Max von Pettenkofer-Institute Virology & Gene Center, LMU Munich, 81377 Munich, Germany.
Department of Infectious Diseases, Molecular Virology, University of Heidelberg, 69120 Heidelberg, Germany.
Viruses. 2021 Aug 30;13(9):1726. doi: 10.3390/v13091726.
Lyssaviruses are neurotropic rhabdoviruses thought to be restricted to mammalian hosts, and to originate from bats. The identification of lyssavirus sequences from amphibians and reptiles by metatranscriptomics thus comes as a surprise and challenges the mammalian origin of lyssaviruses. The novel sequences of the proposed American tree frog lyssavirus (ATFLV) and anole lizard lyssavirus (ALLV) reveal substantial phylogenetic distances from each other and from bat lyssaviruses, with ATFLV being the most distant. As virus isolation has not been successful yet, we have here studied the functionality of the authentic ATFLV- and ALLV-encoded glycoproteins in the context of rabies virus pseudotype particles. Cryogenic electron microscopy uncovered the incorporation of the plasmid-encoded G proteins in viral envelopes. Infection experiments revealed the infectivity of ATFLV and ALLV G-coated RABV pp for a broad spectrum of cell lines from humans, bats, and reptiles, demonstrating membrane fusion activities. As presumed, ATFLV and ALLV G RABV pp escaped neutralization by human rabies immune sera. The present findings support the existence of contagious lyssaviruses in poikilothermic animals, and reveal a broad cell tropism in vitro, similar to that of the rabies virus.
纤毫病毒是神经嗜性的弹状病毒，被认为仅限于哺乳动物宿主，并且起源于蝙蝠。通过宏转录组学从两栖动物和爬行动物中鉴定出纤毫病毒序列，这令人惊讶，也挑战了纤毫病毒的哺乳动物起源。提出的美洲树蛙纤毫病毒（ATFLV）和安乐蜥纤毫病毒（ALLV）的新序列彼此之间以及与蝙蝠纤毫病毒之间存在很大的系统发育距离，ATFLV 是最远的。由于尚未成功分离病毒，我们在这里研究了狂犬病病毒假型颗粒中真实的 ATFLV 和 ALLV 编码糖蛋白的功能。低温电子显微镜揭示了质粒编码的 G 蛋白在病毒包膜中的掺入。感染实验表明，ATFLV 和 ALLV G 包裹的 RABV pp 能够感染来自人类、蝙蝠和爬行动物的广泛细胞系，表现出膜融合活性。如预期的那样，ATFLV 和 ALLV G RABV pp 逃避了人类狂犬病免疫血清的中和。目前的发现支持在变温动物中存在传染性纤毫病毒，并揭示了体外与狂犬病病毒相似的广泛细胞嗜性。
