Role of the NSs Protein in the Zoonotic Capacity of Orthobunyaviruses

Abstract

The family Bunyaviridae contains over 350 named isolates, classified into five genera: Orthobunyavirus, Hantavirus, Nairovirus, Phlebovirus and Tospovirus. The Orthobunyavirus genus contains some 170 isolates that are mainly transmitted by mosquitoes and are responsible for a range of disease syndromes in humans including self-limiting febrile illness, encephalitis and haemorrhagic fever. The viruses have a tripartite, negative-sense RNA genome. Analyses of viruses in four serogroups (Bunyamwera, California, Group C and Simbu) showed that the smallest (S) RNA segment encodes the nucleocapsid protein (N) and a non-structural protein called (NSs). The NSs protein of Bunyamwera virus (BUNV) has been shown to play a role in shut-off of host cell protein synthesis in mammalian cells, but no protein shut-off is observed in BUNVinfected mosquito cells (Aedes albopictus C6/36 cells). Protein shut-off in infected mammalian cells is achieved by global inhibition of RNA polymerase II-mediated transcription and enables the virus to overcome the host innate immune response. As innate defence mechanisms constitute a significant barrier to virus infection of different hosts, NSs would appear to play a key role in determining the zoonotic capacity of orthobunyaviruses.

Toscana Virus NSs Protein Inhibits the Induction of Type I Interferon by Interacting with RIG-I

“…This activity gives rise to the question of whether this viral protein has a proteolytic activity or if it activates a proteasome-mediated degradation pathway. Interestingly, NSs was scarcely expressed in HEK293FT cells upon plasmid transfection; however, treatment with MG-132 increased the level of protein, suggesting a protein-stabilizing effect of this drug, as already observed in orthobunyavirus NSs (7,41). The addition of MG-132 to the cells widely restored IFN-␤ promoter activation, suggesting that RIG-I degradation, mediated by NSs, was proteasome dependent and specific, since the nucleoprotein of TOSV did not show any of these effects.…”

Bunyavirus N: eIF4F surrogate and cap-guardian

“…Infection by members of the orthobunyavirus genus results in both transcriptional and translational shut off of host gene expression in mammalian cells. [37][38][39][40] Notably, translational abrogation of host expression is achieved by nuclear targeting or nuclear retention of PABP in the nucleus of infected cells. 41 N-mediated translation initiation would complement this virus-mediated shut off of host cell translation, and it is to be expected that N of the entire bunyavirus family facilitates translation initiation in a manner similar to that of hantavirus N. In the case of the hantaviruses, it is extremely unlikely that N-mediated translation initiation arose capriciously, without selection, and is without biological benefit for the virus.…”

Nuclear Relocalization of Polyadenylate Binding Protein during Rift Valley Fever Virus Infection Involves Expression of the NSs Gene

“…For BUNV, a small (11-kDa) NSs is encoded in an overlapping reading frame with N. For RVFV, ambisense coding produces a 31-kDa NSs. In addition, differing functions of the NSs proteins of orthobunyaviruses and phleboviruses have been identified in several studies (28,48,49). Consequently, it cannot be assumed that findings with BUNV also apply to bunyaviruses in other genera of the family, such as phleboviruses.…”