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J Gen Virol 86 (2005), 3327-3336; DOI 10.1099/vir.0.81175-0

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© 2005 Society for General Microbiology

Presence of broadly reactive and group-specific neutralizing epitopes on newly described isolates of Crimean-Congo hemorrhagic fever virus

Asim A. Ahmed1, Jeanne M. McFalls1, Christian Hoffmann1, Claire Marie Filone1, Shaun M. Stewart1, Jason Paragas2, Shabot Khodjaev3, Dilbar Shermukhamedova3, Connie S. Schmaljohn2, Robert W. Doms1 and Andrea Bertolotti-Ciarlet1

1 Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA
2 Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA
3 Institute of Virology, Ministry of Health, Tashkent, Uzbekistan

Correspondence
Andrea Bertolotti-Ciarlet
aciarlet{at}mail.med.upenn.edu

Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the genus Nairovirus of the family Bunyaviridae, causes severe disease in humans with high rates of mortality. The virus has a tripartite genome composed of a small (S), a medium (M) and a large (L) RNA segment; the M segment encodes the two viral glycoproteins, GN and GC. Whilst relatively few full-length M segment sequences are available, it is apparent that both GN and GC may exhibit significant sequence diversity. It is unknown whether considerable antigenic differences exist between divergent CCHFV strains, or whether there are conserved neutralizing epitopes. The M segments derived from viral isolates of a human case of CCHF in South Africa (SPU 41/84), an infected tick (Hyalomma marginatum) in South Africa (SPU 128/81), a human case in Congo (UG 3010), an infected individual in Uzbekistan (U2-2-002) and an infected tick (Hyalomma asiaticum) in China (Hy13) were sequenced fully, and the glycoproteins were expressed. These novel sequences showed high variability in the N-terminal region of GN and more modest differences in the remainder of GN and in GC. Phylogenetic analyses placed these newly identified strains in three of the four previously described M segment groups. Studies with a panel of mAbs specific to GN and GC indicated that there were significant antigenic differences between the M segment groups, although several neutralizing epitopes in both GN and GC were conserved among all strains examined. Thus, the genetic diversity exhibited by CCHFV strains results in significant antigenic differences that will need to be taken into consideration for vaccine development.

The GenBank/EMBL/DDBJ accession numbers for the sequences described in this paper are AY900141–AY900145.

Supplementary figures are available in JGV Online.




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