Abstract
In 2019, the World Health Organization declared 3 billion to be at risk of developing Crimean Congo Hemorrhagic Fever (CCHF). The causative agent of this deadly infection is CCHFV. The data related to the biology and immunology of CCHFV are rather scarce. Due to its indispensable roles in the viral life cycle, NP becomes a logical target for detailed viral immunology studies. In this study, humoral immunity to NP was investigated in CCHF survivors, as well as in immunized mice and rabbits. Abundant antibody response against NP was demonstrated both during natural infection in humans and following experimental immunizations in mice and rabbits. Also, cellular immune responses to recombinant NP (rNP) was detected in multispecies. This study represents the most comprehensive investigation on NP as an inducer of both humoral and cellular immunity in multiple hosts and proves that rNP is an excellent candidate warranting further immunological studies specifically on vaccine investigations.
Highlights
Crimean Congo Hemorrhagic Fever Virus is a tick-borne virus belonging to the Orthonairovius genus of the Nairoviridae family with a tri-segmented genome consisting of small (S), medium (M), and large (L) segments encoding nucleocapsid protein (NP), glycoprotein precursor (GPC) and an RNA-dependent RNA polymerase (RdRp), respectively
The expression of Crimean Congo Hemorrhagic Fever Virus (CCHFV) recombinant NP (rNP) in E. coli showed that, even though the substantial amount of protein production achieved, expressed proteins accumulated as inclusion bodies
The native structure of the rNP has been confirmed with CCHFV antibody positive human sera in an Enzyme immunoassay (EIA) assay and this rNP reacted with IgG generated to viral NP
Summary
Crimean Congo Hemorrhagic Fever Virus is a tick-borne virus belonging to the Orthonairovius genus of the Nairoviridae family with a tri-segmented genome consisting of small (S), medium (M), and large (L) segments encoding nucleocapsid protein (NP), glycoprotein precursor (GPC) and an RNA-dependent RNA polymerase (RdRp), respectively. CCHFV encodes nonstructural protein NSs from the S segment in an ambisense orientation and the other nonstructural protein NSm from the M segment after posttranslational cleavage of GPC. Other proteins such as GP38, GP85, GP160, and a mucin-like domain (MLD) are produced during this cleavage [1]. CCHFV has a wide geographical distribution with continued expansion, causing asymptomatic infections or disease generally with mild flu-like to moderate symptoms [2,3]. The disease can progress to a life-threatening phase resulting in hemorrhages, disseminated intravascular coagulation, multiple organ failure, and shock [4,5]. Community-acquired, and nosocomial infections are reported [1,6,7,8]
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