Potential Mechanisms of Transmission of Tick-Borne Viruses at the Virus-Tick Interface

Abstract

Ticks (Acari; Ixodidae) are the second most important vector for transmission of pathogens to humans, livestock, and wildlife. Ticks as vectors for viruses have been reported many times over the last 100 years. Tick-borne viruses (TBVs) belong to two orders (Bunyavirales and Mononegavirales) containing nine families (Bunyaviridae, Rhabdoviridae, Asfarviridae, Orthomyxovirida, Reoviridae, Flaviviridae, Phenuviridae, Nyamiviridae, and Nairoviridae). Among these TBVs, some are very pathogenic, causing huge mortality, and hence, deserve to be covered under the umbrella of one health. About 38 viral species are being transmitted by <10% of the tick species of the families Ixodidae and Argasidae. All TBVs are RNA viruses except for the African swine fever virus from the family Asfarviridae. Tick-borne viral diseases have also been classified as an emerging threat to public health and animals, especially in resource-poor communities of the developing world. Tick-host interaction plays an important role in the successful transmission of pathogens. The ticks' salivary glands are the main cellular machinery involved in the uptake, settlement, and multiplication of viruses, which are required for successful transmission into the final host. Furthermore, tick saliva also participates as an augmenting tool during the physiological process of transmission. Tick saliva is an important key element in the successful transmission of pathogens and contains different antimicrobial proteins, e.g., defensin, serine, proteases, and cement protein, which are key players in tick-virus interaction. While tick-virus interaction is a crucial factor in the propagation of tick-borne viral diseases, other factors (physiological, immunological, and gut flora) are also involved. Some immunological factors, e.g., toll-like receptors, scavenger receptors, Janus-kinase (JAK-STAT) pathway, and immunodeficiency (IMD) pathway are involved in tick-virus interaction by helping in virus assembly and acting to increase transmission. Ticks also harbor some endogenous viruses as internal microbial faunas, which also play a significant role in tick-virus interaction. Studies focusing on tick saliva and its role in pathogen transmission, tick feeding, and control of ticks using functional genomics all point toward solutions to this emerging threat. Information regarding tick-virus interaction is somewhat lacking; however, this information is necessary for a complete understanding of transmission TBVs and their persistence in nature. This review encompasses insight into the ecology and vectorial capacity of tick vectors, as well as our current understanding of the predisposing, enabling, precipitating, and reinforcing factors that influence TBV epidemics. The review explores the cellular, biochemical, and immunological tools which ensure and augment successful evading of the ticks' defense systems and transmission of the viruses to the final hosts at the virus-vector interface. The role of functional genomics, proteomics, and metabolomics in profiling tick-virus interaction is also discussed. This review is an initial attempt to comprehensively elaborate on the epidemiological determinants of TBVs with a focus on intra-vector physiological processes involved in the successful execution of the docking, uptake, settlement, replication, and transmission processes of arboviruses. This adds valuable data to the existing bank of knowledge for global stakeholders, policymakers, and the scientific community working to devise appropriate strategies to control ticks and TBVs.

Discovery of the Role of Tick Salivary Glands in Enhancement of Virus Transmission—Beginning of an Exciting Story

“…SAT factors promoting virus transmission have gained attention again since the 2010s, which has been reflected in increasing numbers of papers published on this topic. In a few review papers, knowledge on the known effects of tick saliva on transmission of tick-borne viruses has been updated [ 20 , 24 , 25 , 26 ]. However, no particular salivary molecules directly involved in enhancing/assisting virus transmission have been identified to date.…”

Distribution pattern of Crimean–Congo Hemorrhagic Fever in Asia and the Middle East

“…Tick-borne viruses belong to the Bunyavirales and Mononegavirales orders. These orders contain nine families that cause tick-borne diseases ( 10 ). Southeast Asian countries are more vulnerable because of the increasing population and the developing nature of healthcare infrastructure and communities.…”

The tick saliva peptide HIDfsin2 promotes the tick-borne virus SFTSV replication in vitro by enhancing p38 signal pathway

“…Tick–host interaction is crucial for pathogen transmission. Tick salivary gland is an important site for virus uptake and reproduction, and the complex components of the salivary gland play a key role in virus transmission (Kazimírová et al 2017 ; Maqbool et al 2022 ). Studies had reported that protein or peptide mixtures in salivary gland enhance virus transmission through host immune regulation rather than through direct influence on virus (Jones et al 1989 , 1990 ).…”