A Newly Isolated Reovirus Has the Simplest Genomic and Structural Organization of Any Reovirus

Abstract

A total of 2,691 mosquitoes representing 17 species was collected from eight locations in southwest Cameroon and screened for pathogenic viruses. Ten isolates of a novel reovirus (genus Dinovernavirus) were detected by culturing mosquito pools on Aedes albopictus (C6/36) cell cultures. A virus that caused overt cytopathic effects was isolated, but it did not infect vertebrate cells or produce detectable disease in infant mice after intracerebral inoculation. The virus, tentatively designated Fako virus (FAKV), represents the first 9-segment, double-stranded RNA (dsRNA) virus to be isolated in nature. FAKV appears to have a broad mosquito host range, and its detection in male specimens suggests mosquito-to-mosquito transmission in nature. The structure of the T‫1؍‬ FAKV virion, determined to subnanometer resolution by cryoelectron microscopy (cryo-EM), showed only four proteins per icosahedral asymmetric unit: a dimer of the major capsid protein, one turret protein, and one clamp protein. While all other turreted reoviruses of known structures have at least two copies of the clamp protein per asymmetric unit, FAKV's clamp protein bound at only one conformer of the major capsid protein. The FAKV capsid architecture and genome organization represent the most simplified reovirus described to date, and phylogenetic analysis suggests that it arose from a more complex ancestor by serial loss-of-function events. IMPORTANCEWe describe the detection, genetic, phenotypic, and structural characteristics of a novel Dinovernavirus species isolated from mosquitoes collected in Cameroon. The virus, tentatively designated Fako virus (FAKV), is related to both single-shelled and partially double-shelled viruses. The only other described virus in this genus was isolated from cultured mosquito cells. It was previously unclear whether the phenotypic characteristics of that virus were reflective of this genus in nature or were altered during serial passaging in the chronically infected cell line. FAKV is a naturally occurring single-shelled reovirus with a unique virion architecture that lacks several key structural elements thought to stabilize a single-shelled reovirus virion, suggesting what may be the minimal number of proteins needed to form a viable reovirus particle. FAKV evolved from more complex ancestors by losing a genome segment and several virion proteins. H uman and livestock diseases are commonly caused by viruses transmitted from enzootic hosts by arthropod vectors (1).Mosquito surveillance studies have been key to understanding the prevalence, distribution, and outbreak potential of the majority of these pathogens, as well as for the detection of novel pathogenic and nonpathogenic agents.The family Reoviridae consists of double-stranded RNA (dsRNA) viruses with 9 to 12 genome segments. Reoviruses have both a wide geographic distribution and wide host range, having been isolated from fungi, plants, insects, ticks, arachnids, fish, marine protists, crustaceans, mammals, and birds (2). They are divided into two ...

Insect-Specific Viruses

“…One study showed 100% TOT of Culex flavivirus (CxFV) by Culex pipiens (Saiyasombat et al, 2011). Other studies have also found evidence of TOT of ISVs both in lab mosquito colonies (Bolling et al, , 2012 and in field settings (Auguste et al, 2015;Cook, 2006;Farfan-Ale et al, 2010;Haddow et al, 2013;Sang et al, 2003). This TOT may be supplemented by additional transmission routes within the mosquito population.…”

“…Previous to the discovery of FAKV, the genus Dinovernavirus contained a single virus, Aedes pseudoscutellaris reovirus (APRV), which was isolated from the mosquito cell line AP61 (Attoui et al, 2005). FAKV was discovered in 2015 while screening pools of mosquitoes collected in Cameroon (Auguste et al, 2015). FAKV was found in both male and female mosquitoes, indicating vertical transmission in nature.…”

“…Fako virus (FAKV) is an insect-specific reovirus within the genus Dinovernavirus (Auguste et al, 2015). Previous to the discovery of FAKV, the genus Dinovernavirus contained a single virus, Aedes pseudoscutellaris reovirus (APRV), which was isolated from the mosquito cell line AP61 (Attoui et al, 2005).…”

“…have been repeatedly demonstrated to directly affect the ability of various species of mosquitoes to act as vectors for clinically important arboviruses including dengue (DENV), chikungunya (CHIKV), Zika (ZIKV), and West Nile (WNV) viruses (reviewed in Blagrove et al, 2012;Caragata et al, 2016;Dodson et al, 2014;Dutra et al 2016;Raquin et al, 2015). Wolbachia, however, is only a single bacterial genus of a multifaceted mosquito microbiome that is comprised of bacteria (Terenius et al, 2012), fungi (Bishop-Lilly et al, 2010), and viruses (Auguste et al, 2014(Auguste et al, , 2015Bolling et al, 2011;Cook et al, 2012;Hobson-Peters et al, 2016;Hoshino et al, 2009;Zuo et al, 2014). Indeed, this vast array of commensal organisms within the mosquito vector presents a potential avenue through which the vectors or the pathogens they transmit can be more effectively controlled (Lacey et al, 2015).…”

Fish reovirus GCReV-109 VP33 protein elicits protective immunity in rare minnows

“…Aquareoviruses, which belong to the family Reoviridae, can infect a variety of aquatic animals, including freshwater and marine fishes [1]. Aquareoviruses are non-enveloped and contain 11 segments (S1-S11) of linear double-stranded RNA [2], which encode seven structural proteins (VP1-VP7) and five nonstructural proteins [3].…”