Abstract
A monkey model of Zika virus (ZIKV) infection is urgently needed to better understand transmission and pathogenesis, given its proven association with fetal brain defects in pregnant women and acute neurological illness. Here we experimentally infected 4 male marmosets with ZIKV (prototype 1947 African strain) and monitored them clinically with sampling of various body fluids and tissues for nearly 3 months. We show that the course of acute infection with ZIKV in these New World monkeys resembles the human illness in many respects, including (1) lack of apparent clinical symptoms in most cases, (2) persistence of the virus in body fluids such as semen and saliva for longer periods of time than in serum, and (3) generation of neutralizing antibodies as well as an antiviral immunological host response. Importantly, ZIKV-infected saliva samples (in addition to serum) were found to be infectious, suggesting potential capacity for viral transmission by the oral route. Re-challenge of a previously infected marmoset with a contemporary outbreak strain SPH2015 from Brazil resulted in continued protection against infection, no viral shedding, and boosting of the immune response. Given the key similarities to human infection, a marmoset model of ZIKV infection may be useful for testing of new drugs and vaccines.
Highlights
The primary mode of Zika virus (ZIKV) transmission is via mosquito bite, it has been shown that the virus has the capacity for sexual transmission[7]
We found that male marmosets inoculated with ZIKV did not develop signs of clinical illness, mimicking the approximately 80% of human infections that are asymptomatic[4]
We show that immunity elicited by the prototype 1947 Uganda strain (MR766) protects against subsequent infection with a contemporary outbreak strain (2015SPH)
Summary
The primary mode of ZIKV transmission is via mosquito bite, it has been shown that the virus has the capacity for sexual transmission[7]. The virus has been detected for at least 2 weeks after symptom onset in saliva and urine samples from acutely infected individuals[9], it is unknown whether the sampled body fluids were infectious. Investigations with NHP can enable serial sampling and analyses of body fluids (e.g. urine, saliva, feces, and semen) that are impractical with rodent models. We present a marmoset model of acute ZIKV infection generated by inoculating 4 animals with ZIKV, followed by clinical monitoring and serial sampling for nearly 3 months. We sought to evaluate ZIKV infectivity, pathogenesis, persistence in infected body fluids and potential transmission risk, and production of neutralizing antibodies. The host response to acute ZIKV infection was investigated by lymphocyte phenotyping, cytokine analyses and global transcriptome profiling of blood from experimentally infected animals
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