Survival dynamics of tick-borne encephalitis virus in Ixodes ricinus ticks

Slovák, Mirko; Kazimírová, Mária; Siebenstichová, Marta; Ustaníková, Katarína; Klempa, Boris; Грицун, Т.С.; Gould, Ernest A.; Nuttall, Patricia A.

doi:10.1016/j.ttbdis.2014.07.019

Cited by 43 publications

(37 citation statements)

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“…Unfed female tick organs were utilized for this study (as in the study by Sunyakumthorn et al [78]); thus, results may reflect a bias to a specific adult tick sex (or tick life stage) and physiological state. In vivo studies with TBEV in Ixodes ricinus ticks have shown higher levels of TBEV replication in blood-fed versus unfed ticks and, in particular, greater replication in salivary glands (60). We hypothesize that a similar trend may occur with TBFV replication in ex vivo organs from blood-fed versus unfed I. scapularis ticks; thus, use of organs from blood-fed ticks may be an option for future studies.…”

Section: Discussionmentioning

confidence: 83%

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Flavivirus Infection ofIxodes scapularis(Black-Legged Tick)Ex VivoOrganotypic Cultures and Applications for Disease Control

Grabowski¹,

Tsetsarkin

Long³

et al. 2017

mBio

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Ixodes scapularis ticks transmit many infectious agents that cause disease, including tick-borne flaviviruses (TBFVs). TBFV infections cause thousands of human encephalitis cases worldwide annually. In the United States, human TBFV infections with Powassan virus (POWV) are increasing and have a fatality rate of 10 to 30%. Additionally, Langat virus (LGTV) is a TBFV of low neurovirulence and is used as a model TBFV. TBFV replication and dissemination within I. scapularis organs are poorly characterized, and a deeper understanding of virus biology in this vector may inform effective countermeasures to reduce TBFV transmission. Here, we describe short-term, I. scapularis organ culture models of TBFV infection. Ex vivo organs were metabolically active for 9 to 10 days and were permissive to LGTV and POWV replication. Imaging and videography demonstrated replication and spread of green fluorescent protein-expressing LGTV in the organs. Immunohistochemical staining confirmed LGTV envelope and POWV protein synthesis within the infected organs.LGTV-and POWV-infected organs produced infectious LGTV and POWV; thus, the ex vivo cultures were suitable for study of virus replication in individual organs. LGTVand POWV-infected midgut and salivary glands were subjected to double-stranded RNA (dsRNA) transfection with dsRNA to the LGTV 3= untranslated region (UTR), which reduced infectious LGTV and POWV replication, providing a proof-of-concept use of RNA interference in I. scapularis organ cultures to study the effects on TBFV replication. The results contribute important information on TBFV localization within ex vivo I. scapularis organs and provide a significant translational tool for evaluating recombinant, live vaccine candidates and potential tick transcripts and proteins for possible therapeutic use and vaccine development to reduce TBFV transmission.IMPORTANCE Tick-borne flavivirus (TBFV) infections cause neurological and/or hemorrhagic disease in humans worldwide. There are currently no licensed therapeutics or vaccines against Powassan virus (POWV), the only TBFV known to circulate in North America. Evaluating tick vector targets for antitick vaccines directed at reducing TBFV infection within the arthropod vector is a critical step in identifying efficient approaches to controlling TBFV transmission. This study characterized infection of female Ixodes scapularis tick organ cultures of midgut, salivary glands, and synganglion with the low-neurovirulence Langat virus (LGTV) and the more pathogenic POWV. Cell types of specific organs were susceptible to TBFV infection, and a difference in LGTV and POWV replication was noted in TBFV-infected organs. This tick organ culture model of TBFV infection will be useful for various applications,

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Section: Discussionmentioning

confidence: 83%

“…ticks (30,60,61). Infectious LGTV and POWV were produced from all three infected tick organ cultures ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Flavivirus Infection ofIxodes scapularis(Black-Legged Tick)Ex VivoOrganotypic Cultures and Applications for Disease Control

Grabowski¹,

Tsetsarkin

Long³

et al. 2017

mBio

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“…While TBEV can be maintained in tick-populations by trans-stadial and trans-ovarial transmission [71], horizontal transmission via co-feeding of ticks on small mammals may also play a significant role in maintaining the virus in ticks [72]. In support of co-feeding transmission, recent studies with Powassan virus (POWV) have shown that a potential mammalian host for POWV, Peromyscus leucopus , did not develop disease when infected with POWV and did not develop a sufficient viremia to directly infect feeding ticks [73].…”

