Orthobunyaviruses: From Virus Binding to Penetration into Mammalian Host Cells

Abstract

With over 80 members worldwide, Orthobunyavirus is the largest genus in the Peribunyaviridae family. Orthobunyaviruses (OBVs) are arthropod-borne viruses that are structurally simple, with a trisegmented, negative-sense RNA genome and only four structural proteins. OBVs are potential agents of emerging and re-emerging diseases and overall represent a global threat to both public and veterinary health. The focus of this review is on the very first steps of OBV infection in mammalian hosts, from virus binding to penetration and release of the viral genome into the cytosol. Here, we address the most current knowledge and advances regarding OBV receptors, endocytosis, and fusion.

The La Crosse virus class II fusion glycoproteinijloop contributes to infectivity and cholesterol-dependent entry

“…Alphaviruses, flaviviruses and bunyaviruses all encode a class II fusion glycoprotein that play a vital role in mediating viral attachment and membrane fusion (7, 16, 17). However, while our understanding of alphavirus and flavivirus glycoprotein biology have grown significantly, our understanding of vector-borne bunyavirus glycoprotein function is less well understood.…”

“…Domain II of the class II fusion glycoproteins of alpha-, flavi-, and bunyaviruses contains the fusion loop (cd loop), the ij loop, and the bc loop. While the fusion loop of La Crosse has been studied extensively (7,(35)(36)(37), how the other loops function in virus entry has not been explored. In particular, the ij loop of alphaviruses and flaviviruses has been shown to be critical for virus assembly, entry, and transmission (19,24,26).…”

“…The Bunyavirales order includes a number of significant human pathogens such as Rift Valley fever virus, La Crosse virus, Oropouche virus, and Crimean Congo hemorrhagic fever virus (4, 5). La Crosse virus (LACV) is a member of the orthobunyavirus genus and is an enveloped segmented negative-strand RNA virus that contains a tripartite genome consisting of S, M, and L segments (6, 7). The S segment encodes for the nucleoprotein (N) and NSs protein (4, 8), the M segment encodes for the viral glycoproteins Gn and Gc (7, 9) and nonstructural protein NSm, and the L segment encodes for the viral RNA dependent RNA polymerase (4).…”

“…La Crosse virus (LACV) is a member of the orthobunyavirus genus and is an enveloped segmented negative-strand RNA virus that contains a tripartite genome consisting of S, M, and L segments (6, 7). The S segment encodes for the nucleoprotein (N) and NSs protein (4, 8), the M segment encodes for the viral glycoproteins Gn and Gc (7, 9) and nonstructural protein NSm, and the L segment encodes for the viral RNA dependent RNA polymerase (4). LACV is transmitted by the Aedes species of mosquito (10, 11) and can cause severe encephalitis, as it is the most common cause of pediatric neuroinvasive arboviral disease in children in the United States (12–15).…”

LINE-1 Retrotransposon-derived Proteins: The ORFull Truth?

“…As patients with mutations in the PURA gene continue to be identified, these findings expand our understanding of the functional domains of the PURA protein. Most recently a patient was described with a nonsense mutation within the PURA gene that expanded the range of phenotypes associated with PURA mutations to include short stature, problems with bone development and delayed puberty [36]. These studies do not immediately provide new information on how PURA might act at the molecular level or interact with L1-derived ORF1p.…”