High susceptibility, viral dynamics and persistence of South American Zika virus in New World monkey species

Abstract

South American Zika virus (ZIKV) recently emerged as a novel human pathogen, linked with neurological disorders. However, comparative ZIKV infectivity studies in New World primates are lacking. Two members of the Callitrichidae family, common marmosets (Callithrix jacchus) and red-bellied tamarins (Saguinus labiatus), were highly susceptible to sub-cutaneous challenge with the Puerto Rico-origin ZIKVPRVABC59 strain. Both exhibited rapid, high, acute viraemia with early neuroinvasion (3 days) in peripheral and central nervous tissue. ZIKV RNA levels in blood and tissues were significantly higher in New World hosts compared to Old World species (Macaca mulatta, Macaca fascicularis). Tamarins and rhesus macaques exhibited loss of zonal occludens-1 (ZO-1) staining, indicative of a compromised blood-brain barrier 3 days post-ZIKV exposure. Early, widespread dissemination across multiple anatomical sites distant to the inoculation site preceded extensive ZIKV persistence after 100 days in New and Old World lineages, especially lymphoid, neurological and reproductive sites. Prolonged persistence in brain tissue has implications for otherwise resolved human ZIKV infection. High susceptibility of distinct New World species underscores possible establishment of ZIKV sylvatic cycles in primates indigenous to ZIKV endemic regions. Tamarins and marmosets represent viable New World models for ZIKV pathogenesis and therapeutic intervention studies, including vaccines, with contemporary strains.

Persistence of Anti-Zika Virus Immunoglobulin M Antibodies in Children with Microcephaly up to Four Years after Primary Infection

“…Investigation of ZIKV deposits in tissues revealed that primates infected subcutaneously with ZIKV presented detectable viral RNA over 60 days in the central and peripheral neuronal tissues, and other deposits have been already described in the for Rhesus macaque and Redbellied tamarin infected models (12).…”

Survey on Non-Human Primates and Mosquitoes Does not Provide Evidences of Spillover/Spillback between the Urban and Sylvatic Cycles of Yellow Fever and Zika Viruses Following Severe Outbreaks in Southeast Brazil

“…Due to similarities in natural history between YFV and ZIKV, concerns have grown about the possibility of ZIKV establishing a sylvatic cycle in Brazil, which would prevent its eradication, as happened with YFV [4]. Although ZIKV has never been isolated from any other vertebrate besides humans in the Americas, and sylvatic NHP-biting mosquitoes have never been detected to be naturally infected with ZIKV, the findings of RNA fragments compatible with ZIKV and antibodies against this virus in synanthropic marmosets and capuchin monkeys captured in peri urban areas in Brazil, and the demonstration that marmosets can experimentally sustain viremia [23][24][25] have led to the hypothesis that NHPs would play a role in sustaining the urban transmission cycle or in establishing an sylvatic transmission cycle in the Americas.…”

Passive immunisation of convalescent human anti-Zika plasma protects against challenge with New World Zika virus in cynomolgus macaques

“…International initiatives were established to better understand virus pathogenesis and develop strategies to combat future outbreaks. Studies conducted in different NHP species have elucidated pathogenesis whereby ZIKV is no longer regarded simply as a self-limiting acute infection but persisting viral signals have been detected in multiple anatomical sites many weeks after the initial infection has cleared from the blood [9][10][11][12][13][14][15][16] .…”

“…ZIKV has a broad host range capable of productively infecting a spectrum of higher mammals including humans and both Old and New World monkey species 16,17 . Antibody responses to major viral proteins (e.g., NS-1 and envelope antigens), particularly a broadly neutralising antibody response, are associated with recovery from ZIKV infection that appears to confer protective immunity against re-infection, with a lack of new infections in exposed, immune populations as confirmed by epidemiological studies 18 .…”

“…Immunodeficient mouse models remain informative despite lacking the ability to fully recapitulate systemic ZIKV infection of immunocompetent hosts, to provide indications of vaccine efficacy 22 . However, due to anatomical differences between NHPs and rodents, including differences in placental structure, comparative pathogenesis studies conducted in multiple NHP species, including New World hosts, suggest higher order mammals may more faithfully reproduce human ZIKV infection and associated immune responses 16,17 .…”