Attenuation of Simian Varicella Virus Infection by Enhanced Green Fluorescent Protein in Rhesus Macaques.

作者: Ravi Mahalingam , Benedikt B. Kaufer , Werner J. D. Ouwendijk , Georges M. G. M. Verjans , Colin Coleman

DOI: 10.1128/JVI.02253-17

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摘要: Simian varicella virus (SVV), the primate counterpart of varicella-zoster virus, causes (chickenpox), establishes latency in ganglia, and reactivates to produce zoster. We previously demonstrated that a recombinant SVV expressing enhanced green fluorescent protein (rSVV.eGFP) is slightly attenuated both culture infected monkeys. Here, we generated two additional SVVs visualize cells vitro vivo One harbors eGFP fused N terminus open reading frame 9 (ORF9) (rSVV.eGFP-2a-ORF9), another C ORF66 (rSVV.eGFP-ORF66). Both viruses efficiently expressed cultured cells. infections were comparable wild-type (SVV.wt). Unlike SVV.wt, eGFP-tagged did not replicate rhesus culture. Intratracheal (i.t.) or i.t. plus intravenous (i.v.) inoculation macaques with these new resulted low viremia without rash, although DNA was abundant bronchoalveolar lavage (BAL) fluid at 10 days postinoculation (dpi). also found trigeminal ganglia one monkey inoculated rSVV.eGFP-ORF66. Intriguingly, humoral response observed. In addition, monkeys eGFP-expressing protected from superinfection suggesting had mounted an efficient immune response. Together, our results show expression could be responsible for their reduced pathogenesis.IMPORTANCE infection nonhuman primates has served as extremely useful animal model study (VZV) pathogenesis. are great tool investigate constructed tested inserted into different locations genome. showed robust replication but compared SVV.wt during primary macaques. Our indicate conclusions on based should handled care, since result attenuation virus.

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