Emerging orthobunyaviruses associated with CNS disease

Abstract

The Orthobunyavirus genus comprises a wide range of arthropod-borne viruses which are prevalent worldwide and commonly associated with central nervous system (CNS) disease in humans and other vertebrates. Several orthobunyaviruses have recently emerged and increasingly more will likely do so in the future. Despite this large number, an overview of these viruses is currently lacking, making it challenging to determine importance from a One Health perspective. Causality is a key feature of determining importance, yet classical tools are unfit to evaluate the causality of orthobunyaviral CNS disease. Therefore, we aimed to provide an overview of orthobunyaviral CNS disease in vertebrates and objectify the causality strength of each virus. In total, we identified 27 orthobunyaviruses described in literature to be associated with CNS disease. Ten were associated with disease in multiple host species of which seven included humans. Seven viruses were associated with both congenital and postnatal CNS disease. CNS disease-associated orthobunyaviruses were spread across all known Orthobunyavirus serogroups by phylogenetic analyses. Taken together, these results indicate that orthobunyaviruses may have a common tendency to infect the CNS of vertebrates. Next, we developed six tailor-made causality indicators and evaluated the causality strength of each of the identified orthobunyaviruses. Nine viruses had a ‘strong’ causality score and were deemed causal. Eight had a ‘moderate’ and ten a ‘weak’ causality score. Notably, there was a lack of case-control studies, which was only available for one virus. We, therefore, stress the importance of proper case-control studies as a fundamental aspect of proving causality. This comprehensible overview can be used to identify orthobunyaviruses which may be considered causal, reveal research gaps for viruses with moderate to low causality scores, and provide a framework to evaluate the causality of orthobunyaviruses that may newly emerge in the future.

Bat Flies of the Family Streblidae (Diptera: Hippoboscoidea) Host Relatives of Medically and Agriculturally Important “Bat-Associated” Viruses

“…In streblid bat flies from Uganda, we found mamucuso virus, a peribunyavirus in the genus Orthobunyavirus . Orthobunyaviruses are a large group of arboviruses with a worldwide and expanding distribution that cause severe central nervous system disease in vertebrates [ 42 , 43 , 44 ]. Mamucuso virus is part of a group of viruses associated with bats and their vectors ( Figure 5 ).…”

“…This clade is most closely related We identified three viruses in bat flies from Uganda (Table 1). Mamucuso virus (Peribunyaviridae: Orthobunyavirus) is a member of a genus containing vector-borne pathogens known to cause severe encephalitis in humans and other mammals (Figure 3) [42][43][44]. Within the orthobunyaviruses, mamucuso virus is part of a subclade of viruses from nycteribiid bat flies and louse flies (based on the L segment), also containing the mosquito-vectored human pathogen Nyando virus [42] (Figure 5).…”

The Cat Que Virus: a resurfacing orthobunyavirus could lead to epidemics

“…Recently, the International Committee on Taxonomy of Viruses (ICTV) updated that the species of orthobunyavirus. They found orthobunyavirus has been sharply increased in number (49 to 87) during 2011-2019 [5]. The increase in the numbers of viruses in the orthobunyavirus indicates their emerging potential due to their better adaptation capacity.…”

Orthobunyaviruses: From Virus Binding to Penetration into Mammalian Host Cells

“…For example, Oropouche virus (OROV) is the second most frequent cause of acute but self-limiting febrile illnesses in Central America [ 3 , 4 ]. Ngari virus is responsible for hemorrhagic fever in Africa [ 5 , 6 ], and La Crosse virus (LACV) is a common cause of pediatric encephalitis in North America [ 7 ]. In domestic animals, abortion, congenital malformations in offspring, and birth defects are frequently observed following infection by some OBVs.…”

“…Nothing is known about the viral penetration mechanism in arthropod cells, and hence, we limit our discussion here to the entry of OBVs into mammalian host cells. For information on OBVs and their arthropod vectors, we recommend reviewing [ 2 , 3 , 7 , 17 , 18 , 19 , 20 , 21 ].…”