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Viruses
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Biology and Treatment of Tick-Borne Viral Pathogens
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Biology and Treatment of Tick-Borne Viral Pathogens

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (31 May 2018) | Viewed by 58256

Special Issue Editors

Dr. Brian Geiss

E-Mail Website
Guest Editor
Arthropod-Borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA
Interests: flaviviruses; alphaviruses; antiviral drug development; antivirals targeting RNA capping; viral RNA genome replication; diagnostics
Dr. Greg Ebel

E-Mail Website
Guest Editor
Arthropod-Borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA
Interests: flaviviruses; virus–host interactions; virus evolutionary biology; emerging viruses, surveillance

Special Issue Information

Dear Colleagues,  

Tick-borne viruses, such as Powassan, Bourbon, Heartland, and Tick-Borne Encephalitis viruses, cause significant morbidity and mortality every year, but the impact of these important viral pathogens are often overshadowed by their mosquito-borne counterparts. With climate change causing dramatic shifts in the traditional geographic ranges of many tick species and increased interaction of humans with tick ranges, it is expected that tick-borne viral diseases will continue to become more prevalent over the next few decades.  Although some similarities exist between tick-borne viral diseases and related mosquito-borne diseases, the ecology and physiology of ticks is quite distinct from that of mosquitoes, with important implications for the virus-host interaction and the consequent burden of tick-borne viral diseases. 

This Viruses Special Issue will focus on summarizing our current knowledge in the ecology, transmission, pathogenesis, immunity, and treatment of tick-borne viral diseases, providing an essential current overview of the field and helping to define the next stages of investigation into these important human pathogens.

Dr. Brian Geiss
Dr. Greg Ebel
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Tick-borne viruses
  • ecology
  • transmission
  • pathogenesis
  • immunity
  • antivirals
  • therapeutics
  • prevention

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Published Papers (7 papers)

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Research

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19 pages, 4589 KiB  
Article
Co-Infection Patterns in Individual Ixodes scapularis Ticks Reveal Associations between Viral, Eukaryotic and Bacterial Microorganisms
by Shaun T. Cross, Marylee L. Kapuscinski, Jacquelyn Perino, Bernadette L. Maertens, James Weger-Lucarelli, Gregory D. Ebel and Mark D. Stenglein
Viruses 2018, 10(7), 388; https://doi.org/10.3390/v10070388 - 22 Jul 2018
Cited by 44 | Viewed by 8043
Abstract
Ixodes scapularis ticks harbor a variety of microorganisms, including eukaryotes, bacteria and viruses. Some of these can be transmitted to and cause disease in humans and other vertebrates. Others are not pathogenic, but may impact the ability of the tick to harbor and [...] Read more.
Ixodes scapularis ticks harbor a variety of microorganisms, including eukaryotes, bacteria and viruses. Some of these can be transmitted to and cause disease in humans and other vertebrates. Others are not pathogenic, but may impact the ability of the tick to harbor and transmit pathogens. A growing number of studies have examined the influence of bacteria on tick vector competence but the influence of the tick virome remains less clear, despite a surge in the discovery of tick-associated viruses. In this study, we performed shotgun RNA sequencing on 112 individual adult I. scapularis collected in Wisconsin, USA. We characterized the abundance, prevalence and co-infection rates of viruses, bacteria and eukaryotic microorganisms. We identified pairs of tick-infecting microorganisms whose observed co-infection rates were higher or lower than would be expected, or whose RNA levels were positively correlated in co-infected ticks. Many of these co-occurrence and correlation relationships involved two bunyaviruses, South Bay virus and blacklegged tick phlebovirus-1. These viruses were also the most prevalent microorganisms in the ticks we sampled, and had the highest average RNA levels. Evidence of associations between microbes included a positive correlation between RNA levels of South Bay virus and Borrelia burgdorferi, the Lyme disease agent. These findings contribute to the rationale for experimental studies on the impact of viruses on tick biology and vector competence. Full article
(This article belongs to the Special Issue Biology and Treatment of Tick-Borne Viral Pathogens)
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12 pages, 1253 KiB  
Article
Interactions of Human Dermal Dendritic Cells and Langerhans Cells Treated with Hyalomma Tick Saliva with Crimean-Congo Hemorrhagic Fever Virus
by Sergio E. Rodriguez, Alexander J. McAuley, Aysen Gargili and Dennis A. Bente
Viruses 2018, 10(7), 381; https://doi.org/10.3390/v10070381 - 20 Jul 2018
Cited by 15 | Viewed by 4492
Abstract
Crimean-Congo hemorrhagic fever virus is one the most important and wide spread tick-borne viruses. Very little is known about the transmission from the tick and the early aspects of pathogenesis. Here, we generate human cutaneous antigen presenting cells—dermal dendritic cells and Langerhans cells—from [...] Read more.
Crimean-Congo hemorrhagic fever virus is one the most important and wide spread tick-borne viruses. Very little is known about the transmission from the tick and the early aspects of pathogenesis. Here, we generate human cutaneous antigen presenting cells—dermal dendritic cells and Langerhans cells—from umbilical cord progenitor cells. In order to mimic the environment created during tick feeding, tick salivary gland extract was generated from semi-engorged Hyalomma marginatum ticks. Our findings indicate that human dermal dendritic cells and Langerhans cells are susceptible and permissive to Crimean-Congo hemorrhagic fever virus infection, however, to different degrees. Infection leads to cell activation and cytokine/chemokine secretion, although these responses vary between the different cell types. Hyalomma marginatum salivary gland extract had minimal effect on cell responses, with some synergy with viral infection with respect to cytokine secretion. However, salivary gland extract appeared to inhibit antigen presenting cells (APCs) migration. Based on the findings here we hypothesize that human dermal dendritic cells and Langerhans cells serve as early target cells. Rather affecting Crimean-Congo hemorrhagic fever virus replication, tick saliva likely immunomodulates and inhibits migration of these APCs from the feeding site. Full article
(This article belongs to the Special Issue Biology and Treatment of Tick-Borne Viral Pathogens)
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Review

