heterologous protection against asian zika virus challenge in rhesus macaques.zika virus (zikv; flaviviridae, flavivirus) was declared a public health emergency of international concern by the world health organization (who) in february 2016, because of the evidence linking infection with zikv to neurological complications, such as guillain-barre syndrome in adults and congenital birth defects including microcephaly in the developing fetus. because development of a zikv vaccine is a top research priority and because the genetic and antigenic variability of many rna viruse ...201627911897
development of a zika virus infection model in cynomolgus 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 afr ...201628066354
the brazilian zika virus strain causes birth defects in experimental models.zika virus (zikv) is an arbovirus belonging to the genus flavivirus (family flaviviridae) and was first described in 1947 in uganda following blood analyses of sentinel rhesus monkeys. until the twentieth century, the african and asian lineages of the virus did not cause meaningful infections in humans. however, in 2007, vectored by aedes aegypti mosquitoes, zikv caused the first noteworthy epidemic on the yap island in micronesia. patients experienced fever, skin rash, arthralgia and conjunctiv ...027279226
the zika outbreak of the 21st century.the zika virus outbreak has captivated the attention of the global audience and information has spread rapidly and wildly through the internet and other media channels. this virus was first identified in 1947, when it was isolated from a sentinel rhesus monkey placed by british scientists working at the yellow fever research laboratory located in the zika forest area of uganda, hence its name, and is transmitted primarily by the mosquito vector, aedes aegypti. the fact that the rhesus macaque is ...201626925496
[zika virus: a review to clinicians].zika virus is a flavivirus related to dengue virus, yellow fever virus and west nile virus. it is considered an emerging arbovirus transmitted by mosquitos of the genus aedes. its first description took place in 1947 in the zika forest in uganda, isolated on rhesus monkey used as bait to study the yellow fever virus. sporadic cases have been detected in african countries and at the end of the 70's in indonesia. in 2007, epidemics were described in micronesia and other islands in the pacific ocea ...201626849762
zika virus tissue and blood compartmentalization in acute infection of rhesus macaques.animal models of zika virus (zikv) are needed to better understand tropism and pathogenesis and to test candidate vaccines and therapies to curtail the pandemic. humans and rhesus macaques possess similar fetal development and placental biology that is not shared between humans and rodents. we inoculated 2 non-pregnant rhesus macaques with a 2015 brazilian zikv strain. consistent with most human infections, the animals experienced no clinical disease but developed short-lived plasma viremias tha ...201728141843
zika virus in asia.zika virus (zikv) is an emerging mosquito-borne virus that was first isolated from a sentinel rhesus monkey in the zika forest in uganda in 1947. in asia, the virus was isolated in malaysia from aedes aegypti mosquitoes in 1966, and the first human infections were reported in 1977 in central java, indonesia. in this review, all reported cases of zikv infection in asia as of september 1, 2016 are summarized and some of the hypotheses that could currently explain the apparently low incidence of zi ...201727939768
understanding zika virus.this article describes what pediatric healthcare professionals should know about zika virus (zikv).201727862959
zika virus update ii: recent development of animal models-proofs of association with human pathogenesis.three recent studies in pregnant mice and one ongoing study in rhesus macaques evaluating the effect of zikv infection have provided important information about maternal-fetus transmission and zikv-related pathogenesis, confirming a causal role of zikv in neurological problems observed in humans. here, we present an update of these works published in the past few weeks. j. med. virol. 88:1657-1658, 2016. © 2016 wiley periodicals, inc.201627208545
zika virus: yet another emerging threat to nepal.zika virus (zikv) is a flavivirus with single stranded rna related to yellow fever, dengue, west nile, and japanese encephalitis viruses and is transmitted by aedes mosquitoes primarily by aedes aegipti which is widely distributed in nepal. zikv was first identified incidentally in rhesus monkey in uganda in 1947 and human infection in 1952; and by now outbreaks of zikv disease have been recorded in africa, the americas, asia and the pacific. the world health organization (who) has recently decl ...201627005721
the convergence of a virus, mosquitoes, and human travel in globalizing the zika epidemic.the zika virus was first identified in 1947 in the zika forest of uganda. it was discovered in a rhesus monkey that had been placed in a cage on a sentinel platform in the forest by the virus research institute. when this writer visited the institute and the zika forest in 1961, work was underway to identify mosquito species at various levels of the tree canopy. this was done through the placement of traps at various levels of a 120-foot-high steel tower which this writer climbed. at that time, ...201626969497
a rhesus macaque model of asian-lineage zika virus infection.infection with asian-lineage zika virus (zikv) has been associated with guillain-barré syndrome and fetal abnormalities, but the underlying mechanisms remain poorly understood. animal models of infection are thus urgently needed. here we show that rhesus macaques are susceptible to infection by an asian-lineage zikv closely related to strains currently circulating in the americas. following subcutaneous inoculation, zikv rna is detected in plasma 1 day post infection (d.p.i.) in all animals (n=8 ...201627352279
