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....

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	SIV ZIKV innate immunity type I interferon Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/38d4fedb46b448498b0af972c8906ef0
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spelling	oai:doaj.org-article:38d4fedb46b448498b0af972c8906ef02021-11-15T15:54:47ZSimian Immunodeficiency Virus Infection of Rhesus Macaques Results in Delayed Zika Virus Clearance10.1128/mBio.02790-192150-7511https://doaj.org/article/38d4fedb46b448498b0af972c8906ef02019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02790-19https://doaj.org/toc/2150-7511ABSTRACT 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.Carol L. VintonSamuel J. MagazinerKimberly A. DowdShelly J. RobertsonEmerito Amaro-CarambotErik P. KarmeleAlexandra M. OrtizCarly E. StarkeJoseph C. MuddStephen S. WhiteheadSonja M. BestTheodore C. PiersonHeather D. HickmanJason M. BrenchleyAmerican Society for MicrobiologyarticleSIVZIKVinnate immunitytype I interferonMicrobiologyQR1-502ENmBio, Vol 10, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	SIV ZIKV innate immunity type I interferon Microbiology QR1-502
spellingShingle	SIV ZIKV innate immunity type I interferon Microbiology QR1-502 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
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.
format	article
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
title	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_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_sort	simian immunodeficiency virus infection of rhesus macaques results in delayed zika virus clearance
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/38d4fedb46b448498b0af972c8906ef0
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Simian Immunodeficiency Virus Infection of Rhesus Macaques Results in Delayed Zika Virus Clearance

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