Crimean–Congo Hemorrhagic Fever Virus Past Infections Are Associated with Two Innate Immune Response Candidate Genes in Dromedaries
, Jan Futas 3,4, Martin Plasil 3,4, Tom Loney 5, Pia Weidinger 6, Jeremy V. Camp 6,7, Jolanta Kolodziejek 6, Dafalla O. Kannan 8, Petr Horin 3,4, Norbert Nowotny 5,6 and Pamela A. Burger 1,*Round 1
Reviewer 1 Report
The authors have addressed my previous comments as requested. Thank you.
Reviewer 2 Report
It seems they try best to answer the questions and concerns. I support to accept this manuscript at the present form. Thank you!
Reviewer 3 Report
Camelids have been identified as reservoirs for several zoonotic agents and serve as the primary reservoir of Crimean-Congo hemorrhagic fever virus (CCHFV) in some endemic foci of the UAE and Oman.
Spillover into humans occurs through tick bites or exposure to tissues from infected animals and human-to-human transmission of CCHFV occurs in nosocomial settings. CCHFV infection in humans can lead to severe and often fatal hemorrhagic fever.
The authors here accessed pre-existing dromedaries’ samples and performed genotyping studies specifically targeting immune genes using the samples from dromedaries that tested positive for CCHFV antibodies. Genetic variability is here reported through the investigation of SNPs in gene variants are here reported. The goal was to identify in dromedaries’ genes underlying host defense mechanisms against CCHFV. 114 dromedaries grouped into 83 cases (CCHFV Abs-positive) and 31 controls (CCHFV Abs-negative) were analyzed for 2929 SNPs genotyped in target genes. The authors report finding seven top candidate SNPs located within two genes on chromosomes 9 and 34 in regions coding for FCAR (Immunoglobulin Alpha Fc Receptor on chr9) and CLEC2B (C-type lectin 230 domain family 2 member B on chr34). The authors try to make a link with a potential susceptibility with variations in a gene involved in NK cells stimulation and a gene involved in the Fc receptor function of IgAs potentially impacting phagocytosis, antibody-dependent cell-mediated cytotoxicity, and stimulation of the release of inflammatory mediators. The findings pave the way for more functional pathway analyses as it is crucial to understand the effective response to CCHFV vaccines in camels/dromedaries and potentially inform the immune response to CCHFV in humans.
The reviewer found the research of great interest, the manuscript very well written, and strongly recommends publication of the findings, seeing no further needed revisions.
