Zika Virus infection of rhesus macaques leads to viral persistence in multiple tissues.

Patricia P Smith,Victor R Defilippis,Michael Denton,Rebecca Ducore ,Rebecca Broeckel ,Michael K Axthelm,Tonya Swanson,Craig N Kreklywich ,Nicole Haese ,Daniel N Streblow,Jessica L Smith,Alfred W Legasse,Christopher J Parkins,Jay A Nelson,Clayton A Wiley,William B Messer,Rhonda Macallister,Alec J Hirsch,Peta L Grigsby,Jon D Hennebold,Lois M.a Colgin

doi:10.1371/journal.ppat.1006219

Abstract

Zika virus (ZIKV), an emerging flavivirus, has recently spread explosively through the Western hemisphere. In addition to symptoms including fever, rash, arthralgia, and conjunctivitis, ZIKV infection of pregnant women can cause microcephaly and other developmental abnormalities in the fetus. We report herein the results of ZIKV infection of adult rhesus macaques. Following subcutaneous infection, animals developed transient plasma viremia and viruria from 1–7 days post infection (dpi) that was accompanied by the development of a rash, fever and conjunctivitis. Animals produced a robust adaptive immune response to ZIKV, although systemic cytokine response was minimal. At 7 dpi, virus was detected in peripheral nervous tissue, multiple lymphoid tissues, joints, and the uterus of the necropsied animals. Notably, viral RNA persisted in neuronal, lymphoid and joint/muscle tissues and the male and female reproductive tissues through 28 to 35 dpi. The tropism and persistence of ZIKV in the peripheral nerves and reproductive tract may provide a mechanism of subsequent neuropathogenesis and sexual transmission.

Highlights

Zika virus (ZIKV), once a little-studied member of the family Flaviviridae, forcefully emerged across the Western Hemisphere in 2015–16
Reported instances of human ZIKV-associated disease during the 20th century had been sporadic with generally mild disease, large outbreaks were reported in Yap State, Micronesia in 2007 and in French Polynesia in 2013, resulting in ~900 and 30,000 symptomatic cases, respectively [6,7]
The third cohort, consisting of two adult male rhesus macaque (RM), was infected with 1x105 ffu followed by daily sampling of blood and urine through 35 dpi

Summary

Introduction

Zika virus (ZIKV), once a little-studied member of the family Flaviviridae, forcefully emerged across the Western Hemisphere in 2015–16. Reported instances of human ZIKV-associated disease during the 20th century had been sporadic with generally mild disease, large outbreaks were reported in Yap State, Micronesia in 2007 and in French Polynesia in 2013, resulting in ~900 and 30,000 symptomatic cases, respectively [6,7]. Illness during these outbreaks was initially characterized as self-limiting and did not require hospitalization. 74 patients in French Polynesia who experienced confirmed or probable ZIKV infection later presented with neurological complications Over half of these were characterized as Guillain-Barresyndrome (GBS); the remainder included various encephalitides, paraesthesia, facial paralysis and myelitis. Differences in placental architecture and fetal development in the mouse vis-à-vis humans suggest that certain aspects of ZIKV pathogenesis during pregnancy may not be reflected in the murine infection model [15]

Methods

Results

Conclusion