, Gustavo F. Nalca, Aysegul Nasar, Farooq Pitt, M. Louise M. |
author_facet | Haddow, Andrew D. Perez-Sautu, Unai Wiley, Michael R. Miller, Lynn J. Kimmel, Adrienne E. Principe, Lucia M. Wollen-Roberts, Suzanne E. Shamblin, Joshua D. Valdez, Stephanie M. Cazares, Lisa H. Pratt, William D. Rossi, Franco D. Lugo-Roman, Luis Bavari, Sina Palacios, Gustavo F. Nalca, Aysegul Nasar, Farooq Pitt, M. Louise M. |
author_sort | Haddow, Andrew D. |
collection | PubMed |
description | Mosquito-borne and sexual transmission of Zika virus (ZIKV), a TORCH pathogen, recently initiated a series of large epidemics throughout the Tropics. Animal models are necessary to determine transmission risk and study pathogenesis, as well screen antivirals and vaccine candidates. In this study, we modeled mosquito and sexual transmission of ZIKV in the African green monkey (AGM). Following subcutaneous, intravaginal or intrarectal inoculation of AGMs with ZIKV, we determined the transmission potential and infection dynamics of the virus. AGMs inoculated by all three transmission routes exhibited viremia and viral shedding followed by strong virus neutralizing antibody responses, in the absence of clinical illness. All four of the subcutaneously inoculated AGMs became infected (mean peak viremia: 2.9 log(10) PFU/mL, mean duration: 4.3 days) and vRNA was detected in their oral swabs, with infectious virus being detected in a subset of these specimens. Although all four of the intravaginally inoculated AGMs developed virus neutralizing antibody responses, only three had detectable viremia (mean peak viremia: 4.0 log(10) PFU/mL, mean duration: 3.0 days). These three AGMs also had vRNA and infectious virus detected in both oral and vaginal swabs. Two of the four intrarectally inoculated AGMs became infected (mean peak viremia: 3.8 log(10) PFU/mL, mean duration: 3.5 days). vRNA was detected in oral swabs collected from both of these infected AGMs, and infectious virus was detected in an oral swab from one of these AGMs. Notably, vRNA and infectious virus were detected in vaginal swabs collected from the infected female AGM (peak viral load: 7.5 log(10) copies/mL, peak titer: 3.8 log(10) PFU/mL, range of detection: 5–21 days post infection). Abnormal clinical chemistry and hematology results were detected and acute lymphadenopathy was observed in some AGMs. Infection dynamics in all three AGM ZIKV models are similar to those reported in the majority of human ZIKV infections. Our results indicate that the AGM can be used as a surrogate to model mosquito or sexual ZIKV transmission and infection. Furthermore, our results suggest that AGMs are likely involved in the enzootic maintenance and amplification cycle of ZIKV. |
format | Online Article Text |
id | pubmed-7343349 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-73433492020-07-17 Modeling mosquito-borne and sexual transmission of Zika virus in an enzootic host, the African green monkey Haddow, Andrew D. Perez-Sautu, Unai Wiley, Michael R. Miller, Lynn J. Kimmel, Adrienne E. Principe, Lucia M. Wollen-Roberts, Suzanne E. Shamblin, Joshua D. Valdez, Stephanie M. Cazares, Lisa H. Pratt, William D. Rossi, Franco D. Lugo-Roman, Luis Bavari, Sina Palacios, Gustavo F. Nalca, Aysegul Nasar, Farooq Pitt, M. Louise M. PLoS Negl Trop Dis Research Article Mosquito-borne and sexual transmission of Zika virus (ZIKV), a TORCH pathogen, recently initiated a series of large epidemics throughout the Tropics. Animal models are necessary to determine transmission risk and study pathogenesis, as well screen antivirals and vaccine candidates. In this study, we modeled mosquito and sexual transmission of ZIKV in the African green monkey (AGM). Following subcutaneous, intravaginal or intrarectal inoculation of AGMs with ZIKV, we determined the transmission potential and infection dynamics of the virus. AGMs inoculated by all three transmission routes exhibited viremia and viral shedding followed by strong virus neutralizing antibody responses, in the absence of clinical illness. All four of the subcutaneously inoculated AGMs became infected (mean peak viremia: 2.9 log(10) PFU/mL, mean duration: 4.3 days) and vRNA was detected in their oral swabs, with infectious virus being detected in a subset of these specimens. Although all four of the intravaginally inoculated AGMs developed virus neutralizing antibody responses, only three had detectable viremia (mean peak viremia: 4.0 log(10) PFU/mL, mean duration: 3.0 days). These three AGMs also had vRNA and infectious virus detected in both oral and vaginal swabs. Two of the four intrarectally inoculated AGMs became infected (mean peak viremia: 3.8 log(10) PFU/mL, mean duration: 3.5 days). vRNA was detected in oral swabs collected from both of these infected AGMs, and infectious virus was detected in an oral swab from one of these AGMs. Notably, vRNA and infectious virus were detected in vaginal swabs collected from the infected female AGM (peak viral load: 7.5 log(10) copies/mL, peak titer: 3.8 log(10) PFU/mL, range of detection: 5–21 days post infection). Abnormal clinical chemistry and hematology results were detected and acute lymphadenopathy was observed in some AGMs. Infection dynamics in all three AGM ZIKV models are similar to those reported in the majority of human ZIKV infections. Our results indicate that the AGM can be used as a surrogate to model mosquito or sexual ZIKV transmission and infection. Furthermore, our results suggest that AGMs are likely involved in the enzootic maintenance and amplification cycle of ZIKV. Public Library of Science 2020-06-22 /pmc/articles/PMC7343349/ /pubmed/32569276 http://dx.doi.org/10.1371/journal.pntd.0008107 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
spellingShingle | Research Article Haddow, Andrew D. Perez-Sautu, Unai Wiley, Michael R. Miller, Lynn J. Kimmel, Adrienne E. Principe, Lucia M. Wollen-Roberts, Suzanne E. Shamblin, Joshua D. Valdez, Stephanie M. Cazares, Lisa H. Pratt, William D. Rossi, Franco D. Lugo-Roman, Luis Bavari, Sina Palacios, Gustavo F. Nalca, Aysegul Nasar, Farooq Pitt, M. Louise M. Modeling mosquito-borne and sexual transmission of Zika virus in an enzootic host, the African green monkey |
title | Modeling mosquito-borne and sexual transmission of Zika virus in an enzootic host, the African green monkey |
title_full | Modeling mosquito-borne and sexual transmission of Zika virus in an enzootic host, the African green monkey |
title_fullStr | Modeling mosquito-borne and sexual transmission of Zika virus in an enzootic host, the African green monkey |
title_full_unstemmed | Modeling mosquito-borne and sexual transmission of Zika virus in an enzootic host, the African green monkey |
title_short | Modeling mosquito-borne and sexual transmission of Zika virus in an enzootic host, the African green monkey |
title_sort | modeling mosquito-borne and sexual transmission of zika virus in an enzootic host, the african green monkey |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343349/ https://www.ncbi.nlm.nih.gov/pubmed/32569276 http://dx.doi.org/10.1371/journal.pntd.0008107 |
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