The high level of amino acid sequence conservation amongst southern African CCHFV isolates implies that this did not result from sequence variation which may result in an inability of T cells to recognise the peptides, but likely represents the HLA diversity within the patient population studied and the differing HLA restrictions of the peptides

The high level of amino acid sequence conservation amongst southern African CCHFV isolates implies that this did not result from sequence variation which may result in an inability of T cells to recognise the peptides, but likely represents the HLA diversity within the patient population studied and the differing HLA restrictions of the peptides. absence of continued antigenic stimulation. T cell depletion studies confirmed that IFN- 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 contamination. Author summary Crimean-Congo haemorrhagic fever virus (CCHFV) is usually a tick-borne virus that causes haemorrhagic fever with fatalities in humans. Clinical disease has been described in Africa, Asia, Eastern Europe, the Middle East, Turkey and more recently Greece, India and Spain. In the absence of specific anti-virals and vaccines, supportive therapy is the method of treatment. Specific T cell epitopes have yet to be identified for CCHFV following infection and although antibody responses are detectable in survivors, antibody production does not always correlate with viral clearance, implying that innate and T cell immunity likely also play an important role. To further understand the role of T lymphocytes in the immune response to CCHFV contamination, we aimed to determine whether memory T cell responses could be identified in survivors of CCHFV contamination and to identify the viral proteins on which the T cell epitopes are 2′-Deoxyguanosine located. T cell responses to CCHFV peptides were detected in this study population up to 13 years after acute CCHFV infection and provides confirmation of long-lived CD8+ T cell responses. The longevity of the responses 2′-Deoxyguanosine points towards memory T cells playing an important role and implies that effective long term protection from contamination may be achieved through 2′-Deoxyguanosine vaccination. Introduction Crimean-Congo haemorrhagic fever virus (CCHFV) is a member of the family and has a tripartite, single-stranded, unfavorable sense RNA genome [1C3]. The three segments are referred to as the large (L), medium (M) and small (S) segments [4]. The L segment encodes the viral RNA dependant RNA polymerase which is responsible for mRNA synthesis and replication of the RNA genome [5]. The M segment encodes a number of non-structural proteins and two structural glycoproteins, GN and GC [6,7]. The structural glycoproteins are responsible for attachment to AKAP10 host cell surface receptors and therefore determine the host range and cell tropism and are also 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, although the role of this activity in CCHFV contamination is not yet clear [8,9]. CCHFV is the only member of the CCHFV serogroup of medical importance. The other members of the group, Hazara virus and Khasan virus, have not been associated with disease in humans [10C12]. CCHFV contamination in humans is associated with haemorrhagic fever and is fatal in up to 30% of cases [13]. The principal vectors of the virus are ticks belonging to the genus [14]. The distribution of disease follows that of the principal vector of the virus [13,15]. Clinical disease is usually well described in Africa, Asia, Eastern Europe and the Middle East and has recently emerged in Turkey, Greece, India and Spain [16C19]. With nearly 10 000 human cases reported to the Ministry of Health in Turkey between 2002 and December 2015, as well as expanding areas of endemicity, the development of effective preventative and therapeutic measures have.