Simian Immunodeficiency Virus Infection of Rhesus Macaques Results in Delayed Zika Virus Clearance
ABSTRACT Flaviviruses are controlled by adaptive immune responses but are exquisitely sensitive to interferon-stimulated genes (ISGs). How coinfections, particularly simian immunodeficiency viruses (SIVs), that induce robust ISG signatures influence flavivirus clearance and pathogenesis is unclear....
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2019-12-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.02790-19 |
| _version_ | 1818995570683936768 |
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| author | Carol L. Vinton Samuel J. Magaziner Kimberly A. Dowd Shelly J. Robertson Emerito Amaro-Carambot Erik P. Karmele Alexandra M. Ortiz Carly E. Starke Joseph C. Mudd Stephen S. Whitehead Sonja M. Best Theodore C. Pierson Heather D. Hickman Jason M. Brenchley |
| author_facet | Carol L. Vinton Samuel J. Magaziner Kimberly A. Dowd Shelly J. Robertson Emerito Amaro-Carambot Erik P. Karmele Alexandra M. Ortiz Carly E. Starke Joseph C. Mudd Stephen S. Whitehead Sonja M. Best Theodore C. Pierson Heather D. Hickman Jason M. Brenchley |
| author_sort | Carol L. Vinton |
| collection | DOAJ |
| description | ABSTRACT Flaviviruses are controlled by adaptive immune responses but are exquisitely sensitive to interferon-stimulated genes (ISGs). How coinfections, particularly simian immunodeficiency viruses (SIVs), that induce robust ISG signatures influence flavivirus clearance and pathogenesis is unclear. Here, we studied how Zika virus (ZIKV) infection is modulated in SIV-infected nonhuman primates. We measured ZIKV replication, cellular ZIKV RNA levels, and immune responses in non-SIV-infected and SIV-infected rhesus macaques (RMs), which we infected with ZIKV. Coinfected animals had a 1- to 2-day delay in peak ZIKV viremia, which was 30% of that in non-SIV-infected animals. However, ZIKV viremia was significantly prolonged in SIV-positive (SIV+) RMs. ISG levels at the time of ZIKV infection were predictive for lower ZIKV viremia in the SIV+ RMs, while prolonged ZIKV viremia was associated with muted and delayed adaptive responses in SIV+ RMs. IMPORTANCE Immunocompromised individuals often become symptomatic with infections which are normally fairly asymptomatic in healthy individuals. The particular mechanisms that underlie susceptibility to coinfections in human immunodeficiency virus (HIV)-infected individuals are multifaceted. ZIKV and other flaviviruses are sensitive to neutralizing antibodies, whose production can be limited in HIV-infected individuals but are also sensitive to type I interferons, which are expressed at high levels in HIV-infected individuals. Data in this study highlight how individual components of the innate and adaptive immune responses which become perturbed in HIV-infected individuals influence ZIKV infection. |
| first_indexed | 2024-12-20T21:15:57Z |
| format | Article |
| id | doaj.art-38d4fedb46b448498b0af972c8906ef0 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-20T21:15:57Z |
| publishDate | 2019-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-38d4fedb46b448498b0af972c8906ef02022-12-21T19:26:26ZengAmerican Society for MicrobiologymBio2150-75112019-12-0110610.1128/mBio.02790-19Simian Immunodeficiency Virus Infection of Rhesus Macaques Results in Delayed Zika Virus ClearanceCarol L. Vinton0Samuel J. Magaziner1Kimberly A. Dowd2Shelly J. Robertson3Emerito Amaro-Carambot4Erik P. Karmele5Alexandra M. Ortiz6Carly E. Starke7Joseph C. Mudd8Stephen S. Whitehead9Sonja M. Best10Theodore C. Pierson11Heather D. Hickman12Jason M. Brenchley13Barrier Immunity Section, Laboratory of Viral Diseases, NIAID/NIH, Bethesda, Maryland, USAViral Immunity and Pathogenesis Unit, Laboratory of Clinical Immunology & Microbiology, NIAID/NIH, Bethesda, Maryland, USAViral Pathogenesis Section, Laboratory of Viral Diseases, NIAID/NIH, Bethesda, Maryland, USAInnate Immunity & Pathogenesis Section, Laboratory of Virology, NIAID/NIH, Hamilton, Montana, USAViral