Zika Virus Tissue and Blood Compartmentalization in Acute Infection of Rhesus Macaques.

Lark L Coffey,Eric Delwart,Jennifer Watanabe,Rebekah I Keesler,Anne M Gibbons,Anil Singapuri,Patricia A Pesavento,Mars Stone,Kui Gao,Sonia Bakkour,Koen K A Van Rompay,Graham Simmons,Christina Cruzen,Jeff Linnen,Rie Watanabe,Wilhelm Von Morgenland,J Rachel Reader,Michael P Busch ,John H Morrison ,Eliza Bliss‐Moreau ,Marion C Lanteri ,Kari L Christe ,Yee Jurng-Jae ,Ashley Allen

doi:10.1371/journal.pone.0171148

Abstract

Animal models of Zika virus (ZIKV) are needed to better understand tropism and pathogenesis and to test candidate vaccines and therapies to curtail the pandemic. Humans and rhesus macaques possess similar fetal development and placental biology that is not shared between humans and rodents. We inoculated 2 non-pregnant rhesus macaques with a 2015 Brazilian ZIKV strain. Consistent with most human infections, the animals experienced no clinical disease but developed short-lived plasma viremias that cleared as neutralizing antibody developed. In 1 animal, viral RNA (vRNA) could be detected longer in whole blood than in plasma. Despite no major histopathologic changes, many adult tissues contained vRNA 14 days post-infection with highest levels in hemolymphatic tissues. These observations warrant further studies to investigate ZIKV persistence and its potential clinical implications for transmission via blood products or tissue and organ transplants.

Highlights

Emerging mosquito-borne Zika virus (ZIKV, Flaviviridae, flavivirus) was first detected in Brazil in 2015 and has since spread to at least 60 countries in South and Central America, Oceania and Asia [1]
Complete blood counts and lymphocyte phenotyping data from sampling days showed minor changes such as a transient decrease of platelets and B lymphocytes during the first week of infection, and at approximately 1 week, a transient decrease of neutrophils and increase of monocytes and lymphocytes; these changes may be due to ZIKV infection as observed in humans and/or the frequent sedation schedule
Viremias peaked at 2.2 or 2.5 log10 plaque-forming units (PFU)/ml 2 dpi and were not detectable after 4 dpi (Fig 1B and 1C). These results show that rhesus macaques intravenously inoculated with 5.0 log10 PFU of a 2015 Brazilian strain of ZIKV become infected and clear plasma of detectable infectious virus by 4 dpi, plasma of viral RNA (vRNA) by 8 dpi, and whole blood of vRNA by 12 dpi

Summary

Introduction

Emerging mosquito-borne Zika virus (ZIKV, Flaviviridae, flavivirus) was first detected in Brazil in 2015 and has since spread to at least 60 countries in South and Central America, Oceania and Asia [1]. An additional 35,000 cases were reported in US Territories. Local mosquito-borne transmission in Florida was first documented in July 2016 with 210 local cases reported as of December 28, 2016 [2]. The World Health Organization declared the ongoing ZIKV outbreaks a public health emergency on February 1, 2016 [7] based on explosive geographic spread, clinical and epidemiological associations with microcephaly [8,9,10,11] and other neurological defects (reviewed in [12]), and lack of a licensed vaccine or PLOS ONE | DOI:10.1371/journal.pone.0171148. The World Health Organization declared the ongoing ZIKV outbreaks a public health emergency on February 1, 2016 [7] based on explosive geographic spread, clinical and epidemiological associations with microcephaly [8,9,10,11] and other neurological defects (reviewed in [12]), and lack of a licensed vaccine or PLOS ONE | DOI:10.1371/journal.pone.0171148 January 31, 2017

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