Section: Origins Of Flavivirus Researchmentioning

confidence: 99%

Historical Perspectives on Flavivirus Research

Holbrook¹

2017

Viruses

135

104

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The flaviviruses are small single-stranded RNA viruses that are typically transmitted by mosquito or tick vectors. These “arboviruses” are found around the world and account for a significant number of cases of human disease. The flaviviruses cause diseases ranging from mild or sub-clinical infections to lethal hemorrhagic fever or encephalitis. In many cases, survivors of neurologic flavivirus infections suffer long-term debilitating sequelae. Much like the emergence of West Nile virus in the United States in 1999, the recent emergence of Zika virus in the Americas has significantly increased the awareness of mosquito-borne viruses. The diseases caused by several flaviviruses have been recognized for decades, if not centuries. However, there is still a lot that is unknown about the flaviviruses as the recent experience with Zika virus has taught us. The objective of this review is to provide a general overview and some historical perspective on several flaviviruses that cause significant human disease. In addition, available medical countermeasures and significant gaps in our understanding of flavivirus biology are also discussed.

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“…Similarly, successful transmission of POWV is likely to occur within 15 min of I. scapularis attachment (Ebel and Kramer, 2004), and transmission of Thogoto virus (THOV) within 24 h of attachment of R. appendiculatus (Kaufman and Nuttall, 2003). Onset of feeding was found to enhance amplification of TBEV in SG of I. persulcatus and I. ricinus (Alekseev and Chunikhin, 1990b; Khasnatinov et al, 2009; Slovák et al, 2014a) and of THOV in SG of R. appendiculatus (Kaufman and Nuttall, 2003). However, knowledge on the critical stages of TBV survival in their vectors is limited (Nuttall, 2014; Slovák et al, 2014a).…”

Section: Ticks As Vectors Of Virusesmentioning

confidence: 99%

Tick-Borne Viruses and Biological Processes at the Tick-Host-Virus Interface

Kazimírová

Thangamani

Bartíková

et al. 2017

Front. Cell. Infect. Microbiol.

Self Cite

106

103

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Ticks are efficient vectors of arboviruses, although less than 10% of tick species are known to be virus vectors. Most tick-borne viruses (TBV) are RNA viruses some of which cause serious diseases in humans and animals world-wide. Several TBV impacting human or domesticated animal health have been found to emerge or re-emerge recently. In order to survive in nature, TBV must infect and replicate in both vertebrate and tick cells, representing very different physiological environments. Information on molecular mechanisms that allow TBV to switch between infecting and replicating in tick and vertebrate cells is scarce. In general, ticks succeed in completing their blood meal thanks to a plethora of biologically active molecules in their saliva that counteract and modulate different arms of the host defense responses (haemostasis, inflammation, innate and acquired immunity, and wound healing). The transmission of TBV occurs primarily during tick feeding and is a complex process, known to be promoted by tick saliva constituents. However, the underlying molecular mechanisms of TBV transmission are poorly understood. Immunomodulatory properties of tick saliva helping overcome the first line of defense to injury and early interactions at the tick-host skin interface appear to be essential in successful TBV transmission and infection of susceptible vertebrate hosts. The local host skin site of tick attachment, modulated by tick saliva, is an important focus of virus replication. Immunomodulation of the tick attachment site also promotes co-feeding transmission of viruses from infected to non-infected ticks in the absence of host viraemia (non-viraemic transmission). Future research should be aimed at identification of the key tick salivary molecules promoting virus transmission, and a molecular description of tick-host-virus interactions and of tick-mediated skin immunomodulation. Such insights will enable the rationale design of anti-tick vaccines that protect against disease caused by tick-borne viruses.

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Survival dynamics of tick-borne encephalitis virus in Ixodes ricinus ticks

Cited by 43 publications

References 36 publications

Flavivirus Infection ofIxodes scapularis(Black-Legged Tick)Ex VivoOrganotypic Cultures and Applications for Disease Control

Flavivirus Infection ofIxodes scapularis(Black-Legged Tick)Ex VivoOrganotypic Cultures and Applications for Disease Control

Historical Perspectives on Flavivirus Research

Tick-Borne Viruses and Biological Processes at the Tick-Host-Virus Interface

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