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Abstract
There has been a dramatic increase in the number of insect-specific flaviviruses (ISFs) discovered in the last decade. Historically, these viruses have generated limited interest due to their inability to infect vertebrate cells. This viewpoint has changed in recent years because some ISFs have been shown to enhance or suppress the replication of medically important flaviviruses in co-infected mosquito cells. Additionally, comparative studies between ISFs and medically important flaviviruses can provide a unique perspective as to why some flaviviruses possess the ability to infect and cause devastating disease in humans while others do not. ISFs have been isolated exclusively from mosquitoes in nature but the detection of ISF-like sequences in sandflies and chironomids indicates that they may also infect other dipterans. ISFs can be divided into two distinct phylogenetic groups. The first group currently consists of approximately 12 viruses and includes cell fusing agent virus, Kamiti River virus and Culex flavivirus. These viruses are phylogenetically distinct from all other known flaviviruses. The second group, which is apparently not monophyletic, currently consists of nine viruses and includes Chaoyang virus, Nounané virus and Lammi virus. These viruses phylogenetically affiliate with mosquito/vertebrate flaviviruses despite their apparent insect-restricted phenotype. This article provides a review of the discovery, host range, mode of transmission, superinfection exclusion ability and genomic organization of ISFs. This article also attempts to clarify the ISF nomenclature because some of these viruses have been assigned more than one name due to their simultaneous discoveries by independent research groups.
Highlights
All viruses in the genus Flavivirus possess a single-stranded, positive-senseRNA genome of approximately 11 kb [1]
Cx. quinquefasciatus infected with Culex flavivirus (CxFV) alone but was detected in the saliva of mosquitoes co-infected with CxFV and West Nile virus (WNV) [63]
Experiments performed with field-infected Cx. pipiens revealed that transovarial transmission (TOT) is an efficient mechanism for CxFV persistence [64]
Summary
All viruses in the genus Flavivirus (family Flaviviridae) possess a single-stranded, positive-sense. The genomes of some flaviviruses appear to encode an additional protein as a consequence of ribosomal frameshifting as discussed later in this review. Despite their similar genomic organizations, flaviviruses possess fundamental differences in their host ranges and transmissibilities. Dual-host flaviviruses can be further divided into mosquito/vertebrate and tick/vertebrate viruses. ISFs in the second group phylogenetically affiliate with mosquito/vertebrate flaviviruses and, for the purpose of this review, will be referred to as dual-host affiliated ISFs (dISFs). Species names are colorcoded as follows: cISFs—blue; dISFs—green; NKV flaviviruses—red; mosquito/vertebrate flaviviruses—purple; tick/vertebrate flaviviruses—black
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