Abstract
Crimean-Congo haemorrhagic fever virus (CCHFV) is a member of the Orthonairovirus genus of the Nairoviridae family and is associated with haemorrhagic fever in humans. Although T lymphocyte responses are known to play a role in protection from and clearance of viral infections, specific T cell epitopes have yet to be identified for CCHFV following infection. A panel of overlapping peptides covering the CCHFV nucleoprotein and the structural glycoproteins, GN and GC, were screened by ELISpot assay to detect interferon gamma (IFN-γ) production in vitro by peripheral blood mononuclear cells from eleven survivors with previous laboratory confirmed CCHFV infection. Reactive peptides were located predominantly on the nucleoprotein, with only one survivor reacting to two peptides from the glycoprotein GC. No single epitope was immunodominant, however all but one survivor showed reactivity to at least one T cell epitope. The responses were present at high frequency and detectable several years after the acute infection despite the absence of continued antigenic stimulation. T cell depletion studies confirmed that IFN-γ production as detected using the ELISpot assay was mediated chiefly by CD8+ T cells. This is the first description of CD8+ T cell epitopic regions for CCHFV and provides confirmation of long-lived T cell responses in survivors of CCHFV infection.
Highlights
Crimean-Congo haemorrhagic fever virus (CCHFV) is a member of the Nairoviridae family and has a tripartite, single-stranded, negative sense RNA genome [1,2,3]
Specific T cell epitopes have yet to be identified for CCHFV following infection and antibody responses are detectable in survivors, antibody production does not always correlate with viral clearance, implying that innate and T cell immunity likely play an important role
Eleven survivors were included in the study, all of whom were Caucasian males residing in the Free State and North West provinces of South Africa at the time of CCHFV infection
Summary
Crimean-Congo haemorrhagic fever virus (CCHFV) is a member of the Nairoviridae family and has a tripartite, single-stranded, negative sense RNA genome [1,2,3]. The L segment encodes the viral RNA dependant RNA polymerase which is responsible for mRNA synthesis and replication of the RNA genome [5]. The structural glycoproteins are responsible for attachment to host cell surface receptors and determine the host range and cell tropism and are the targets for neutralizing antibodies. The viral nucleoprotein, encoded by the S segment, binds the RNA segments for the formation of ribonucleoprotein complexes and shows endonuclease activity, the role of this activity in CCHFV infection is not yet clear [8,9]
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