Arboviruses: Variations on an Ancient Theme

Abstract

Arboviruses utilize different strategies to complete their transmission cycle between vertebrate and invertebrate hosts. Most possess an RNA genome coupled with an RNA polymerase lacking proofreading activity and generate large populations of genetically distinct variants, permitting rapid adaptation to environmental changes. With mutation rates of between 10 -6 and 10 -4 substitutions per nucleotide, arboviral genomes rapidly acquire mutations that can lead to viral emergence. Arboviruses can be described in seven families, four of which have medical importance: Togaviridae, Flaviviridae, Bunyaviridae and Reoviridae. The Togaviridae and Flaviviridae both have ssRNA genomes, while the Bunyaviridae and Reoviridae possess segmented RNA genomes. Recent epidemics caused by these arboviruses have been associated with specific mutations leading to enhanced host ranges, vector shifts and virulence. KEYWORDS Arboviruses: the role of RNA genomes in viral adaptation & emergenceThe recent emergence of many arboviruses (i.e., West Nile virus [WNV] in North America [1] and Chikungunya virus [CHIKV] in the Indian Ocean islands [2]) serves as a reminder that these viruses are capable of rapidly adapting to changes in their environment. Such viral epidemics can often be associated with the accumulation of one or more specific mutations in the viral genome and highlight a hallmark feature of arboviruses [3][4][5][6]. Indeed, arboviruses, and many other RNA viruses, employ a unique feature of their RNA-dependent RNA polymerases in order to achieve this rapid adaptation: inaccuracy due to a lack of proofreading activity [7][8][9]. This inaccuracy is the result of evolutionary pressure related to the fidelity of the polymerase. Mutations that decrease the fidelity of viral polymerases, have been shown to cause the accumulation of attenuating and lethal mutations [10], while mutations that enhance the fidelity of the polymerase are also associated with attenuation due to a reduction in the number of viral quasispecies, leaving the virus unable to cope with sudden environmental changes within the host [11]. These studies and others have shown that RNA virus replication balances on a 'knife's edge', with slight changes in their fidelity leading to population collapse [12]. Arboviruses are further constrained by the need to replicate in both a vector and a host species. These two very dissimilar organisms each place unique selective pressures on the arboviral genome, such that mutations that adapt the virus to favor one host are often deleterious in the other host [13][14][15]. Despite this evolutionary pressure, many arboviruses have expanded both their geographical distribution and host range through the generation and accumulation of beneficial mutations [16,17].The major source of these mutations comes from errors that occur during genome replication. Mutation rates during viral RNA replication are in the range of 10 -6 -10 -4 substitutions per For reprint orders, please contact: reprints@futuremedicine.com

Genetics of War and Truce between Mosquitos and Emerging Viruses

“…can transmit and Anopheles have also been implicated as potential vectors (Jupille et al, 2014). In humans, RVFV causes febrile illness in most symptomatic cases but can also result in encephalitis, hemorrhage, and death; of particular concern is the observation that RVFV additionally spreads through aerosols generated by infected animals (e.g., livestock) (Jupille et al, 2014). RVFV encodes three negativesense, single-stranded RNA segments (approximately 12 kb) that produce seven proteins.…”

“…RVFV encodes three negativesense, single-stranded RNA segments (approximately 12 kb) that produce seven proteins. The segmented nature of the genome allows for reassortment events when coinfected with genetic variants (Jupille et al, 2014). First isolated in Kenya in 1931, RVFV has spread to much of the African continent and caused an outbreak in the Arabian Peninsula in 2000.…”