Abstract
Limited availability of Indian rhesus macaques (IRM) is a bottleneck to study Zika virus (ZIKV) pathogenesis and evaluation of appropriate control measures in non-human primates. To address these issues, we report here the Mauritian cynomolgus macaque (MCM) model for ZIKV infection. In brief, six MCMs (seronegative for Dengue and ZIKV) were subdivided into three cohorts with a male and female each and challenged with different doses of Asian [PRVABC59 (Puerto Rico) or FSS13025 (Cambodia)] or African (IBH30656) lineage ZIKV isolates. Clinical signs were monitored; and biological fluids (serum, saliva, and urine) and tissues (testes and brain) were assessed for viral load by quantitative reverse transcription polymerase chain reaction and neutralizing antibodies (Nab) by 50% Plaque Reduction Neutralization Test (PRNT50) at various times post-infection (p.i). PRVABC59 induced viremia detectable up to day 10, with peak viral load at 2–3 days p.i. An intermittent viremia spike was observed on day 30 with titers reaching 2.5 × 103 genomes/mL. Moderate viral load was observed in testes, urine and saliva. In contrast, FSS13025 induced viremia lasting only up to 6 days and detectable viral loads in testes but not in urine and saliva. Recurrent viremia was detected but at lower titers compare to PRVABC59. Challenge with either PRVABC59 or FSS13025 resulted in 100% seroconversion; with mean PRNT50 titers ranging from 597 to 5179. IBH30656 failed to establish infection in MCM suggesting that MCM are susceptible to infection with ZIKV isolates of the Asian lineage but not from Africa. Due to the similarity of biphasic viremia and Nab responses between MCM and IRM models, MCM could be a suitable alternative for evaluation of ZIKV vaccine and therapeutic candidates.
Highlights
Zika virus (ZIKV) is a flavivirus transmitted primarily through mosquitos, first reported in 1947
Arthropod-borne viruses such as the flaviviruses continue to pose a significant threat to global health
The significance of ZIKV is highlighted in the infection associated complications, such as Guillain–Barre syndrome (Oehler et al, 2014; do Rosario et al, 2016) and the risk of vertical transmission of the virus from mother to the fetus, which can result in devastating lifelong neurological complications including microcephaly (Brasil and Nielsen-Saines, 2016; Martines et al, 2016; Mlakar et al, 2016; Sarno et al, 2016)
Summary
Zika virus (ZIKV) is a flavivirus transmitted primarily through mosquitos, first reported in 1947 (reviewed in Plourde and Bloch, 2016). Though apparent clinical symptoms are reported only in 20% of the infected patients, the disease associated complications such as microcephaly in newborn children and neurological manifestations (Guillain–Barre syndrome) make ZIKV a major health concern. Considering the rapid spread and the associated disease complications, the World Health Organization (WHO) has recently declared ZIKV as a global health emergency. This health scare is compounded by the lack of effective prophylactic and therapeutic measures.
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