Pathogenesis Section, Laboratory of Viral Diseases, NIAID/NIH, Bethesda, Maryland, USAMucosal Immunobiology Section, Laboratory of Molecular Immunology, NIAID/NIH, Bethesda, Maryland, USABarrier Immunity Section, Laboratory of Viral Diseases, NIAID/NIH, Bethesda, Maryland, USABarrier Immunity Section, Laboratory of Viral Diseases, NIAID/NIH, Bethesda, Maryland, USABarrier Immunity Section, Laboratory of Viral Diseases, NIAID/NIH, Bethesda, Maryland, USAViral Pathogenesis Section, Laboratory of Viral Diseases, NIAID/NIH, Bethesda, Maryland, USAInnate Immunity & Pathogenesis Section, Laboratory of Virology, NIAID/NIH, Hamilton, Montana, USAViral Pathogenesis Section, Laboratory of Viral Diseases, NIAID/NIH, Bethesda, Maryland, USAViral Immunity and Pathogenesis Unit, Laboratory of Clinical Immunology & Microbiology, NIAID/NIH, Bethesda, Maryland, USABarrier Immunity Section, Laboratory of Viral Diseases, NIAID/NIH, Bethesda, Maryland, USAABSTRACT Flaviviruses are controlled by adaptive immune responses but are exquisitely sensitive to interferon-stimulated genes (ISGs). How coinfections, particularly simian immunodeficiency viruses (SIVs), that induce robust ISG signatures influence flavivirus clearance and pathogenesis is unclear. Here, we studied how Zika virus (ZIKV) infection is modulated in SIV-infected nonhuman primates. We measured ZIKV replication, cellular ZIKV RNA levels, and immune responses in non-SIV-infected and SIV-infected rhesus macaques (RMs), which we infected with ZIKV. Coinfected animals had a 1- to 2-day delay in peak ZIKV viremia, which was 30% of that in non-SIV-infected animals. However, ZIKV viremia was significantly prolonged in SIV-positive (SIV+) RMs. ISG levels at the time of ZIKV infection were predictive for lower ZIKV viremia in the SIV+ RMs, while prolonged ZIKV viremia was associated with muted and delayed adaptive responses in SIV+ RMs. IMPORTANCE Immunocompromised individuals often become symptomatic with infections which are normally fairly asymptomatic in healthy individuals. The particular mechanisms that underlie susceptibility to coinfections in human immunodeficiency virus (HIV)-infected individuals are multifaceted. ZIKV and other flaviviruses are sensitive to neutralizing antibodies, whose production can be limited in HIV-infected individuals but are also sensitive to type I interferons, which are expressed at high levels in HIV-infected individuals. Data in this study highlight how individual components of the innate and adaptive immune responses which become perturbed in HIV-infected individuals influence ZIKV infection.https://journals.asm.org/doi/10.1128/mBio.02790-19SIVZIKVinnate immunitytype I interferon |
| spellingShingle | Carol L. Vinton Samuel J. Magaziner Kimberly A. Dowd Shelly J. Robertson Emerito Amaro-Carambot Erik P. Karmele Alexandra M. Ortiz Carly E. Starke Joseph C. Mudd Stephen S. Whitehead Sonja M. Best Theodore C. Pierson Heather D. Hickman Jason M. Brenchley Simian Immunodeficiency Virus Infection of Rhesus Macaques Results in Delayed Zika Virus Clearance mBio SIV ZIKV innate immunity type I interferon |
| title | Simian Immunodeficiency Virus Infection of Rhesus Macaques Results in Delayed Zika Virus Clearance |
| title_full | Simian Immunodeficiency Virus Infection of Rhesus Macaques Results in Delayed Zika Virus Clearance |
| title_fullStr | Simian Immunodeficiency Virus Infection of Rhesus Macaques Results in Delayed Zika Virus Clearance |
| title_full_unstemmed | Simian Immunodeficiency Virus Infection of Rhesus Macaques Results in Delayed Zika Virus Clearance |
| title_short | Simian Immunodeficiency Virus Infection of Rhesus Macaques Results in Delayed Zika Virus Clearance |
| title_sort | simian immunodeficiency virus infection of rhesus macaques results in delayed zika virus clearance |
| topic | SIV ZIKV innate immunity type I interferon |
| url | https://journals.asm.org/doi/10.1128/mBio.02790-19 |
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