high infection rates for adult macaques after intravaginal or intrarectal inoculation with zika virus.unprotected sexual intercourse between persons residing in or traveling from regions with zika virus transmission is a risk factor for infection. to model risk for infection after sexual intercourse, we inoculated rhesus and cynomolgus macaques with zika virus by intravaginal or intrarectal routes. in macaques inoculated intravaginally, we detected viremia and virus rna in 50% of macaques, followed by seroconversion. in macaques inoculated intrarectally, we detected viremia, virus rna, or both, ...201728548637
zika virus: history of a newly emerging arbovirus.zika virus was originally identified in a sentinel rhesus monkey in the zika forest of uganda in 1947. the virus is a member of the family flaviviridae, genus flavivirus, and is transmitted to humans by aedes species mosquitoes. the first report of zika virus outside africa and asia was in 2007 when the virus was associated with a small outbreak in yap state, part of the federated states of micronesia. since then, zika virus infections have been reported around the world, including in southeast ...201627282424
protective efficacy of multiple vaccine platforms against zika virus challenge in rhesus monkeys.zika virus (zikv) is responsible for a major ongoing epidemic in the americas and has been causally associated with fetal microcephaly. the development of a safe and effective zikv vaccine is therefore an urgent global health priority. here we demonstrate that three different vaccine platforms protect against zikv challenge in rhesus monkeys. a purified inactivated virus vaccine induced zikv-specific neutralizing antibodies and completely protected monkeys against zikv strains from both brazil a ...201627492477
zika virus: a new threat to human reproduction.zika virus (zikv) was first isolated in 1947 in a rhesus monkey from the zika forest of uganda. until 2007, only 14 human cases were reported. the first large human outbreak occurred in 2007 (yap island, federated states of micronesia, pacific) followed by french polynesia in 2013 and brazil in 2015. the virus is mainly transmitted through aedes mosquito bites, but sexual and post-transfusion transmissions have been reported. symptoms include low-grade fever, maculopapular rash, conjunctivitis, ...201727966802
zika virus infection of rhesus macaques leads to viral persistence in multiple tissues.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 ...201728278237
25-hydroxycholesterol protects host against zika virus infection and its associated microcephaly in a mouse model.zika virus (zikv) has become a public health threat due to its global transmission and link to severe congenital disorders. the host immune responses to zikv infection have not been fully elucidated, and effective therapeutics are not currently available. herein, we demonstrated that cholesterol-25-hydroxylase (ch25h) was induced in response to zikv infection and that its enzymatic product, 25-hydroxycholesterol (25hc), was a critical mediator of host protection against zikv. synthetic 25hc addi ...201728314593
correction: zika virus infection of rhesus macaques leads to viral persistence in multiple tissues.[this corrects the article doi: 10.1371/journal.ppat.1006219.].201728380070
characterization of a 2016 clinical isolate of zika virus in non-human primates.animal models are critical to understand disease and to develop countermeasures for the ongoing epidemics of zika virus (zikv). here we report a non-human primate model using a 2016 contemporary clinical isolate of zikv. upon subcutaneous inoculation, rhesus macaques developed fever and viremia, with robust excretion of zikv rna in urine, saliva, and lacrimal fluid. necropsy of two infected animals revealed that systematic infections involving central nervous system and visceral organs were esta ...201627693104
highly efficient maternal-fetal zika virus transmission in pregnant rhesus macaques.infection with zika virus (zikv) is associated with human congenital fetal anomalies. to model fetal outcomes in nonhuman primates, we administered asian-lineage zikv subcutaneously to four pregnant rhesus macaques. while non-pregnant animals in a previous study contemporary with the current report clear viremia within 10-12 days, maternal viremia was prolonged in 3 of 4 pregnancies. fetal head growth velocity in the last month of gestation determined by ultrasound assessment of head circumferen ...201728542585
zika virus pathogenesis in rhesus macaques is unaffected by pre-existing immunity to dengue virus.zika virus (zikv) is a re-emerging virus that has recently spread into dengue virus (denv) endemic regions and cross-reactive antibodies (abs) could potentially affect zikv pathogenesis. using denv-immune serum, it has been shown in vitro that antibody-dependent enhancement (ade) of zikv infection can occur. here we study the effects of pre-existing denv immunity on zikv infection in vivo. we infect two cohorts of rhesus macaques with zikv; one cohort has been exposed to denv 2.8 years earlier a ...201728643775
immune cell dynamics in rhesus macaques infected with a brazilian strain of zika virus.zika virus (zikv) is a mosquito-borne and sexually transmitted flavivirus that is associated with fetal cns-damaging malformations during pregnancy in humans. this study documents the viral kinetics and immune responses in rhesus macaques infected with a clinical zikv brazilian isolate. we evaluated the viral kinetics and immune responses induced after an i.v. infection with a brazilian zikv clinical isolate (hs-2015-ba-01) in rhesus macaques for up to 142 d. zikv-specific ab-secreting cells, ge ...201728667164