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17 pages, 1148 KiB  
Review
Heartland Virus Epidemiology, Vector Association, and Disease Potential
by Aaron C. Brault, Harry M. Savage, Nisha K. Duggal, Rebecca J. Eisen and J. Erin Staples
Viruses 2018, 10(9), 498; https://doi.org/10.3390/v10090498 - 14 Sep 2018
Cited by 81 | Viewed by 10141
Abstract
First identified in two Missouri farmers exhibiting low white-blood-cell and platelet counts in 2009, Heartland virus (HRTV) is genetically closely related to severe fever with thrombocytopenia syndrome virus (SFTSV), a tick-borne phlebovirus producing similar symptoms in China, Korea, and Japan. Field isolations of [...] Read more.
First identified in two Missouri farmers exhibiting low white-blood-cell and platelet counts in 2009, Heartland virus (HRTV) is genetically closely related to severe fever with thrombocytopenia syndrome virus (SFTSV), a tick-borne phlebovirus producing similar symptoms in China, Korea, and Japan. Field isolations of HRTV from several life stages of unfed, host-seeking Amblyomma americanum, the lone star tick, implicated it as a putative vector capable of transstadial transmission. Laboratory vector competence assessments confirmed transstadial transmission of HRTV, demonstrated vertical infection, and showed co-feeding infection between A. americanum. A vertical infection rate of 33% from adult females to larvae in the laboratory was observed, while only one of 386 pools of molted nymphs (1930) reared from co-feeding larvae was positive for HRTV (maximum-likelihood estimate of infection rate = 0.52/1000). Over 35 human HRTV cases, all within the distribution range of A. americanum, have been documented. Serological testing of wildlife in areas near the index human cases, as well as in widely separated regions of the eastern United States where A. americanum occur, indicated many potential hosts such as raccoons and white-tailed deer. Attempts, however, to experimentally infect mice, rabbits, hamsters, chickens, raccoons, goats, and deer failed to produce detectable viremia. Immune-compromised mice and hamsters are the only susceptible models. Vertical infection augmented by co-feeding transmission could play a role in maintaining the virus in nature. A more complete assessment of the natural transmission cycle of HRTV coupled with serosurveys and enhanced HRTV disease surveillance are needed to better understand transmission dynamics and human health risks. Full article
(This article belongs to the Special Issue Biology and Treatment of Tick-Borne Viral Pathogens)
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11 pages, 2010 KiB  
Review
Tick–Virus–Host Interactions at the Cutaneous Interface: The Nidus of Flavivirus Transmission
by Meghan E. Hermance and Saravanan Thangamani
Viruses 2018, 10(7), 362; https://doi.org/10.3390/v10070362 - 7 Jul 2018
Cited by 29 | Viewed by 5923
Abstract
Tick-borne viral diseases continue to emerge in the United States, as clearly evident from the increase in Powassan encephalitis virus, Heartland virus, and Bourbon virus infections. Tick-borne flaviviruses (TBFVs) are transmitted to the mammalian host along with the infected tick saliva during blood-feeding. [...] Read more.
Tick-borne viral diseases continue to emerge in the United States, as clearly evident from the increase in Powassan encephalitis virus, Heartland virus, and Bourbon virus infections. Tick-borne flaviviruses (TBFVs) are transmitted to the mammalian host along with the infected tick saliva during blood-feeding. Successful tick feeding is facilitated by a complex repertoire of pharmacologically active salivary proteins/factors in tick saliva. These salivary factors create an immunologically privileged micro-environment in the host’s skin that influences virus transmission and pathogenesis. In this review, we will highlight tick determinants of TBFV transmission with a special emphasis on tick–virus–host interactions at the cutaneous interface. Full article
(This article belongs to the Special Issue Biology and Treatment of Tick-Borne Viral Pathogens)
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20 pages, 5673 KiB  
Review
Tick-Borne Encephalitis Virus: A Structural View
by Lauri I. A. Pulkkinen, Sarah J. Butcher and Maria Anastasina
Viruses 2018, 10(7), 350; https://doi.org/10.3390/v10070350 - 28 Jun 2018
Cited by 68 | Viewed by 14652
Abstract
