Abstract
Lujo virus (LUJV) is a novel member of the Arenaviridae family that was first identified in 2008 after an outbreak of severe hemorrhagic fever (HF). In what was a small but rapidly progressing outbreak, this previously unknown virus was transmitted from the critically ill index patient to 4 attending healthcare workers. Four persons died during this outbreak, for a total case fatality of 80% (4/5). The suspected rodent source of the initial exposure to LUJV remains a mystery. Because of the ease of transmission, high case fatality, and novel nature of LUJV, we sought to establish an animal model of LUJV HF. Initial attempts in mice failed, but infection of inbred strain 13/N guinea pigs resulted in lethal disease. A total of 41 adult strain 13/N guinea pigs were infected with either wild-type LUJV or a full-length recombinant LUJV. Results demonstrated that strain 13/N guinea pigs provide an excellent model of severe and lethal LUJV HF that closely resembles what is known of the human disease. All infected animals experienced consistent weight loss (3–5% per day) and clinical illness characterized by ocular discharge, ruffled fur, hunched posture, and lethargy. Uniform lethality occurred by 11–16 days post-infection. All animals developed disseminated LUJV infection in various organs (liver, spleen, lung, and kidney), and leukopenia, lymphopenia, thrombocytopenia, coagulopathy, and elevated transaminase levels. Serial euthanasia studies revealed a temporal pattern of virus dissemination and increasing severity of disease, primarily targeting the liver, spleen, lungs, and lower gastrointestinal tract. Establishing an animal LUJV model is an important first step towards understanding the high pathogenicity of LUJV and developing vaccines and antiviral therapeutic drugs for this highly transmissible and lethal emerging pathogen.
Highlights
Beginning in the 1930s, novel pathogenic arenaviruses have been increasingly recognized as emerging threats to human health [1,2,3,4,5,6,7,8,9,10]
Limited data available from these patients indicated that Lujo virus (LUJV) hemorrhagic fever (HF) was characterized by thrombocytopenia, elevated liver transaminases, coagulopathy, viral antigen in multiple tissues, neurological symptoms in some cases, and eventual death
The pathogenic arenaviruses are a diverse group of human pathogens capable of causing a wide range of human illness ranging from encephalitis to severe hemorrhagic fever throughout the New and Old World
Summary
Beginning in the 1930s, novel pathogenic arenaviruses have been increasingly recognized as emerging threats to human health [1,2,3,4,5,6,7,8,9,10]. During the 1960s and 1970s, several previously unknown arenaviruses emerged as a significant public health threats and causes of a severe and often fatal human hemorrhagic fever (HF) syndrome. In 2008, Lujo virus (LUJV), a novel member of the family Arenaviridae, was first identified after an outbreak of severe HF in southern Africa [11]. During this outbreak, the index patient was transported by air from Lusaka, Zambia, to a private hospital in Johannesburg, South Africa, giving the virus its name, Lu-Jo. The index patient died from the infection approximately 12 days after the onset of the presumed first symptoms, and 2 days after hospitalization in Johannesburg. After a period of 10–13 days of progressively severe illness, 3 of these individuals died, resulting in a total case fatality of 80% (4/5)
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