Rescue of a recombinant Machupo virus from cloned cDNAs and in vivo characterization in interferon (αβ/γ) receptor double knockout mice

从克隆的 cDNA 中拯救重组 Machupo 病毒并在干扰素 (αβ/γ) 受体双敲除小鼠中进行体内表征

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作者:Michael Patterson, Alexey Seregin, Cheng Huang, Olga Kolokoltsova, Jennifer Smith, Milagros Miller, Jeanon Smith, Nadezhda Yun, Allison Poussard, Ashley Grant, Bersabeh Tigabu, Aida Walker, Slobodan Paessler

Abstract

Machupo virus (MACV) is the etiological agent of Bolivian hemorrhagic fever (BHF), a reemerging and neglected tropical disease associated with high mortality. The prototypical strain of MACV, Carvallo, was isolated from a human patient in 1963, but minimal in vitro and in vivo characterization has been reported. To this end, we utilized reverse genetics to rescue a pathogenic MACV from cloned cDNAs. The recombinant MACV (rMACV) had in vitro growth properties similar to those of the parental MACV. Both viruses caused similar disease development in alpha/beta and gamma interferon receptor knockout mice, including neurological disease development and high mortality. In addition, we have identified a novel murine model with mortality and neurological disease similar to BHF disease reported in humans and nonhuman primates.

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