title: Presence of broadly reactive and group-specific neutralizing epitopes on newly described isolates of Crimean-Congo hemorrhagic fever virus.
abstract: 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, G(N) and G(C). Whilst relatively few full-length M segment sequences are available, it is apparent that both G(N) and G(C) 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 G(N) and more modest differences in the remainder of G(N) and in G(C). 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 G(N) and G(C) indicated that there were significant antigenic differences between the M segment groups, although several neutralizing epitopes in both G(N) and G(C) 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.
authors.affiliation: Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Asim A
authors.initials: AA
authors.lastname: Ahmed
authors.affiliation: Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: McFalls
authors.affiliation: Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Hoffmann
authors.affiliation: Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Claire Marie
authors.initials: CM
authors.lastname: Filone
authors.affiliation: Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Shaun M
authors.initials: SM
authors.lastname: Stewart
authors.affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Paragas
authors.affiliation: Institute of Virology, Ministry of Health, Tashkent, Uzbekistan.
authors.forename: Shabot
authors.initials: S
authors.lastname: Khodjaev
authors.affiliation: Institute of Virology, Ministry of Health, Tashkent, Uzbekistan.
authors.forename: Dilbar
authors.initials: D
authors.lastname: Shermukhamedova
authors.affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Connie S
authors.initials: CS
authors.lastname: Schmaljohn
authors.affiliation: Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Doms
authors.affiliation: Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bertolotti-Ciarlet
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D003225:Hemorrhagic Fever Virus, Crimean-Congo / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010802:Phylogeny; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D000939:Epitopes; D006023:Glycoproteins; D012367:RNA, Viral; D014764:Viral Proteins