ZIKV Demonstrates Minimal Pathologic Effects and Mosquito Infectivity in Viremic Cynomolgus Macaques

Sasha Azar,Shannan Rossi,Nikos Vasilakis,Jing Huang,Juan Olano,Jiehua Zhou,Scott Weaver,Ruimei Yun,Kathryn Hanley,Jessica Plante,Christopher Roundy,Sherry Haller

doi:10.3390/v10110661

Sasha Azar, Shannan Rossi + Show 10 more

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https://doi.org/10.3390/v10110661

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Abstract

To evaluate the effects of ZIKV infection on non-human primates (NHPs), as well as to investigate whether these NHPs develop sufficient viremia to infect the major urban vector mosquito, Aedes aegypti, four cynomolgus macaques (Macaca fascicularis) were subcutaneously infected with 5.0 log10 focus-forming units (FFU) of DNA clone-derived ZIKV strain FSS13025 (Asian lineage, Cambodia, 2010). Following infection, the animals were sampled (blood, urine, tears, and saliva), underwent daily health monitoring, and were exposed to Ae. aegypti at specified time points. All four animals developed viremia, which peaked 3–4 days post-infection at a maximum value of 6.9 log10 genome copies/mL. No virus was detected in urine, tears, or saliva. Infection by ZIKV caused minimal overt disease: serum biochemistry and CBC values largely fell within the normal ranges, and cytokine elevations were minimal. Strikingly, the minimally colonized population of Ae. aegypti exposed to viremic animals demonstrated a maximum infection rate of 26% during peak viremia, with two of the four macaques failing to infect a single mosquito at any time point. These data indicate that cynomolgus macaques may be an effective model for ZIKV infection of humans and highlights the relative refractoriness of Ae. aegypti for ZIKV infection at the levels of viremia observed.

Highlights

Zika virus (ZIKV), a mosquito-borne virus of the family Flaviviridae, was originally discovered in 1947 from the blood of a febrile sentinel rhesus macaque from Uganda’s Ziika forest [1]
PRNT50 assays performed on pre-exposure revealed all non-human primates (NHPs) maintained a neutralizing antibody response against chikungunya virus (CHIKV) (PRNT50 ≥ 640) but no existing neutralizing response against ZIKV (PRNT50 < 20), while terminal serum demonstrated that all animals underwent seroconversion (ZIKV PRNT50 titers of 1:20 in macaques 13428 and 13367, 1:40 in macaque 13422 and 1:80 in macaque 150844)
Some rectal temperatures were low during the first 12 dpi (Figure 3b), as previously demonstrated in immunocompromised mice infected with ZIKV [82], as well as in bonnet monkeys (Macaca radiatata) infected with DENV4 [83]

Summary

Introduction

Zika virus (ZIKV), a mosquito-borne virus of the family Flaviviridae, was originally discovered in 1947 from the blood of a febrile sentinel rhesus macaque from Uganda’s Ziika forest [1]. Based on early animal models [2] and laboratory infection of a human volunteer [3], ZIKV appeared to cause only. The scant number of human infections reported in the medical literature suggested that, in Africa, ZIKV circulated only in a sylvatic, enzootic cycle, in which forest-dwelling mosquitoes such as Aedes (Stegomyia) africanus Theobald and Ae. ZIKV may have been circulating in Southeast Asia as early as the 1950s [9,10,11], it was not associated with reports of clinical disease. Due to co-circulation of other flaviviruses in Southeast Asia (dengue [DENV], West Nile [WNV], Japanese encephalitis [JEV], etc.), it is hypothesized that cross-reactive immunity in this population forestalled extensive ZIKV outbreaks [7,9,12]. Following the 2007 outbreaks, ZIKV spread across the islands of the South Pacific, akin to the spread of chikungunya virus (CHIKV) [15]

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