The possible role of CCR5Δ32 mutation in Crimean‐Congo hemorrhagic fever infection

Abstract

Crimean-Congo hemorrhagic fever infection (CCHF) is a viral zoonosis. The pathogenesis of this disease has not been established so far, however, cytokines account for its progression and outcome. The aim of the present study is to investigate the association between chemokine receptor 5 (CCR5) gene Δ32 mutation and pathogenity, severity, and mortality of CCHF. This case-control study included 133 CCHF patients diagnosed by detection of CCHV RNA positivity and 97 healthy control subjects. CCR5 gene Δ32 mutation analyzed by polymerase chain reaction (PCR) method. The results were compared by using SPSS 16.0 and WINPEPI software's. The genotype distribution and allele frequency of the CCR5Δ32 were statistically different between the patients and the control group (P = 0.017; OR: 4.98 95% CI = 1.65-14.99 and P = 0.019; OR:4.76 95%CI = 1.30-17.50, respectively). CCR5/CCR5 (W/W) genotype and W allele of CCR5 gene were more common in patient group than in controls. There was no significant difference in severe and mild cases with regard to genotype distribution and allele distribution of CCR5Δ32 mutation (P >0.05). These results suggest that the CCR5 gene and its product might play a role in the pathogenesis of CCHF disease. Future studies will help us to uncover the exact role of CCR5 in the pathogenesis and prognosis of CCHF and to treat the disease.

Beyond HIV infection: Neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases

“…However, further studies are needed to explain the mechanisms by which CCR5 participates in CCHFV infection. In the same study, the CCR5Δ32 was not significantly associated with disease severity, clinical parameters, or mortality rate (Rustemoglu et al, 2017). Together, these findings (Table 6) indicate that the effect of CCR5Δ32 is given specifically on resistance against CCHFV infection, without affecting the pathogenesis/outcome of Crimean-Congo hemorrhagic fever.…”

“…Engin et al (2009) evaluated the CCR5Δ32 in 15 Turkish CCHFVinfected individuals and observed the wild-type homozygous genotype in all cases. In a subsequent study evaluating the Turkish population, Rustemoglu et al (2017) found a protective effect of CCR5Δ32 heterozygous genotype and Δ32 allele on CCHFV infection, since the genotype and allele frequencies were higher in controls than in CCHFVinfected individuals. Conversely, the wild-type genotype (normal CCR5 expression) was prevalent among infected individuals.…”

The Expanding Therapeutic Perspective of CCR5 Blockade

“…CCR5 may instead be detrimental in patients with cerebral malaria, in brain samples of whom it was found to be upregulated ( 26 ). The CCR5Δ32 allele seems to be associated with resistance to Crimean-Congo hemorrhagic fever (CCHF) virus infection, at least in the Turkish population ( 27 ). Indeed, CCL3, CCL4, and CCL5, natural ligands of CCR5, are associated with CCHF, and their levels are increased in adult patients with the infection ( 28 ).…”

Predominance of the heterozygous CCR5 delta‐24 deletion in African individuals resistant to HIV infection might be related to a defect in CCR5 addressing at the cell surface

“…Similarly, we might assume that hCCR5Δ24 may have been selected in Africa by other infectious diseases. The homozygous wtCCR5 individuals are indeed more common in Crimean‐Congo haemorrhagic fever infected patients and CCR5 knock‐out mice are resistant to lethal Dengue virus infection . In this regard, the putative East African localization of the hCCR5Δ24 is remarkable.…”