Bunyaviruses and Innate Immunity

Friedemann Weber; Richard M. Elliott

doi:10.1128/9781555815561.ch18

Chapter 18 : Bunyaviruses and Innate Immunity

Authors: Friedemann Weber¹, Richard M. Elliott²

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Affiliations: 1: Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79008 Freiburg, Germany; 2: Centre for Biomolecular Sciences, School of Biology, University of St. Andrews, St. Andrews, KY16 9ST, Scotland, United Kingdom

Content Type: Monograph

Publication Year: 2009

Category: Viruses and Viral Pathogenesis; Microbial Genetics and Molecular Biology

Book DOI: 10.1128/9781555815561

Chapter DOI: 10.1128/9781555815561.ch18

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Abstract:

This chapter summarizes the current state of knowledge about how the viruses of the Bunyaviridae succeed in establishing infection in the face of a powerful innate immune system. Members of the Bunyaviridae are classified into five genera: Orthobunyavirus, Phlebovirus, Hantavirus, Nairovirus, and Tospovirus. In this chapter the term ‘’bunyavirus‘’ refers to a member of the Bunyaviridae family, while the terms ‘’orthobunyavirus‘’ ‘’phlebovirus‘’ refer to viruses in the eponymous genus. A well-established animal model for pathogenicity of arthropod-transmitted bunyaviruses does exist for La Crosse virus (LACV) virus in mice. Just as it is described for crimean-Congo hemorrhagic fever virus (CCHFV), high levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are present in hantavirus patients. A similar scenario is conceivable for those bunyaviruses that use arthropods as vectors. The first interferon (IFN) antagonists described for bunyaviruses were the NSs proteins of the orthobunyavirus BUNV and the phlebovirus RVFV. Apparently, as bunyaviruses replicate in the cytoplasm and do not need ongoing cellular transcription for cap-snatching, blocking RNA polymerase II (RNAP II) function by NSs is the method of choice for orthobunyaviruses and phleboviruses to counteract innate immune responses. Despite the significant economic and medical impact of the huge RNA virus family, the interactions of bunyaviruses with the innate immune system are only incompletely understood. Thus, a better understanding of the interplay between bunyaviruses and the innate immune response, as with most other viruses, can help in the design of new strategies for prevention and therapy.

Citation: Weber F, Elliott R. 2009. Bunyaviruses and Innate Immunity, p 287-299. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch18

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Bunyaviruses and Innate Immunity

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Figure 1

Bunyamwera orthobunyavirus coding strategy (not to scale). The three genomic RNA segments L, M, and S are shown as solid lines with their lengths in nucleotides (nt) shown above. mRNAs are indicated by arrows, with boxes depicting a nontemplated primer at the 5′ end. Gene products are shown as hatched boxes, and protein designations and sizes (kDa) are indicated.

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Figure 1

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Figure 2

Bunyavirus transcription and replication. (A) Negative-sense bunyavirus genome segments. The genome RNA and the positive-sense complementary RNA known as the antigenome RNA are only found as ribonucleoprotein complexes and are encapsidated by N protein (•). The mRNA species contain host-derived primer sequences at their 5′ ends (•) and are truncated at the 3′ end relative to the viral RNA template; the mRNAs are not polyadenylated, nor are they encapsidated by N protein. The sequence at the 5′ end of an orthobunyavirus mRNA is shown. (B) Ambisense-sense bunyavirus genome segments. The genome RNA encodes proteins in both negative- and positive-sense orientations, separated by an intergenic region that can form a hairpin structure. The proteins are translated from subgenomic mRNAs, with the mRNA encoding protein 2 transcribed from the antigenome RNA after the onset of genome replication.

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Figure 2

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Figure 3

Prime-and-realign model for initiation of hantavirus genome synthesis. The template RNA is shown as the top strand with the 3′ nucleotide circled. Genome synthesis is initiated with GTP that aligns with the C residue at position 3 of the template. Following elongation of a few nucleotides, the nascent genomic strand realigns on the template by backwards slippage over the conserved sequence in the template. The initiating, now overhanging, GTP is then cleaved from the nascent strand, leaving a monophosphorylated U as the 5′ nucleotide in the genomic RNA. (Redrawn from reference 38 .)

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Figure 3

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Tables

Bunyaviruses and Innate Immunity

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Table 1

Consensus 3′ and 5′ terminal nucleotide sequences of bunyaviral genome RNAs

Table 1

Consensus 3′ and 5′ terminal nucleotide sequences of bunyaviral genome RNAs

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Table 2

Selected important pathogens in the family Bunyaviridae

Table 2

Selected important pathogens in the family Bunyaviridae