Marburgvirus genomics and association with a large hemorrhagic fever outbreak in Angola

Jonathan S. Towner, Marina L. Khristova, Tara K. Sealy, Martin J. Vincent, Bobbie R. Erickson, Darcy A. Bawiec, Amy L. Hartman, James A. Comer, Sherif R. Zaki, Ute Ströher, Filomena Gomes Da Silva, Fernando Del Castillo, Pierre E. Rollin, Thomas Ksiazek, Stuart T. Nichol

Research output: Contribution to journalArticle

194 Citations (Scopus)

Abstract

In March 2005, the Centers for Disease Control and Prevention (CDC) investigated a large hemorrhagic fever (HF) outbreak in Uige Province in northern Angola, West Africa. In total, 15 initial specimens were sent to CDC, Atlanta, Ga., for testing for viruses associated with viral HFs known to be present in West Africa, including ebolavirus. Marburgvirus was also included despite the fact that the origins of all earlier outbreaks were linked directly to East Africa. Surprisingly, marburgvirus was confirmed (12 of 15 specimens) as the cause of the outbreak. The outbreak likely began in October 2004 and ended in July 2005, and it included 252 cases and 227 (90%) fatalities (report from the Ministry of Health, Republic of Angola, 2005), making it the largest Marburg HF outbreak on record. A real-time quantitative reverse transcription-PCR assay utilized and adapted during the outbreak proved to be highly sensitive and sufficiently robust for field use. Partial marburgvirus RNA sequence analysis revealed up to 21% nucleotide divergence among the previously characterized East African strains, with the most distinct being Ravn from Kenya (1987). The Angolan strain was less different (∼7%) from the main group of East African marburgviruses than one might expect given the large geographic separation. To more precisely analyze the virus genetic differences between outbreaks and among viruses within the Angola outbreak itself, a total of 16 complete virus genomes were determined, including those of the virus isolates Ravn (Kenya, 1987) and 05DRC, 07DRC, and 09DRC (Democratic Republic of Congo, 1998) and the reference Angolan virus isolate (Ang1379v). In addition, complete genome sequences were obtained from RNAs extracted from 10 clinical specimens reflecting various stages of the disease and locations within the Angolan outbreak. While the marburgviruses exhibit high overall genetic diversity (up to 22%), only 6.8% nucleotide difference was found between the West African Angolan viruses and the majority of East African viruses, suggesting that the virus reservoir species in these regions are not substantially distinct. Remarkably few nucleotide differences were found among the Angolan clinical specimens (0 to 0.07%), consistent with an outbreak scenario in which a single (or rare) introduction of virus from the reservoir species into the human population was followed by person-to-person transmission with little accumulation of mutations. This is in contrast to the 1998 to 2000 marburgvirus outbreak, where evidence of several virus genetic lineages (with up to 21% divergence) and multiple virus introductions into the human population was found.

Original languageEnglish (US)
Pages (from-to)6497-6516
Number of pages20
JournalJournal of Virology
Volume80
Issue number13
DOIs
StatePublished - Jul 2006
Externally publishedYes

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Marburgvirus
Angola
Genomics
fever
Disease Outbreaks
Fever
Viruses
genomics
viruses
Centers for Disease Control and Prevention
Western Africa
Nucleotides
Kenya
nucleotides
Centers for Disease Control and Prevention (U.S.)
human population
Marburg Virus Disease
Ebolavirus
Genome
RNA Sequence Analysis

ASJC Scopus subject areas

  • Immunology

Cite this

Towner, J. S., Khristova, M. L., Sealy, T. K., Vincent, M. J., Erickson, B. R., Bawiec, D. A., ... Nichol, S. T. (2006). Marburgvirus genomics and association with a large hemorrhagic fever outbreak in Angola. Journal of Virology, 80(13), 6497-6516. https://doi.org/10.1128/JVI.00069-06

Marburgvirus genomics and association with a large hemorrhagic fever outbreak in Angola. / Towner, Jonathan S.; Khristova, Marina L.; Sealy, Tara K.; Vincent, Martin J.; Erickson, Bobbie R.; Bawiec, Darcy A.; Hartman, Amy L.; Comer, James A.; Zaki, Sherif R.; Ströher, Ute; Gomes Da Silva, Filomena; Del Castillo, Fernando; Rollin, Pierre E.; Ksiazek, Thomas; Nichol, Stuart T.

In: Journal of Virology, Vol. 80, No. 13, 07.2006, p. 6497-6516.

Research output: Contribution to journalArticle

Towner, JS, Khristova, ML, Sealy, TK, Vincent, MJ, Erickson, BR, Bawiec, DA, Hartman, AL, Comer, JA, Zaki, SR, Ströher, U, Gomes Da Silva, F, Del Castillo, F, Rollin, PE, Ksiazek, T & Nichol, ST 2006, 'Marburgvirus genomics and association with a large hemorrhagic fever outbreak in Angola', Journal of Virology, vol. 80, no. 13, pp. 6497-6516. https://doi.org/10.1128/JVI.00069-06
Towner JS, Khristova ML, Sealy TK, Vincent MJ, Erickson BR, Bawiec DA et al. Marburgvirus genomics and association with a large hemorrhagic fever outbreak in Angola. Journal of Virology. 2006 Jul;80(13):6497-6516. https://doi.org/10.1128/JVI.00069-06
Towner, Jonathan S. ; Khristova, Marina L. ; Sealy, Tara K. ; Vincent, Martin J. ; Erickson, Bobbie R. ; Bawiec, Darcy A. ; Hartman, Amy L. ; Comer, James A. ; Zaki, Sherif R. ; Ströher, Ute ; Gomes Da Silva, Filomena ; Del Castillo, Fernando ; Rollin, Pierre E. ; Ksiazek, Thomas ; Nichol, Stuart T. / Marburgvirus genomics and association with a large hemorrhagic fever outbreak in Angola. In: Journal of Virology. 2006 ; Vol. 80, No. 13. pp. 6497-6516.
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