Genetic Detection and Characterization of Lujo Virus, a New Hemorrhagic Fever–Associated Arenavirus from Southern Africa

Thomas Briese,Jacqueline Weyer,Craig Street,Robert Swanepoel,Marina L Khristova,Stuart T Nichol,W Ian Lipkin,Michael Egholm,Gustavo Palacios,Laura K Mcmullan,Stephen K Hutchison,Janusz T Paweska

doi:10.1371/journal.ppat.1000455

Thomas Briese, Jacqueline Weyer + Show 10 more

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https://doi.org/10.1371/journal.ppat.1000455

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Lujo virus (LUJV), a new member of the family Arenaviridae and the first hemorrhagic fever–associated arenavirus from the Old World discovered in three decades, was isolated in South Africa during an outbreak of human disease characterized by nosocomial transmission and an unprecedented high case fatality rate of 80% (4/5 cases). Unbiased pyrosequencing of RNA extracts from serum and tissues of outbreak victims enabled identification and detailed phylogenetic characterization within 72 hours of sample receipt. Full genome analyses of LUJV showed it to be unique and branching off the ancestral node of the Old World arenaviruses. The virus G1 glycoprotein sequence was highly diverse and almost equidistant from that of other Old World and New World arenaviruses, consistent with a potential distinctive receptor tropism. LUJV is a novel, genetically distinct, highly pathogenic arenavirus.

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Members of the genus Arenavirus, comprising currently 22 recognized species, are divided into two complexes based on serologic, genetic, and geographic relationships [1,2]: the New World (NW) or Tacaribe complex, and the Old World (OW) or Lassa-Lymphocytic choriomeningitis complex that includes the ubiquitous arenavirus type-species Lymphocytic choriomeningitis virus (LCMV; [3])
With the possible exception of NW Tacaribe virus (TCRV; [12]), which has been isolated from bats (Artibeus spp.), individual arenavirus species are commonly transmitted by specific rodent species wherein the capacity for persistent infection without overt disease suggests long evolutionary adaptation between the agent and its host [1,13,14,15,16]
Whereas NW arenaviruses are associated with rodents in the Sigmodontinae subfamily of the family Cricetidae, OW arenaviruses are associated with rodents in the Murinae subfamily of the family Muridae

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Members of the genus Arenavirus, comprising currently 22 recognized species (http://www.ictvonline.org/virusTaxonomy. asp?version=2008), are divided into two complexes based on serologic, genetic, and geographic relationships [1,2]: the New World (NW) or Tacaribe complex, and the Old World (OW) or Lassa-Lymphocytic choriomeningitis complex that includes the ubiquitous arenavirus type-species Lymphocytic choriomeningitis virus (LCMV; [3]). The RNA genome of arenaviruses is bi-segmented, comprising a large (L) and a small (S) segment that each codes for two proteins in ambisense coding strategy [4,5] Despite this coding strategy, the Arenaviridae are classified together with the families Orthomyxoviridae and Bunyaviridae as segmented singlestrand, negative sense RNA viruses. The South American hemorrhagic fever viruses Junin (JUNV; [6,7]), Machupo (MACV; [8]), Guanarito (GTOV; [9]) and Sabia virus (SABV, [10]), and the African Lassa virus (LASV [11]), are restricted to biosafety level 4 (BSL-4) containment due to their associated aerosol infectivity and rapid onset of severe disease. LCMV, which is spread by the ubiquitous Mus musculus as host species and found world-wide, causes symptoms in humans that range from asymptomatic infection or mild febrile illness to meningitis and encephalitis [13]. Three other African arenaviruses are not known to cause human disease: Ippy virus (IPPYV; [22,23]), isolated from

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