A Novel Rhabdovirus Associated with Acute Hemorrhagic Fever in Central Africa

Deep sequencing was used to discover a novel rhabdovirus (Bas-Congo virus, or BASV) associated with a 2009 outbreak of 3 human cases of acute hemorrhagic fever in Mangala village, Democratic Republic of Congo (DRC), Africa. The cases, presenting over a 3-week period, were characterized by abrupt disease onset, high fever, mucosal hemorrhage, and, in two patients, death within 3 days. BASV was detected in an acute serum sample from the lone survivor at a concentration of 1.09×106 RNA copies/mL, and 98.2% of the genome was subsequently de novo assembled from ∼140 million sequence reads. Phylogenetic analysis revealed that BASV is highly divergent and shares less than 34% amino acid identity with any other rhabdovirus. High convalescent neutralizing antibody titers of >1∶1000 were detected in the survivor and an asymptomatic nurse directly caring for him, both of whom were health care workers, suggesting the potential for human-to-human transmission of BASV. The natural animal reservoir host or arthropod vector and precise mode of transmission for the virus remain unclear. BASV is an emerging human pathogen associated with acute hemorrhagic fever in Africa.

[1]  Maxim Teslenko,et al.  MrBayes 3.2: Efficient Bayesian Phylogenetic Inference and Model Choice Across a Large Model Space , 2012, Systematic biology.

[2]  P. Formenty,et al.  Emergence of divergent Zaire ebola virus strains in Democratic Republic of the Congo in 2007 and 2008. , 2011, The Journal of infectious diseases.

[3]  Nuno A. Fonseca,et al.  Assemblathon 1: a competitive assessment of de novo short read assembly methods. , 2011, Genome research.

[4]  Aneta J. Gubala,et al.  Tibrogargan and Coastal Plains rhabdoviruses: genomic characterization, evolution of novel genes and seroprevalence in Australian livestock. , 2011, The Journal of general virology.

[5]  S. Mendoza,et al.  Cross-Species Transmission of a Novel Adenovirus Associated with a Fulminant Pneumonia Outbreak in a New World Monkey Colony , 2011, PLoS pathogens.

[6]  J. Gonzalez,et al.  Ebola and Marburg haemorrhagic fever viruses: major scientific advances, but a relatively minor public health threat for Africa. , 2011, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[7]  S. Whelan,et al.  A Recombinant Vesicular Stomatitis Virus Bearing a Lethal Mutation in the Glycoprotein Gene Uncovers a Second Site Suppressor That Restores Fusion , 2011, Journal of Virology.

[8]  J. Patterson,et al.  Vaccines against viral hemorrhagic fevers: Non-human primate models , 2011, Human vaccines.

[9]  Steve Miller,et al.  A Metagenomic Analysis of Pandemic Influenza A (2009 H1N1) Infection in Patients from North America , 2010, PloS one.

[10]  V. Arankalle,et al.  Chandipura virus encephalitis outbreak among children in Nagpur division, Maharashtra, 2007. , 2010, The Indian journal of medical research.

[11]  C. Chiu,et al.  Metagenomics for the discovery of novel human viruses. , 2010, Future microbiology.

[12]  K. Kristiansen,et al.  SOAP2: an improved ultrafast tool for short read alignment , 2009, Bioinform..

[13]  C. Rupprecht,et al.  The rhabdoviruses: biodiversity, phylogenetics, and evolution. , 2009, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[14]  W. Ian Lipkin,et al.  Genetic Detection and Characterization of Lujo Virus, a New Hemorrhagic Fever–Associated Arenavirus from Southern Africa , 2009, PLoS pathogens.

[15]  R. Tesh,et al.  Nyamanini and Midway Viruses Define a Novel Taxon of RNA Viruses in the Order Mononegavirales , 2009, Journal of Virology.

[16]  D. Rogers,et al.  Risk Maps of Lassa Fever in West Africa , 2009, PLoS neglected tropical diseases.

[17]  E. Delwart,et al.  Metagenomic Analyses of Viruses in Stool Samples from Children with Acute Flaccid Paralysis , 2009, Journal of Virology.

