Abstract
The genus Orthobunyavirus (family Peribunyaviridae, order Bunyavirales) comprises over 170 named mosquito- and midge-borne viruses, several of which cause severe disease in animals or humans. Their three-segmented genomes enable reassortment with related viruses, which may result in novel viruses with altered host or tissue tropism and virulence. One such reassortant, Schmallenberg virus (SBV), emerged in north-western Europe in 2011. Shuni virus (SHUV) is an orthobunyavirus related to SBV that is associated with neurological disease in horses in southern Africa and recently caused an outbreak manifesting with neurological disease and birth defects among ruminants in Israel. The zoonotic potential of SHUV was recently underscored by its association with neurological disease in humans. We here report a reverse genetics system for SHUV and provide first evidence that the non-structural (NSs) protein of SHUV functions as an antagonist of host innate immune responses. We furthermore report the rescue of a reassortant containing the L and S segments of SBV and the M segment of SHUV. This novel reverse genetics system can now be used to study SHUV virulence and tropism, and to elucidate the molecular mechanisms that drive reassortment events.
Highlights
The genus Orthobunyavirus is the largest genus within the order Bunyavirales, comprising over 170 named arthropod-borne viruses divided over 18 serogroups [1,2]
We report a reverse genetics system that can be used to study Shuni virus (SHUV) virulence and tropism
In agreement with studies previously performed with Schmallenberg virus (SBV) lacking NSs, both rSBV∆NSs and rSHUV∆NSs were significantly attenuated in IFN-competent cells, attributed to the IFN antagonistic function of orthobunyavirus NSs proteins [11,12]
Summary
The genus Orthobunyavirus (family Peribunyaviridae) is the largest genus within the order Bunyavirales, comprising over 170 named arthropod-borne (arbo) viruses divided over 18 serogroups [1,2]. Apart from veterinary pathogens, the genus Orthobunyavirus, comprises human pathogens, such as Oropouche virus (OROV), which causes a mild, self-limiting febrile illness [6,7]. Orthobunyaviruses causing more severe human disease include LaCrosse virus (LACV), the leading cause of pediatric arboviral encephalitis in the US, and Ngari virus, which was associated with large outbreaks of haemorrhagic fever in Africa [8,9]. Orthobunyaviruses contain a negative-strand RNA genome that is divided into three segments, named after their size, large (L), medium (M), and small (S) [2].
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