Influence of laboratory animal hosts on the life cycle of Hyalomma marginatum and implications for an in vivo transmission model for Crimean-Congo hemorrhagic fever virus

Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is one of the most geographically widespread arboviruses and causes a severe hemorrhagic syndrome in humans. The virus circulates in nature in a vertebrate-tick cycle and ticks of the genus Hyalomma are the main vectors and reservoirs. Although the tick vector plays a central role in the maintenance and transmission of CCHFV in nature, comparatively little is known of CCHFV-tick interactions. This is mostly due to the fact that establishing tick colonies is laborious, and working with CCHFV requires a biosafety level 4 laboratory (BSL4) in many countries. Nonetheless, an in vivo transmission model is essential to understand the epidemiology of the transmission cycle of CCHFV. In addition, important parameters such as vectorial capacity of tick species, levels of infection in the host necessary to infect the tick, and aspects of virus transmission by tick bite including the influence of tick saliva, cannot be investigated any other way. Here, we evaluate the influence of different laboratory animal species as hosts supporting the life cycle of Hyalomma marginatum, a two-host tick. Rabbits were considered the host of choice for the maintenance of the uninfected colonies due to high larval attachment rates, shorter larval-nymphal feeding times, higher nymphal molting rates, high egg hatching rates, and higher conversion efficiency index (CEI). Furthermore, we describe the successful establishment of an in vivo transmission model for CCHFV in a BSL4 biocontainment setting using interferon knockout mice. This will give us a new tool to study the transmission and interaction of CCHFV with its tick vector.

The role of ticks in the maintenance and transmission of Crimean-Congo hemorrhagic fever virus: A review of published field and laboratory studies

“…Few studies have investigated CCHFV mutation and evolution during its replication in ticks (Dohm et al, 1996; Dickson and Turell, 1992; Gargili et al, 2013; Xia et al, 2016), skewing our current understanding of evolutionary pressure towards the influence of the vertebrate host. Furthermore, the “original” viral sequence when isolated from a tick is often not known as most CCHFV isolates studied in the laboratory have been generated by multiple mouse-brain passage or mammalian cell culture.…”

“…This might indicate that viral replication is stimulated by attachment and feeding. Gargili et al (2013) fed adult H. marginatum ticks on STAT-1 KO mice challenged with 100 PFU of CCHFV IbAr 10200 and removed them 3 days post virus challenge. Ticks were dissected, RNA extracted from salivary glands, midgut and ovaries, and the extracts tested for CCHFV by RT-qPCR.…”

A chronological review of experimental infection studies of the role of wild animals and livestock in the maintenance and transmission of Crimean-Congo hemorrhagic fever virus

“…Our current knowledge of CCHFV epidemiology has many gaps. The resolution of these gaps needs intensive laboratory work in high-security biosafety conditions, and may be limited by existing transmission model systems (98). Importantly, animal contact has been a direct transmission source of CCHFV to humans.…”

An Emerging Threat of Crimean Congo Hemorrhagic Fever: Call for Preparedness

“…The causative virus has been isolated from all these animals as well as virus specific antibodies have been demonstrated in sera, without any clinical disease. Ixodid (hard ticks) or Argasid (soft ticks) can play role in transmission of the disease (Heyman et al, 2010;Leblebicioglu et al, 2012;Gargili et al, 2013). The principal vector of CCHFV comprises of the ticks of genus Hyalomma (H. marginatum marginatum), probably because both immature and adult stages actively seek hosts for the blood meals, which is required for maturation but the non Hyalomma tick species can also transmit the virus to humans.…”

“…Antibodies have been reported in horses, donkeys, pigs, rhinoceroses, giraffes and buffalo (CFSPH, 2007). Infestation of the immature stages of the ticks by small animals such as rabbits, hares, hedgehogs and rodents assist the maintenance of the virus in the lifecycle of the ticks (Gonzalez et al, 1992;Gargili et al, 2013). Feeding on the ground-dwelling birds, hares and hedgehogs drives larval and nymphal ticks to become infected with CCHFV, (Gale et al, 2010), while the adult ticks become infected while feeding on infected sheep, goats, cattle and pigs (Gale et al, 2010).…”