zika virus preferentially replicates in the female reproductive tract after vaginal inoculation of rhesus macaques.zika virus (zikv) is a mosquito-transmitted virus that can cause severe defects in an infected fetus. zikv is also transmitted by sexual contact, although the relative importance of sexual transmission is unclear. to better understand the role of sexual transmission in zikv pathogenesis, a nonhuman primate (nhp) model of vaginal transmission was developed. zikv was readily transmitted to mature cycling female rhesus macaque (rm) by vaginal inoculation with 104-106 plaque-forming units (pfu). how ...201728746373
macaque monkeys in zika virus research: 1947-present.zika virus was first isolated in 1947 from an exotic rhesus macaque. nearly 70 years later, the emergence of zika virus in the americas and its newly described association with birth defects has motivated the development of captive macaque monkey models of human zika virus infection. this review describes similarities between macaque and human zika virus pathogenesis and discusses specific advantages and disadvantages of using macaques instead of other laboratory animal models. in particular, ma ...201728750247
oropharyngeal mucosal transmission of zika virus in rhesus macaques.zika virus is present in urine, saliva, tears, and breast milk, but the transmission risk associated with these body fluids is currently unknown. here we evaluate the risk of zika virus transmission through mucosal contact in rhesus macaques. application of high-dose zika virus directly to the tonsils of three rhesus macaques results in detectable plasma viremia in all animals by 2 days post-exposure; virus replication kinetics are similar to those observed in animals infected subcutaneously. th ...201728765581
impact of prior flavivirus immunity on zika virus infection in rhesus macaques.studies have demonstrated cross-reactivity of anti-dengue virus (denv) antibodies in human sera against zika virus (zikv), promoting increased zikv infection in vitro. however, the correlation between in vitro and in vivo findings is not well characterized. thus, we evaluated the impact of heterotypic flavivirus immunity on zikv titers in biofluids of rhesus macaques. animals previously infected (≥420 days) with denv2, denv4, or yellow fever virus were compared to flavivirus-naïve animals follow ...201728771605
emerging zika virus disease: a public health emergency of global concern.infectious diseases remain a leading source of human morbidity and mortality. recently, emerging infectious diseases are dominated by zoonoses, and eventually rising considerably. their emergence is dependent on various factors especially, socioeconomic, environmental and ecological factors etc. recently, the swift spread of zika virus (zikv) through the americas, simultaneously with the association of infection with microcephaly and guillain-barré syndrome, has strained this previously overlook ...201628466030
zika virus persistence in the central nervous system and lymph nodes of rhesus monkeys.zika virus (zikv) is associated with severe neuropathology in neonates as well as guillain-barré syndrome and other neurologic disorders in adults. prolonged viral shedding has been reported in semen, suggesting the presence of anatomic viral reservoirs. here we show that zikv can persist in cerebrospinal fluid (csf) and lymph nodes (ln) of infected rhesus monkeys for weeks after virus has been cleared from peripheral blood, urine, and mucosal secretions. zikv-specific neutralizing antibodies co ...201728457610
evolving rna virus pandemics: hiv, hcv, ebola, dengue, chikunguya, and now zika!the zika virus (zikv), a flavivirus related to yellow fever, dengue, and west nile, originated in the zika forest in uganda and was discovered in a rhesus monkey in 1947. the disease now has "explosive" pandemic potential, with outbreaks in africa, southeast asia, the pacific islands, and the americas. to date, the cdc has issued travel alerts for at least 30 countries and territories in latin america, the caribbean, polynesia, and cape verde in africa.201627028271
prior exposure to zika virus significantly enhances peak dengue-2 viremia in rhesus macaques.structural and functional homologies between the zika and dengue viruses' envelope proteins raise the possibility that cross-reactive antibodies induced following zika virus infection might enhance subsequent dengue infection. using the rhesus macaque model we show that prior infection with zika virus leads to a significant enhancement of dengue-2 viremia that is accompanied by neutropenia, lympocytosis, hyperglycemia, and higher reticulocyte counts, along with the activation of pro-inflammatory ...201728874759
a new threat to human reproduction system posed by zika virus (zikv): from clinical investigations to experimental studies.zika virus (zikv) was first isolated in 1947 from a rhesus monkey in the zika forest of uganda. zikv has since been silently circulating in a number of equatorial countries for over 50 years. the largest outbreak in humans occurred in brazil in 2015-2016. unlike its flavivirus relatives, sexual and post-transfusion transmissions of zikv have been reported. in addition, fetal infection can result in microcephaly and congenital zikv syndrome has been reported in neonates. moreover, zikv rna can pe ...201728893652
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