Tick-borne encephalitis virus (TBEV) is a growing health concern. It causes a severe disease that can lead to permanent neurological complications or death and the incidence of TBEV infections is constantly rising. Our understanding of TBEV’s structure lags behind that of other flaviviruses, [...] Read more.
Tick-borne encephalitis virus (TBEV) is a growing health concern. It causes a severe disease that can lead to permanent neurological complications or death and the incidence of TBEV infections is constantly rising. Our understanding of TBEV’s structure lags behind that of other flaviviruses, but has advanced recently with the publication of a high-resolution structure of the TBEV virion. The gaps in our knowledge include: aspects of receptor binding, replication and virus assembly. Furthermore, TBEV has mostly been studied in mammalian systems, even though the virus’ interaction with its tick hosts is a central part of its life cycle. Elucidating these aspects of TBEV biology are crucial for the development of TBEV antivirals, as well as the improvement of diagnostics. In this review, we summarise the current structural knowledge on TBEV, bringing attention to the current gaps in our understanding, and propose further research that is needed to truly understand the structural-functional relationship of the virus and its hosts. Full article
(This article belongs to the Special Issue Biology and Treatment of Tick-Borne Viral Pathogens)
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21 pages, 9528 KiB  
Review
Tick-Borne Flaviviruses and the Type I Interferon Response
by Richard Lindqvist, Arunkumar Upadhyay and Anna K. Överby
Viruses 2018, 10(7), 340; https://doi.org/10.3390/v10070340 - 21 Jun 2018
Cited by 29 | Viewed by 8377
Abstract
Flaviviruses are globally distributed pathogens causing millions of human infections every year. Flaviviruses are arthropod-borne viruses and are mainly transmitted by either ticks or mosquitoes. Mosquito-borne flaviviruses and their interactions with the innate immune response have been well-studied and reviewed extensively, thus this [...] Read more.
Flaviviruses are globally distributed pathogens causing millions of human infections every year. Flaviviruses are arthropod-borne viruses and are mainly transmitted by either ticks or mosquitoes. Mosquito-borne flaviviruses and their interactions with the innate immune response have been well-studied and reviewed extensively, thus this review will discuss tick-borne flaviviruses and their interactions with the host innate immune response. Full article
(This article belongs to the Special Issue Biology and Treatment of Tick-Borne Viral Pathogens)
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18 pages, 1070 KiB  
Review
Viral Determinants of Virulence in Tick-Borne Flaviviruses
by Eliza M. Kellman, Danielle K. Offerdahl, Wessam Melik and Marshall E. Bloom
Viruses 2018, 10(6), 329; https://doi.org/10.3390/v10060329 - 16 Jun 2018
Cited by 33 | Viewed by 5595
Abstract
Tick-borne flaviviruses have a global distribution and cause significant human disease, including encephalitis and hemorrhagic fever, and often result in neurologic sequelae. There are two distinct properties that determine the neuropathogenesis of a virus. The ability to invade the central nervous system (CNS) [...] Read more.
Tick-borne flaviviruses have a global distribution and cause significant human disease, including encephalitis and hemorrhagic fever, and often result in neurologic sequelae. There are two distinct properties that determine the neuropathogenesis of a virus. The ability to invade the central nervous system (CNS) is referred to as the neuroinvasiveness of the agent, while the ability to infect and damage cells within the CNS is referred to as its neurovirulence. Examination of laboratory variants, cDNA clones, natural isolates with varying pathogenicity, and virally encoded immune evasion strategies have contributed extensively to our understanding of these properties. Here we will review the major viral determinants of virulence that contribute to pathogenesis and influence both neuroinvasiveness and neurovirulence properties of tick-borne flaviviruses, focusing particularly on the envelope protein (E), nonstructural protein 5 (NS5), and the 3′ untranslated region (UTR). Full article
(This article belongs to the Special Issue Biology and Treatment of Tick-Borne Viral Pathogens)
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