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

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.

Durability and correlates of vaccine protection against Zika virus in rhesus monkeys

“…Virus was detected for a longer period of time in certain tissue compartments of the sham controls, including cerebrospinal fluid (CSF) and lymph nodes (LN) (Fig. 3C–D), consistent with previous findings from our laboratory and others (20–23). In contrast, PIV vaccinated monkeys showed no detectable viremia (<2 log copies/ml) in 75% (6 of 8) of animals (P=0.007 compared with sham controls), and low and transient viral blips in 25% (2 of 8) of animals.…”

Existing drugs as broad-spectrum and potent inhibitors for Zika virus by targeting NS2B-NS3 interaction

“…Prolonged excretion of ZIKV in sperm and urine has also been reported [67,68]. It is currently not known how long our studied drugs may be effective pi.…”

Infection via mosquito bite alters Zika virus replication kinetics in rhesus macaques

“…Needle inoculation remains an important option when it is 242 necessary to control the exact dose delivered, but the dose and number of sc inoculations could 243 alter virus distribution and replication kinetics. For example, several recent studies using needle 244 inoculation detected a broad ZIKV RNA tissue distribution, including in reproductive organs, the 245 CNS, and brain 7,26,36,37 . Likewise, we also found evidence of ZIKV infection of the brain and eye 246 in our needle inoculated animals.…”

“…Subcutaneous inoculation, 264 by contrast, likely resulted in slower dissemination through the draining lymph nodes; 265 dissemination may be slower still following mosquito infection, as indicated by the delay in peak 266 viral loads observed with mosquito-bite delivery of virus in this study. In addition, the use of 267 multiple simultaneous injections 36 could iatrogenically cause disease signs 17 . For example, the 268 fever response observed with multiple injections might be expected, given that injection of virus 269 stocks also delivers cell culture medium components that might serve as irritants; needle 270 puncture of the skin is also more traumatic than insertion of a mosquito proboscis.…”