Development of a New Tacaribe Arenavirus Infection Model and Its Use to Explore Antiviral Activity of a Novel Aristeromycin Analog

Background A growing number of arenaviruses can cause a devastating viral hemorrhagic fever (VHF) syndrome. They pose a public health threat as emerging viruses and because of their potential use as bioterror agents. All of the highly pathogenic New World arenaviruses (NWA) phylogenetically segregate into clade B and require maximum biosafety containment facilities for their study. Tacaribe virus (TCRV) is a nonpathogenic member of clade B that is closely related to the VHF arenaviruses at the amino acid level. Despite this relatedness, TCRV lacks the ability to antagonize the host interferon (IFN) response, which likely contributes to its inability to cause disease in animals other than newborn mice. Methodology/Principal Findings Here we describe a new mouse model based on TCRV challenge of AG129 IFN-α/β and -γ receptor-deficient mice. Titration of the virus by intraperitoneal (i.p.) challenge of AG129 mice resulted in an LD50 of ∼100 fifty percent cell culture infectious doses. Virus replication was evident in the serum, liver, lung, spleen, and brain 4–8 days after inoculation. MY-24, an aristeromycin derivative active against TCRV in cell culture at 0.9 µM, administered i.p. once daily for 7 days, offered highly significant (P\u3c0.001) protection against mortality in the AG129 mouse TCRV infection model, without appreciably reducing viral burden. In contrast, in a hamster model of arenaviral hemorrhagic fever based on challenge with clade A Pichinde arenavirus, MY-24 did not offer significant protection against mortality. Conclusions/Significance MY-24 is believed to act as an inhibitor of S-adenosyl-L-homocysteine hydrolase, but our findings suggest that it may ameliorate disease by blunting the effects of the host response that play a role in disease pathogenesis. The new AG129 mouse TCRV infection model provides a safe and cost-effective means to conduct early-stage pre-clinical evaluations of candidate antiviral therapies that target clade B arenaviruses

Biological flora of Central europe: Baldellia ranunculoides (Alismataceae)

Baldellia ranunculoides (L.) Parl. (Alismataceae) is a taxonomically problematic aquatic plant with an historically ill-defined distribution and global conservation status. This paper finds morphological, ecological and molecular evidence for two distinct taxa, probably best described as subspecies: (1) B. ranunculoides subsp. ranunculoides and (2) B. ranunculoides subsp. repens and provides detailed distribution data on their overlapping range, in different habitats, across the cool, high rainfall areas of western Europe and west Mediterranean. The two subspecies are amongst the relatively large number of threatened European and north Africa aquatic plants and this paper provides a systematic review of their relative conservation pressures and management needs, with particular emphasis on the status of both taxa in central Europe. Other observations indicate probable evolutionary relationships within B. ranunculoides s.l. and its associated taxa and the review points out where these and other research topics could potentially be pursued

A Taxonomic Revision of Dicoma (Asteraceae: Cichorioideae: Mustisieae) for the Horn of Africa

Volume: 85Start Page: 440End Page: 45