[18]  A. Hyatt,et al.  Genomic characterisation of Wongabel virus reveals novel genes within the Rhabdoviridae. , 2008, Virology.

[19]  T. Monath.  Dengue and yellow fever--challenges for the development and use of vaccines. , 2007, The New England journal of medicine.

[20]  M. Turchi,et al.  Evaluation of a Commercial Real-Time PCR Kit for Detection of Dengue Virus in Samples Collected during an Outbreak in Goiânia, Central Brazil, in 2005 , 2007, Journal of Clinical Microbiology.

[21]  Ö. Ergönül.  Crimean-Congo haemorrhagic fever , 2006, The Lancet Infectious Diseases.

[22]  M. Bray.  Pathogenesis of viral hemorrhagic fever. , 2005, Current opinion in immunology.

[23]  G. Darai,et al.  Characterization of the Tupaia Rhabdovirus Genome Reveals a Long Open Reading Frame Overlapping with P and a Novel Gene Encoding a Small Hydrophobic Protein , 2005, Journal of Virology.

[24]  David L. Swerdlow,et al.  Epidemiology of Escherichia coli O157:H7 Outbreaks, United States, 1982–2002 , 2005, Emerging infectious diseases.

[25]  K. Katoh,et al.  MAFFT version 5: improvement in accuracy of multiple sequence alignment , 2005, Nucleic acids research.

[26]  Peter B Jahrling,et al.  Exotic emerging viral diseases: progress and challenges , 2004, Nature Medicine.

[27]  T. Blanchard.  Rabies and other lyssavirus diseases , 2004, The Lancet.

[28]  Stuart T. Nichol,et al.  Rapid Diagnosis of Ebola Hemorrhagic Fever by Reverse Transcription-PCR in an Outbreak Setting and Assessment of Patient Viral Load as a Predictor of Outcome , 2004, Journal of Virology.

[29]  J. Wells,et al.  Epidemiology of sporadic bloody diarrhea in rural Western Kenya. , 2003, The American journal of tropical medicine and hygiene.

[30]  R. Kingston,et al.  Calcium Phosphate Transfection , 2003, Current protocols in cell biology.

[31]  N. Bean,et al.  Foodborne disease outbreaks in United States schools , 2002, The Pediatric infectious disease journal.

[32]  Luis L. Rodriguez,et al.  Emergence and re-emergence of vesicular stomatitis in the United States. , 2002, Virus research.

[33]  Philip K. Russell,et al.  Hemorrhagic fever viruses as biological weapons: medical and public health management. , 2002, JAMA.

[34]  W. J. Kent,et al.  BLAT--the BLAST-like alignment tool. , 2002, Genome research.

[35]  P. Debré,et al.  Human asymptomatic Ebola infection and strong inflammatory response , 2000, The Lancet.

[36]  R. Colebunders,et al.  Organization of patient care during the Ebola hemorrhagic fever epidemic in Kikwit, Democratic Republic of the Congo, 1995. , 1999, The Journal of infectious diseases.

[37]  M. Conti.  Vector relationships and other characteristics of barley yellow striate mosaic virus (BYSMV) , 1980 .

[38]  D. Stallknecht,et al.  Characterization of Durham virus, a novel rhabdovirus that encodes both a C and SH protein. , 2011, Virus research.

[39]  M. Egholm,et al.  Moussa virus: a new member of the Rhabdoviridae family isolated from Culex decens mosquitoes in Côte d'Ivoire. , 2010, Virus research.

[40]  B. Thiers,et al.  Clonal Integration of a Polyomavirus in Human Merkel Cell Carcinoma , 2009 .

[41]  Graziano Pesole,et al.  BMC Evolutionary Biology BioMed Central , 2007 .

[42]  B. Hoffmann,et al.  Fish rhabdoviruses: molecular epidemiology and evolution. , 2005, Current topics in microbiology and immunology.

[43]  Z. Fu.  Genetic comparison of the rhabdoviruses from animals and plants. , 2005, Current topics in microbiology and immunology.

[44]  Z. Fu.  The world of rhabdoviruses , 2005 .

[45]  Imported Lassa fever--New Jersey, 2004. , 2004, MMWR. Morbidity and mortality weekly report.