Recent advances in understanding Crimean-Congo hemorrhagic fever virus

Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is a widely distributed hemorrhagic fever virus and the cause of hemorrhagic disease in Africa, Southern and Eastern Europe, the Middle East, India and Asia. Recent emergence of CCHFV into Spain indicates that the geographic range of this virus is expanding and the presence of its tick vector in several countries without reported disease suggest that CCHFV will continue to spread. Research into CCHFV was historically limited by a lack of suitable animal models and tools to study viral pathogenesis. However, in the past few years the toolset for studying CCHFV has expanded with small animal and non-human primate models for CCHFV being developed along with a reverse genetics system that allows for investigation of viral determinants of disease. These tools have been utilized to understand how CCHFV antagonizes host restriction factors and to develop novel vaccine candidates that may help limit the substantial morbidity and mortality in humans caused by CCHFV.

Keywords: CCHF disease; CCHFV; Crimean-Congo hemorrhagic fever virus; animal models; antivirals; pathogenesis; vaccines.

Figure 1.. Crimean–Congo hemorrhagic fever virus (CCHFV).

The natural reservoir and vector for CCHFV are ticks of the Hyalomma genus. Ticks can become infected at any life-cycle stage during feeding on a viremic animal or during co-feeding with an infected tick, and mammals likely act as important amplification hosts for the virus. Humans are at risk of CCHFV infection from tick bites, animal husbandry, and butchering of infected livestock and during the care of patients with CCHF. In humans, CCHF first presents as a non-specific febrile illness with a sudden onset of fever, headache, myalgia, and nausea. The disease can rapidly progress to the hemorrhagic phase of disease, during which patients exhibit petechiae, hematomas/ecchymosis, and hemorrhages from various sites around the body. Risk factors for death include elevated inflammatory cytokines and liver enzymes, high viral loads, decreased platelets, and absent antibody responses.